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Without liver transplantation, survival averages 7 10 years once symptoms develop Progression to liver failure and portal hypertension is associated with the presence of antigp210 and anticentromere antibodies, respectively, and may be accelerated by smoking In advanced disease, adverse prognostic markers are older age, high serum bilirubin, edema, low serum albumin, prolonged prothrombin time, and variceal hemorrhage Fatigue is associated with an increased risk of cardiac mortality Among asymptomatic patients, at least one-third will become symptomatic within 15 years The risk of hepatobiliary malignancies appears to be increased in patients with primary biliary cirrhosis Liver transplantation for advanced primary biliary cirrhosis is associated with a 1-year survival rate of 85 90% The disease recurs in the graft in 20% of patients by 3 years, but this does not seem to affect survival
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Kaplan MM et al Primary biliary cirrhosis N Engl J Med 2005 Sep 22;353(12):1261 73 [PMID: 16177252] Shi J et al Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials Am J Gastroenterol 2006 Jul;101(7):1529 38 [PMID: 16863557] Wesierska-Gadek J et al Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis Hepatology 2006 May;43(5):1135 44 [PMID: 16628641] Zein CO et al Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: a cross validated retrospective assessment Hepatology 2006 Dec;44(6):1564 71 [PMID: 17133468]
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HEMOCHROMATOSIS
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The onset of clinical disease is usually after age 50 years earlier in men than in women; however, because of widespread liver biochemical testing and iron screening, the diagnosis can be made long before symptoms develop
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ESSENTIALS OF DIAGNOSIS
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Usually diagnosed because of elevated iron saturation or serum ferritin or a family history
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measurement of the transferrin saturation or perhaps the unbound iron-binding capacity has been recommended by some experts, but the value of screening has been questioned because morbidity and mortality from hemochromatosis are low Patients with otherwise unexplained chronic liver disease, arthritis, impotence, and late-onset type 1 (and possibly type 2) diabetes mellitus should be screened for iron overload
Early symptoms are nonspecific (eg, fatigue, arthralgias) Later clinical manifestations include arthropathy, hepatomegaly and evidence of hepatic insufficiency (late finding), skin pigmentation (combination of slate-gray due to iron and brown due to melanin, sometimes resulting in bronze color), cardiac enlargement with or without heart failure or conduction defects, diabetes mellitus with its complications, and impotence in men Interestingly, population studies have shown an increased prevalence of liver disease but not of diabetes, arthritis, or heart disease in C282Y homozygotes Bleeding from esophageal varices may occur, and in patients in whom cirrhosis develops, there is a 15 20% frequency of hepatocellular carcinoma Affected patients are at increased risk of infection with Vibrio vulnificus, Listeria monocytogenes, Yersinia enterocolitica, and other siderophilic organisms
Treatment
Affected patients should avoid foods rich in iron (such as red meat), alcohol, vitamin C, raw shellfish, and supplemental iron Weekly phlebotomies of 1 or 2 units (250 500 mL) of blood (each containing about 250 mg of iron) is indicated in all symptomatic patients, those with a serum ferritin level of at least 1000 mcg/L, and those with an increased fasting iron saturation and should be continued for up to 2 3 years to achieve depletion of iron stores The hematocrit and serum iron values should be monitored When iron store depletion is achieved (iron saturation < 50% and serum ferritin level < 50 mcg/L), maintenance phlebotomies (every 2 4 months) are continued (although compliance has been reported to decrease with time) The chelating agent deferoxamine is indicated for patients with hemochromatosis and anemia or in those with secondary iron overload due to thalassemia who cannot tolerate phlebotomies The drug is administered intravenously or subcutaneously in a dose of 20 40 mg/kg/d infused over 24 hours and can mobilize 30 mg of iron per day However, treatment is painful and time-consuming An oral chelator, deferasirox, 20 mg/kg once daily, has been approved for treatment of iron overload due to blood transfusions Complications of hemochromatosis arthropathy, diabetes, heart disease, portal hypertension, and hypopituitarism also require treatment The course of the disease is favorably altered by phlebotomy therapy Fibrosis may regress, and in precirrhotic patients, cirrhosis may be prevented Cardiac conduction defects and insulin requirements improve with treatment In patients with cirrhosis, varices may reverse, and the risk of variceal bleeding declines, although the risk of hepatocellular carcinoma persists Liver transplantation for advanced cirrhosis associated with severe iron overload, including hemochromatosis, has been reported to lead to survival rates that are lower than those for other types of liver disease because of cardiac complications and an increased risk of infections
Adams PC Review article: the modern diagnosis and management of haemochromatosis Aliment Pharmacol Ther 2006 Jun 15;23(12):1681 91 [PMID: 16817911] Falize L et al Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases Hepatology 2006 Aug; 44(2):472 7 [PMID: 16871557] Walsh A et al The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis Clin Gastroenterol Hepatol 2006 Nov;4(11):1403 10 [PMID: 16979952] Whitlock EP et al Screening for hereditary hemochromatosis: a systematic review for the US Preventive Services Task Force Ann Intern Med 2006 Aug 1;145(3):209 23 [PMID: 16880463]
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