Evaluation of abnormal liver function tests (LFTs)

Autoimmune hepatitis is a chronic inflammatory hepatitis, four times more common in women, marked by elevated aminotransferases, autoantibodies, and hypergammaglobulinemia, confirmed by liver biopsy after excluding other causes. Treatment is immunosuppression with prednisone, usually combined with azathioprine, continued for at least 2 to 3 years before withdrawal is considered.

Primary biliary cholangitis is an autoimmune, T cell-mediated destruction of small and medium intrahepatic bile ducts that presents with fatigue and pruritus in middle-aged women and a cholestatic liver chemistry pattern. Diagnosis requires two of three criteria (elevated alkaline phosphatase, positive antimitochondrial antibody, compatible biopsy), and lifelong ursodeoxycholic acid is first-line treatment, with obeticholic acid or fibrates added for inadequate biochemical response.

Primary sclerosing cholangitis is an autoimmune fibroinflammatory disease of the large bile ducts, occurring mostly in young men and associated with inflammatory bowel disease, chiefly ulcerative colitis, in 80 to 90% of cases. MRCP showing multifocal strictures and dilations confirms the diagnosis, no drug alters progression, and management centers on endoscopic dilation of dominant strictures, surveillance for cholangiocarcinoma and colorectal cancer, and liver transplantation for advanced disease.

MASLD (formerly NAFLD) is hepatic steatosis with at least one cardiometabolic risk factor after exclusion of significant alcohol use and other liver disease, and a subset progresses to steatohepatitis (MASH, formerly NASH) with inflammation and fibrosis. Diagnosis rests on imaging-confirmed steatosis plus noninvasive fibrosis risk stratification, and management centers on 7% to 10% weight loss with aggressive treatment of diabetes and dyslipidemia.

Hepatitis A virus is a fecal-oral RNA virus that causes acute, host-immune-mediated hepatitis with a prodrome followed by jaundice, aminotransferases often exceeding 1,000 U/L, and full recovery in at least 90% of patients within 3 to 6 months. Diagnosis rests on HAV IgM, treatment is supportive, and prevention centers on a 2-dose inactivated vaccine plus prompt postexposure prophylaxis.

Hepatitis B virus is a bloodborne and sexually transmitted DNA virus that causes acute hepatitis and, when infection becomes chronic, progresses through immune-tolerant, immune-active, immune-control, and reactivation phases toward cirrhosis and hepatocellular carcinoma. Diagnosis rests on hepatitis B serology, chronic infection is treated with entecavir or tenofovir, and reactivation during immunosuppression is prevented with prophylactic antiviral therapy.

Hepatitis C virus is a bloodborne RNA virus, transmitted mainly by injection drug use, that produces mostly asymptomatic acute infection and chronic infection in 60% to 80% of cases. Diagnosis is by HCV antibody followed by HCV RNA, and direct-acting antiviral regimens cure more than 90% of patients, reducing but not eliminating the risk of cirrhosis and hepatocellular carcinoma.

Hemochromatosis is a disorder of iron overload, most often hereditary HFE C282Y homozygosity causing hepcidin deficiency and excess intestinal iron absorption, that deposits iron in the liver, pancreas, heart, joints, skin, and pituitary. Screening rests on fasting transferrin saturation and ferritin, confirmation on HFE genetic testing, and treatment on regular therapeutic phlebotomy to a target ferritin of 50 to 100 ng/mL.

Wilson disease is an autosomal recessive disorder of the ATP7B copper-transporting ATPase causing toxic copper accumulation in the liver, brain, and cornea, presenting with hepatic and/or neuropsychiatric disease usually before age 40; diagnosis rests on ceruloplasmin, urinary copper, and Kayser-Fleischer rings, and lifelong treatment is chelation with penicillamine or trientine, or zinc, unless liver transplant is required.