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...

/pdf/peginterferon-alfa-2a-plus-ribavirin-for-chronic-hepatitis-c-lnfdfx9cd4.pdf

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.

Probable reinfection with hepatitis C virus in a chronic hepatitis C patient with a sustained response to combination therapy.

Background/Aim: Hepatitis B e antigen (HBeAg) seroconversion is an important event in the natural history of chronic hepatitis B virus (HBV) infection. Whether early dynamics of HBeAg index ratio could predict therapeutic endpoint of HBeAg seroconversion in patients receiving lamivudine remains unclear and thus deserves investigation.



Methods: A total of 52 patients (males/females, 40/12; mean age, 31.1±7.5 years) with HBeAg-positive chronic hepatitis B and serum alanine aminotransferase (ALT) level ≥5 × upper limit of normal were enrolled. They received daily 100 mg lamivudine for at least 1 year. Pretreatment HBeAg index ratio and the dynamics during treatment [early serologic response (ESR) and serologic breakthrough (SB)] between responders and non-responders were compared.



Results: Of these 52 patients, mean pretreatment serum ALT level was 580 IU/l and baseline HBeAg index ratio (S/N) was 37.9. The overall 1-year on-treatment combined response rate was 50%. By using linear regression analysis, HBeAg index ratio was positively correlated with serum HBV DNA level (Pearson's correlation coefficient: 0.62, P<0.0001). By using multivariate logistic regression analysis, ESR could predict the success of treatment response (P=0.0302), and SB had a 90% positive predictive value of treatment failure.



Conclusions: HBeAg index ratio is closely correlated with serum HBV DNA level, and the dynamics of HBeAg index ratio may predict 1-year on-treatment combined response to lamivudine in HBeAg-positive chronic hepatitis B patients.

Dynamics of hepatitis B e antigen index ratio correlate with treatment response in chronic hepatitis B patients.

Patients with hepatitis B virus (HBV) infection have a higher morbidity and mortality after heart transplantation (HT). HBV infection is endemic in Taiwan. We studied the effect of lamivudine treatment of HBV infection after HT. From July 1987 to July 2005, 252 patients underwent HT. All recipients and donors underwent routine screening of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e antigen, and an alanine aminotransferase (ALT) level before HT. When ALT was two times greater than the upper limit of normal or serum bilirubin was higher than 3 mg/dL in HBsAg-positive patients, HBV-DNA were checked by a branched DNA assay or polymerase chain reaction. When HVB-DNA was greater than 100,000 copies/mL, lamivudine (100 mg per day) was prescribed indefinitely. There were 14 patients under lamivudine treatment after HT, among whom, none suffered severe adverse reactions from lamivudine. Four patients died: one due to end-stage cirrhosis while awaiting liver transplantation at 14 months after HT. Two died of sudden death at 54 months and 138 months after HT. Another died of diffuse B cell lymphoma at 62 months after HT. All the survivors have normal ALT and undetectable HBV-DNA after lamivudine treatment. But the YMDD mutant was detected in two patients. With successful treatment of HBV infection in HT, it is not necessary to exclude HBV infection patients from HT.

Successful Treatment of Hepatitis B Virus Infection With Lamivudine After Heart Transplantation

Hepatitis C virus (HCV) carriers usually have antibodies to HCV ; however, there are viremic individuals without these antibodies. To investigate whether variations of the viral genome are responsible for this discrepancy, the nucleotide and deduced amino acid sequences of HCV capsid and nonstructural regions obtained from 15 viremic patients were examined. These 15 patients were infected with type 1b HCV, and 10 did not have antibody to HCV assayed with second-generation tests. The nucleotide homology of the 5 seropositive and 10 seronegative patients with the HCV prototype sequence were 91.6% and 91.9%, respectively, in the capsid region. There was no apparent difference in the deduced amino acid sequences between the two groups of patients studied (94% vs. 95%). The nucleotide and amino acid sequences of a part of the nonstructural region 3 also showed similar results. These findings suggest that absence of antibodies against both capsid and nonstructural peptides in HCV carriers is not caused by genetic heterogeneity of the viral epitopes.

Ming-Yang Lai

Papers

Probable reinfection with hepatitis C virus in a chronic hepatitis C patient with a sustained response to combination therapy.

Dynamics of hepatitis B e antigen index ratio correlate with treatment response in chronic hepatitis B patients.

Successful Treatment of Hepatitis B Virus Infection With Lamivudine After Heart Transplantation

Absence of extensive genetic heterogeneity of hepatitis C virus in antibody-negative chronic hepatitis C.

Anti-HBs reactivity in hepatitis B surface antigen positive serum samples--with special emphasis on heterotypic antibody.