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.

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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.

Of 368 hepatitis B virus (HBV)-infected intravenous drug users, 144 (39%) were positive for antibody to hepatitis D virus (anti-HDV). Anti-HDV-positive HBV carriers had a lower rate of positivity for HBV DNA than did anti-HDV-negative carriers (52 versus 73%, respectively). From 1986 to 1997, the average rate of decrease in the prevalence of HDV infection in this population was 4.7%/year.

Hepatitis D Virus Genotypes in Intravenous Drug Users in Taiwan: Decreasing Prevalence and Lack of Correlation with Hepatitis B Virus Genotypes

Concomitant infection with TT virus and hepatitis B virus (HBV) or hepatitis C virus (HCV) is common. However, the effect of TTV infection on chronic hepatitis B or C is unknown. The prevalence of TTV infection, the effect of TTV infection on the clinical, histological and virological features of patients with chronic hepatitis B or C, and the influence of TTV infection on the HCV response to interferon alfa therapy were studied. A total of 100 asymptomatic hepatitis B surface antigen carriers, 220 patients with HBV-related chronic liver diseases, and 110 patients with chronic hepatitis C treated with interferon alfa (3 million units subcutaneously three times a week for 24 weeks) were enrolled. Serum HCV RNA and serum TTV DNA were detected by the polymerase chain reaction (PCR). Serum HBV DNA and serum HCV RNA level were quantified by branched DNA assays. Infection with TTV was detected in 21.5% of HBV carriers and 37% of HCV carriers. TTV infection had little effect on the clinicopathological course of chronic HBV infection. In chronic hepatitis C, clinical features, histological severity, serum HCV RNA levels, and the response to interferon alfa therapy did not differ between those with and without TTV infection. The loss of serum TTV DNA did not correlate with the biochemical response as did in the loss of serum HCV RNA. In conclusion, TTV infection is found frequently in patients with chronic hepatitis B or C in Taiwan; however, coinfection with TTV does not affect the clinicopathological course of chronic hepatitis B or C and the response to interferon alfa therapy.

TT virus infection in patients with chronic hepatitis B or C: influence on clinical, histological and virological features

Subtypes of hepatitis B virus (HBV) have specific geographic distributions and can serve as epidemiological markers. The relationship of HBV serotypes and genotypes in Taiwan and their correlation wit

Molecular epidemiology of hepatitis B viral serotypes and genotypes in taiwan.

Background: Reactivation of hepatitis B after organ transplantation in hepatitis B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our experience of lamivudine treatment in HBsAg carriers who had post-transplant reactivation of hepatitis B.



Methods: The patients were 15 men and one woman. Nine received kidney transplants, six received heart transplants, and one received a lung transplant. They developed a reactivation of hepatitis B 1–101 months (median, 14 months) after transplantation. They received lamivudine 100 mg daily on a compassionate-use basis, and had regular follow ups. The median pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine aminotransferase level was 357 U/L. Four of the 16 patients were positive for HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%) patients. Three were coinfected with hepatitis C virus.



Results: The overall survival rate was 75%. All four fatal cases had a pretreatment total serum bilirubin level of ≥ 3 mg/dL. Serum HBV-DNA soon became undetectable in 12 survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a lamivudine-resistant strain with variation in the YMDD motif of the HBV polymerase gene developed in three (25%). None had significant adverse reactions to lamivudine treatment.



Conclusions: These results indicated that lamivudine is effective in the treatment of post-transplant hepatitis B reactivation, including patients with dual chronic hepatitis B and C. Early recognition of HBV reactivation and prompt lamivudine treatment are important to prevent mortality.

Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: A 4‐year experience

Plasma samples from 89 asymptomatic hepatitis B surface antigen (HBsAg) positive volunteer blood donors were titrated for HBsAg by radioimmunoassay using the parallel line method. HBsAg titers ranged widely from 0.01 to 325 micrograms/ml. The titers correlated well with hepatitis B viral DNA (HBV DNA) and hepatitis B e antigen (HBeAg) in the serum. The HBsAg titers in 55 HBV DNA positive carriers were 90.7 +/- 61.7 micrograms/ml (Mean +/- SD) vs. 6.3 +/- 12.2 micrograms/ml in the 34 carriers without HBV DNA in the serum. The titers were 93.9 +/- 59.1 micrograms/ml in 56 carriers with HBeAg, 6.4 +/- 10.1 micrograms/ml in 24 anti-HBe-positive carriers, and 4.9 +/- 4.6 micrograms/ml in 9 HBeAg/anti-HBe-negative carriers. 50 (89.3%) of the 56 HBeAg-positive carriers had HBV DNA, in contrast to four (16.7%) of 24 anti-HBe-positive carriers. The study indicated that high-titered HBsAg carriers were much more likely to be infectious, and confirmed that HBeAg is a practical marker of infectivity. Absence of HBeAg, however, did not exclude infectivity in asymptomatic HBsAg carriers, inasmuch as one-sixth of the carriers had HBV DNA.

Ming-Yang Lai

Papers

Hepatitis D Virus Genotypes in Intravenous Drug Users in Taiwan: Decreasing Prevalence and Lack of Correlation with Hepatitis B Virus Genotypes

TT virus infection in patients with chronic hepatitis B or C: influence on clinical, histological and virological features

Molecular epidemiology of hepatitis B viral serotypes and genotypes in taiwan.

Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: A 4‐year experience

Serum HBsAg, HBeAg, anti‐HBe, and hepatitis B viral DNA in asymptomatic carriers in Taiwan