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Dig Dis Sci. 2013 Jun;58(6):1459-76. doi: 10.1007/s10620-012-2525-5. Epub 2013 Jan 10.

Hepatocellular carcinoma and other malignancies in autoimmune hepatitis.

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  • 1Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.


Hepatocellular carcinoma and extrahepatic malignancies can complicate the course of autoimmune hepatitis, and these occurrences may increase in frequency as the survival of patients with cirrhosis is extended and the prospect of new nonstandard immune-modifying intervention is realized. The frequency of hepatocellular carcinoma in patients with autoimmune hepatitis and cirrhosis is 1-9 %, and annual occurrence in patients with cirrhosis is 1.1-1.9 %. The standardized incidence ratio for hepatocellular carcinoma in autoimmune hepatitis is 23.3 (95 % confidence interval (CI) 7.5-54.3) in Sweden, and the standardized mortality ratio for hepatobiliary cancer is 42.3 (95 % CI 20.3-77.9) in New Zealand. The principal risk factor is long-standing cirrhosis, and patients at risk are characterized mainly by cirrhosis for ≥ 10 years, manifestations of portal hypertension, persistent liver inflammation, and immunosuppressive therapy for ≥ 3 years. Multiple molecular disturbances, including the accumulation of senescent hepatocytes because of telomere shortening, step-wise accumulation of chromosomal injuries, and aberrations in transcription factors and genes, may contribute to the risk. Extraheptic malignancies of diverse cell types occur in 5 % in an unpredictable fashion. The standardized incidence ratio is 2.7 (95 % CI 1.8-3.9) in New Zealand, and non-melanoma skin cancers are most common. Outcomes are related to the nature and stage of the tumor at diagnosis. Surveillance recommendations have not been promulgated, but hepatic ultrasonography every six months in patients with cirrhosis is a consideration. Routine health screening measures for other malignancies should be applied diligently.

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