Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Medical management includes ursodeoxycholic acid as the 1st-line treatment and for symptom management. Definitive treatment is liver transplantation, which is performed in late stages (cirrhosis).
Highest prevalencePrevalenceThe total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time.Measures of Disease Frequency in Europe and North America
Most commonly diagnosed in 4th–6th decades of life
Primary biliary cholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis (PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis) accounts for < 1% of liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplantations in the US.
Etiology
There is a presumed autoimmune etiology.
Associated with:[6]
Sjögren’s syndrome
SclerodermaSclerodermaScleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma
CREST (calcinosisCalcinosisPathologic deposition of calcium salts in tissues.Scleroderma, Raynaud’s phenomenon, esophageal dysmotilityEsophageal DysmotilityScleroderma, sclerodactylySclerodactylyScleroderma, and telangiectasiaTelangiectasiaPermanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.Chronic Venous Insufficiency) syndrome
Hashimoto’s thyroiditisThyroiditisThyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis
Combined genetic risk and environmental triggers (which include urinary tractUrinary tractThe urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra.Urinary Tract: AnatomyinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease, smokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases, reproductive hormone replacement, and nail polish)[6,16,19]
Pathophysiology
The exact mechanism is not known.
Chronic, progressive liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease: autoimmune destruction and/or inflammationof intrahepatic bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts → cholestasis (impaired bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy production and flowFlowBlood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls.Vascular Resistance, Flow, and Mean Arterial Pressure) → gradual portal and periportal fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans → liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomycirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and portal hypertensionPortal hypertensionPortal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension → liver failureLiver failureSevere inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio.Autoimmune Hepatitis[16,17,19,20]
Pathophysiology of primary biliary cholangitis (PBC):
A risk factor or trigger may lead to a coordinated T and B cell-mediated response, resulting in biliary epithelial cell (BEC) injury, cholestasis, and fibrosis.
Primary biliary cholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis has a wide range of symptoms. The condition is often asymptomatic in the early phase and features symptoms of decompensated cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis in the late phaseLate PhaseSepsis in Children.
It takes about 2–4 years for disease manifestations to be noticed in asymptomatic patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.[1,20]
Acute presentation:
PruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema):[1]
Seen in 70%
Declining presentation due to early diagnosis (when patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship are still asymptomatic)
Aggravated by heatHeatInflammation, contact with clothing, pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care, estrogenEstrogenCompounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.Ovaries: Anatomy (hormone replacement, oral contraceptives)[6]
Worse at night
Cholestasis → believed to ↑ lysophosphatidic acid, bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: AnatomyacidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance, and endogenous opioidsOpioidsOpiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics (mediators of pruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema))
FatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia:[6]
Most common
Seen in up to 78% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
Chronic presentation:
Hepatomegaly +/– splenomegalySplenomegalySplenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
JaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
MelanosisMelanosisDisorders of increased melanin pigmentation that develop without preceding inflammatory disease.Primary Biliary Cholangitis (darkening skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions)
XanthomasXanthomasLipid Disorders (fatty cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism deposits underneath the skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions) and xanthelasmaXanthelasmaPrimary Biliary Cholangitis (xanthomasXanthomasLipid Disorders around the eyelidsEyelidsEach of the upper and lower folds of skin which cover the eye when closed.Blepharitis)
Hepatocellular failure (cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
Portal hypertensionPortal hypertensionPortal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension (ascitesAscitesAscites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection).Ascites, variceal bleeding, etcETCThe electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP).Electron Transport Chain (ETC).)
↑ Risk of hepatocellular carcinomaHepatocellular carcinomaHepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases[19]
High incidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency of osteoporosisOsteoporosisOsteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis due to vitamin D deficiencyVitamin D DeficiencyA nutritional condition produced by a deficiency of vitamin D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as rickets in children and osteomalacia in adults.Fat-soluble Vitamins and their Deficiencies[18]
PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis can overlap with autoimmune hepatitisAutoimmune hepatitisAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis (AIHAIHAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis): associated with more complications (portal hypertensionPortal hypertensionPortal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension)[6]
Jaundice: yellow discoloration of the skin due to bilirubin deposition
Image: “Jaundice08” by James Heilman, MD. License: CC BY 3.0
Diagnosis
There may be variations in practice based on location. Review detailed recommendations for different regions (US, UK, Europe).
TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis: aspartateAspartateOne of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.Synthesis of Nonessential Amino Acids aminotransferase (ASTASTEnzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate.Liver Function Tests) and alanineAlanineA non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system.Synthesis of Nonessential Amino Acids aminotransferase (ALTALTAn enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate.Liver Function Tests) are slightly ↑
↑ Alkaline phosphataseAlkaline PhosphataseAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma (ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma)
↑ Conjugated bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism
↑ Gamma-glutamyltransferaseGamma-glutamyltransferaseAn enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Liver Function Tests (GGTGGTAn enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Alcoholic Liver Disease)
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomybiopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma:
Not required → but can confirm the diagnosis[16,19]
More useful for stagingStagingMethods which attempt to express in replicable terms the extent of the neoplasm in the patient.Grading, Staging, and Metastasis (prognostic indicatorIndicatorMethods for assessing flow through a system by injection of a known quantity of an indicator, such as a dye, radionuclide, or chilled liquid, into the system and monitoring its concentration over time at a specific point in the system.Body Fluid Compartments)
Also performed when treatment response is inadequate[20]
Characteristic findings:
Early finding of chronic, nonsuppurative inflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation surrounding interlobular and septal bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts (florid duct lesion)[6,20]
Eventually, ductopenia and collagenCollagenA polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth).Connective Tissue: Histology deposition follow.[20]
If AIHAIHAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis is suggested by tests (↑ ALTALTAn enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate.Liver Function Tests, anti–smooth-muscle antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions), proceed with biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma.[6,16,19]
Imaging:
RUQ ultrasonography (US):[6,16,20]
Visualizes the liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and biliary treeBiliary treeThe bile ducts and the gallbladder.Gallbladder and Biliary Tract: Anatomy to evaluate cause of cholestasis
Excludes alternative diagnoses
Needed as a baseline study for those with suspected PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis
Magnetic resonance cholangiopancreatographyMagnetic resonance cholangiopancreatographyNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis (MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis) and endoscopic ultrasonography (EUS):
In some cases, MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis is needed to exclude primary sclerosing cholangitisPrimary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis and other extrahepatic causes of cholestasis.[6,19,20]
EUS is an alternative test for evaluating distal biliary disease.[20]
Vibration-controlled transient elastography:[17]
Not needed for diagnosis, but used in further evaluation
Noninvasive technique (US) that checks for fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans (liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy stiffness)
Determining level of fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans affects the prognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas and management options.
Table: Histologic stages of PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis[6]
Stage
Histologic findings
Stage 0
Normal
Stage I
Portal inflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation +/– florid bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy duct lesions (inflammatory changes and necrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage surrounding bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts)
InflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation limited to portal triads
Distorted liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy structure with ↑ fibrousFibrousFibrocystic Change septa (bridging fibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans)
Stage IV
CirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, with regenerative nodules
Primary biliary cirrhosis, demonstrating chronic nonsuppurative destructive cholangitis: Infiltration of lymphocyte (arrow) and plasma cell (bold arrow) into the bile duct is shown.
Image: “Primary biliary cirrhosis” by Department of Medicine, Toronto Western Hospital (University Health Network/University of Toronto), Toronto, Ontario, Canada. License: CC BY 2.0
Diagnostic approach
In ordering tests for suspected PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis and for monitoring PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis, it is important to take note of the pathophysiologic processes that take place.[17]
Autoimmune destruction and inflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions (e.g., AMAAMAPrimary Biliary Cholangitis)
Cholestasis → hepatic panel (e.g., abnormal ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma)
FibrosisFibrosisAny pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Bronchiolitis Obliterans → consider histopathology or imaging
Criteria:[6,16]
No extrahepatic biliary obstruction
No hepatic comorbiditiesComorbiditiesThe presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.St. Louis Encephalitis Virus
2 of the following:
ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma ≥ 1.5 the upper limitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation of normal
Histologic changes of PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis (chronic nonsuppurative cholangitis affecting the interlobular and septal bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts, interlobular ductInterlobular DuctPrimary Sclerosing Cholangitis obstruction)
PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis/AIHAIHAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis overlap:[6]
Paris criteria (meets 2 of 3 criteria):
Serum alanineAlanineA non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system.Synthesis of Nonessential Amino Acids aminotransferase level ≥ 5 times the upper limitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation of normal
Immunoglobulin (IgIgX-linked Agammaglobulinemia) G level ≥ 2 times the upper limitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation of normal and/or positive for smooth muscle antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions
1st-line agent: ursodeoxycholic acidUrsodeoxycholic acidAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis (UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis, ursodiolUrsodiolAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis)
Up to 40% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship do not respond.
CholestyramineCholestyramineA strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion.Lipid Control Drugs may be used for pruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema) and hypercholesterolemiaHypercholesterolemiaA condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Lipid Disorders.
CalciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes and vitamin DVitamin DA vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone.Fat-soluble Vitamins and their Deficiencies supplementation for low boneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types density
BisphosphonatesBisphosphonatesBisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption.Bisphosphonates given for severe osteoporosisOsteoporosisOsteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
Details of therapy
Goals:[6,16]
Suppress the destruction of intralobular bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts.
Decrease and treat the associated symptoms.
Reduce and manage the complications of the disease.
Pretreatment measures:[6,7]
Update immunizations (hepatitis AHepatitis AHepatitis A is caused by the hepatitis A virus (HAV), a nonenveloped virus of the Picornaviridae family with single-stranded RNA. HAV causes an acute, highly contagious hepatitis with unspecific prodromal symptoms such as fever and malaise followed by jaundice and elevated liver transaminases. Hepatitis A Virus and B)
Abstinence from, or cessation of, alcohol intake
Maintain ideal body weight or reduce weight if obese
Consultation with a liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy specialist
Baseline laboratory tests
Specific therapy:
UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis:[6,16,20]
1st-line therapy (lifelong)
Oral, given at 13–15 mg/kg twice daily (initiate gradually)
Improvement in liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biochemical tests noted in about 3 months, with ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma normalization in 1 year
Those with earlier stages have more favorable responses.
↓ Need for transplantation; slows histologic progression
Added benefits:
↓ LDL cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism
Oral, initially given at 5 mg/day (maximum dose: 10 mg/day)
Potent farnesoid X receptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors (FXR) agonist (modulating bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy acid synthesisSynthesisPolymerase Chain Reaction (PCR) and metabolism)
Uses:
Can be added for patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with inadequate response to UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis (ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma did not normalize in 1 year).
Can also be monotherapy if UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis is not tolerated
Improvement in liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biochemical tests (ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma ≤ 1.67 times upper limitLimitA value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lungInvasive Mechanical Ventilation of normal) noted in about 6 months
Contraindicated in advanced cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis (avoid in those with previous or current decompensation (e.g., encephalopathyEncephalopathyHyper-IgM Syndrome, varices) or portal hypertensionPortal hypertensionPortal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension)
FenofibrateFenofibrateAn antilipemic agent which reduces both cholesterol and triglycerides in the blood.Lipid Control Drugs 160 mg/day
Bezafibrate 400 mg/day (not available in the United States)
Off-label therapy added to UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis if there is inadequate response to UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis
Contraindicated in decompensated liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
Symptom treatment:
FatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia:[6]
Etiology is multifactorial.
No specific drug therapy
PruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema):
Avoid tight clothing, use skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions moisturizers, avoid hot baths[6]
1st-line: anion exchange resins[6,16,20]
CholestyramineCholestyramineA strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion.Lipid Control Drugs (4‒16 g/day)
Administered 2–4 hours before or after UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis (can interfere with UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary CholangitisabsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption)
2nd-line: rifampinRifampinA semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms.Epiglottitis 150‒300 mg/day[16]
Opiate antagonists:
IV naloxoneNaloxoneA specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Opioid Analgesics: bolus of 0.4 mg, then 0.2 µg/kg/min for 24 hours in the hospital[6,8]
Oral nalmefene: 60‒120 mg/day[9,20]
Oral naltrexoneNaltrexoneDerivative of noroxymorphone that is the n-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction.Opioid Analgesics: 12.5‒50 mg daily[6,20]
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines help because of their sedative effects (itching is not histamine-related).[6,20]
Dry eyes and dry mouth (sicca syndromeSicca syndromeSjögren syndrome (SS) is an autoimmune, inflammatory condition where glandular tissues, such as the salivary and lacrimal glands, are infiltrated by lymphocytes, resulting in decreased tear and saliva production.Sjögren Syndrome):[6]
For keratoconjunctivitisKeratoconjunctivitisSimultaneous inflammation of the cornea and conjunctiva.Stevens-Johnson Syndrome, use hydroxypropyl methylcelluloseMethylcelluloseMethylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative.Laxatives or carboxymethylcellulose moisturizing eye drops as needed.
For severe eye symptoms, consult an eye specialist to consider immunosuppressive drugsImmunosuppressive drugsAgents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging.Organ Transplantation such as cyclosporineCyclosporineA cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation.Immunosuppressants.
For dry mouth, regularRegularInsulin dental cleaning and checkups are recommended.
Sugar-free gum, salivaSalivaThe clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin.Salivary Glands: Anatomy substitutes, and sips of water also improve salivaSalivaThe clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin.Salivary Glands: Anatomy production.
More severe oral symptoms may benefit from cholinergic agents (pilocarpinePilocarpineA slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.Cholinomimetic Drugs, cevimeline), but these have adverse effects.
For boneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types protection:[16,19]
Daily calciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes (1500 mg/day) and vitamin DVitamin DA vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone.Fat-soluble Vitamins and their Deficiencies supplements (1000 IU/day)
BisphosphonatesBisphosphonatesBisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption.Bisphosphonates (e.g., alendronateAlendronateA nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.Bisphosphonates 70 mg weekly, ibandronate 150 mg monthly) for osteoporosisOsteoporosisOsteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
Hyperlipidemia:
UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis helps lower LDL cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism.
Consider statinsStatinsStatins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides.Statins for those at risk for cardiovascular disease following American College of Cardiology guidelines (calculator).
In advanced disease, individualized consideration for vitamin AVitamin ARetinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products.Fat-soluble Vitamins and their Deficiencies, D, E, and K supplementation is recommended.[16,20]
PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with end-stage PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis with Model for End-stage LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy Disease (MELD) score ≥ 15[6] (in UK, UKELD ≥ 49)[16] → refer for transplantation
Other indications:
Total bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism ≥ 6 mg/dL[6] or progressive increase of bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism 3–5 mg/dL (50–85 µmol/L)[20]
In some cases of refractory pruritus[6,16,20]
Not all symptoms improve with transplantation:
PruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema) improves, but sicca symptoms persist.
FatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia continues in about 50%.[6]
PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis can recur after transplantation (average, 20%).[10,16,20]
UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis is given in those with recurrence.[20]
PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis/AIHAIHAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis overlap:[19]
If biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma confirms diagnosis, give corticosteroidsCorticosteroidsChorioretinitis with UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis
Immunosuppressive therapy (e.g., azathioprineAzathioprineAn immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen.Immunosuppressants) is also given (eventually as a steroid-sparing agent) to maintain remissionRemissionA spontaneous diminution or abatement of a disease over time, without formal treatment.Cluster Headaches.
Follow-up and prognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas
Follow-up:
Monitor laboratory test results:[6,20]
Aminotransferases, ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma, GGTGGTAn enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Alcoholic Liver Disease, bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism, platelet count) every 3–6 months
Fat-soluble vitamins A, D, and E (especially in those with jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice or bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism > 2 mg/dL) yearly
PT/INR yearly
TSH yearly
Imaging studies and hepatocellular screeningScreeningPreoperative Care (in men and in those with cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis):[6]
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy ultrasonography every 6 months
Monitor cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and complications:
Upper endoscopyEndoscopyProcedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body.Gastroesophageal Reflux Disease (GERD) (to screen for varices) in those with cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, with interval follow-up dependent on initial findings.[6,16]
Transient elastography (obtain baseline study) to check liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy stiffness[16,20]
BoneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineral densitometry every 2 years[6,19]
Early diagnosis and treatment with UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis lead to a favorable prognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas.[20]
Factors associated with worse prognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas:
Elevated ALPALPAn enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate.Osteosarcoma and bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism[11]
ANA-positive[12]
Advanced histologic stage[13,20]
SmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases[14]
Genetic polymorphisms (genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure involved in immunity, cytotoxicCytotoxicParvovirus B19 T-lymphocyte–associated antigen-4 (CTLA-4) and tumorTumorInflammationnecrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage factor 4 (TNF-alpha) are associated with susceptibility to PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis[15]
Differential Diagnosis
Primary biliary cholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis should be differentiated from primary sclerosing cholangitisPrimary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis (PSCPSCPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis), because the 2 conditions have similar presentations.
Table: Primary sclerosing cholangitisPrimary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis compared to primary biliary cholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis
PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis
PSCPSCPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis
Predominantly women
Predominantly men
Associated with autoimmune diseasesAutoimmune diseasesDisorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Selective IgA Deficiency
Associated with IBD
Intrahepatic involvement only
Intra- and extrahepatic involvement
Absence of bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy duct narrowing on MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis
MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis shows narrowing and dilation of bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts.
Primary sclerosing cholangitisPrimary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis: an inflammatory disease of the bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts that causes narrowing of the biliary treeBiliary treeThe bile ducts and the gallbladder.Gallbladder and Biliary Tract: Anatomy due to scarringScarringInflammation. Associated with ulcerative colitisColitisInflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever.Pseudomembranous Colitis. PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship present with fatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia, pruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema), and icterusIcterusA clinical manifestation of hyperbilirubinemia, characterized by the yellowish staining of the skin, mucous membranes, and sclera. Clinical jaundice usually is a sign of liver dysfunction.Jaundice. Diagnosis is by MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis (magnetic resonance cholangiopancreatographyMagnetic resonance cholangiopancreatographyNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis) and management is symptomatic. Definitive treatment is liver transplantationLiver transplantationThe transference of a part of or an entire liver from one human or animal to another.Hepatocellular Carcinoma (HCC) and Liver Metastases in late stages (cirrhosisCirrhosisCirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis).
BileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy duct obstruction: an obstruction of the biliary system that also presents with jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice and increased cholestasis laboratories. The acute onset of jaundiceJaundiceJaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, right upper quadrantRight upper quadrantAnterior Abdominal Wall: AnatomypainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways, and a higher elevation of aminotransferases help differentiate the condition from PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis. Further differentiation can be made by ultrasound or MRCPMRCPNon-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities.Primary Sclerosing Cholangitis. Biliary obstructions have many causes, including gallstonesGallstonesCholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant).Cholelithiasis and tumors. Treatment is based on etiology.
Autoimmune hepatitisAutoimmune hepatitisAutoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain).Autoimmune Hepatitis:liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomyinflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation that occurs when the body’s immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs turns against liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cells. Clinical presentation ranges from asymptomatic to symptoms of acute liver failureLiver failureSevere inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio.Autoimmune Hepatitis. Diagnosed by testing for serum anti-smooth muscle antibodiesAntibodiesImmunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution.Immunoglobulins: Types and Functions and liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomybiopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma. Treatment is with corticosteroidsCorticosteroidsChorioretinitis and azathioprineAzathioprineAn immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen.Immunosuppressants. With early treatment, the prognosisPrognosisA prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations.Non-Hodgkin Lymphomas is favorable. If left untreated, half of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship die in the first few years.
Billing and Coding
Diagnosis Codes: This code is used to diagnose Primary Biliary CholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis (PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis), a chronic, progressive autoimmune disease that causes destruction of the small bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy ducts within the liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.
Coding System
Code
Description
ICD-10-CM
K74.3
Primary biliary cirrhosisBiliary cirrhosisFibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.Cystic Fibrosis
SNOMED CT
235882004
Primary biliary cholangitisPrimary Biliary CholangitisPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis (disorder)
Evaluation & Workup: This CPT code is for testing for antimitochondrial antibodiesAntimitochondrial AntibodiesPrimary Biliary Cholangitis (AMAAMAPrimary Biliary Cholangitis), a highly specific serologic marker for PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis and a key component of its diagnosis.
Medications: This code is for ursodeoxycholic acidUrsodeoxycholic acidAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis (UDCAUDCAAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis), the primary medical therapy for PBCPBCPrimary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis.Primary Biliary Cholangitis, which helps improve bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: AnatomyflowFlowBlood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls.Vascular Resistance, Flow, and Mean Arterial Pressure and liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function, slowing the progression of the disease.
Coding System
Code
Description
RxNorm
11158
UrsodiolUrsodiolAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis (ingredient)
ATC
A05AA02
Ursodeoxycholic acidUrsodeoxycholic acidAn epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Primary Biliary Cholangitis
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