EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) th...

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Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis

Molecular chaperones, including the heat-shock proteins (Hsps), are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins. Hsps have received the most attention in model organisms undergoing experimental stress in the laboratory, and the function of Hsps at the molecular and cellular level is becoming well understood in this context. A complementary focus is now emerging on the Hsps of both model and nonmodel organisms undergoing stress in nature, on the roles of Hsps in the stress physiology of whole multicellular eukaryotes and the tissues and organs they comprise, and on the ecological and evolutionary correlates of variation in Hsps and the genes that encode them. This focus discloses that (a) expression of Hsps can occur in nature, (b) all species have hsp genes but they vary in the patterns of their expression, (c) Hsp expression can be correlated with resistance to stress, and (d) species' thresholds for Hsp expression are correlated with levels of stress that they naturally undergo. These conclusions are now well established and may require little additional confirmation; many significant questions remain unanswered concerning both the mechanisms of Hsp-mediated stress tolerance at the organismal level and the evolutionary mechanisms that have diversified the hsp genes.

/pdf/heat-shock-proteins-molecular-chaperones-and-the-stress-p3ghklf1z7.pdf

Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology

Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-alpha-2b (PegIFN-alpha-2b) or -alpha-2a (PegIFN-alpha-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 (IFN-lambda-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06 x 10(-25)) and African-Americans (P = 2.06 x 10(-3)). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.

Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.

https://www.gastrojournal.org/article/S0016-5085(00)70261-7/pdf

Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B

https://www.journal-of-hepatology.eu/article/S0168-8278(00)80135-X/pdf

Hepatitis B genotypes and the response to interferon therapy.

https://www.gastrojournal.org/article/0016-5085(85)90324-5/pdf

Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications.

To assess the contribution of hepatitis C virus (HCV) in liver disease in Taiwan, antibody to HCV (anti-HCV) was studied by radioimmunoassay in 392 patients with chronic liver disease and in 440 healthy adults and 444 subjects at risk. The anti-HCV prevalence was 0.95% in 420 volunteer blood donors, 90% in 100 hemophiliacs, and 81% in 58 parenteral drug abusers. Anti-HCV was present in 6 (7.7%) of 78 hepatitis B surface antigen (HBsAg)-positive and 28 (65%) of 43 HBsAg-negative patients with chronic hepatitis, 3 (10%) of 31 HBsAg-positive and 13 (43%) of 30 HBsAg-negative cirrhotics, and 7 (17%) of 42 HBsAg-positive and 15 (63%) of 24 HBsAg-negative patients with hepatocellular carcinoma (HCC). An outbreak of non-A, non-B hepatitis revealed 18% of 57 patients to be positive for anti-HCV, and in 29 patients with posttransfusion hepatitis prospectively followed, 7 (24%) developed anti-HCV. Thus, HCV infection appears to play a relatively minor role in HBsAg-positive liver disease in Taiwan but is strongly associated with HBsAg-negative chronic liver disease and HCC. The infection is extremely common in hemophiliacs and parenteral drug abusers.

Hepatitis C Virus Infection in an Area Hyperendemic for Hepatitis B and Chronic Liver Disease: The Taiwan Experience

https://www.gastrojournal.org/article/S0016-5085(96)00486-6/pdf

Ming-Yang Lai

Papers

Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B

Hepatitis B genotypes and the response to interferon therapy.

Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications.

Hepatitis C Virus Infection in an Area Hyperendemic for Hepatitis B and Chronic Liver Disease: The Taiwan Experience

Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C