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.

Based on observations of a limited number of patients, delta (δ) infection has been reported to be infrequent in Taiwan. To further evaluate the role of δ-infection in patients with hepatitis B virus (HBV) infection, serum samples of 493 subjects with acute and chronic HBV infections collected in 1976–85 were studied for anti-δ by radioimmunoassay. Intrahepatic δ-antigen was also studied by immunofluorescence in 12 anti-δ-positive patients. The overall prevalence of δ-infection was 4.7%, consistent with previous studies. δ-Infection had an even yearly distribution in the last decade. However, there were four groups with significantly higher frequencies: (i) 24% of 41 anti-HBe-positive patients with chronic active hepatitis (CAH); (ii) 21% of 14 HBsAg carriers with prominent lobular hepatitis; (iii) two of three HBsAg carriers with intravenous drug abuse; and (iv) two of seven with fulminant hepatitis. On the other hand, δ-infection was uncommon in patients with chronic persistent hepatitis, cirrhosis, hepatocellular carcinoma, classical type B hepatitis, submassive necrosis and asymptomatic HBsAg carriers. δ-Antigen was found in only two patients with CAH; one progressed to cirrhosis, and the other had disease regression on follow-up. Overall, at least half of the δ-superinfected HBsAg-positive patients had a non-progressive course on follow-up.



It was concluded that δ-agent was introduced to Taiwan before 1976. Although it has played a role in some clinical settings of HBV infections, it is generally infrequent in Taiwan. The δ-superinfection apparent in half the patients studied seems to have a non-progressive course.

Delta-agent infection in Taiwan

The evolution of precore stop codon mutation (A1896) and dinucleotide mutation (T1762/A1764) in the basic core promoter (BCP) of hepatitis B virus (HBV) genome during transient seroconversion and seroreversion of hepatitis B e antigen (HBeAg) remains unclarified. Five HBeAg-positive HBV carriers who experienced transient seroconversion followed by seroreversion of HBeAg (Group I, 3.3%) and 3 HBeAg-negative HBV carriers with documented reversion of HBeAg (Group II, 2.5%) in a prospective cohort of 272 patients with chronic hepatitis B were thus identified. The sequential changes at the precore nucleotide 1896 and BCP dinucleotide 1762/1764 were determined by polymerase chain reaction and direct sequencing. At enrollement, precore A1896 and BCP T1762/A1764 were noted in 4 (50%) and 1 (13%) of the eight patients. During a median follow-up period of 58 months (range: 31-76 months), 12 episodes of transient HBeAg seroconversion followed by seroreversion were encountered in Group I patients and 3 episodes of HBeAg seroreversion in Group II patients. Accompanying acute exacerbations were found in two-thirds of patients with either HBeAg seroconversion or seroreversion. Overall, precore nucleotide A1896 remained identical in 73% and 83% of the seroconversion and seroreversion events, respectively. BCP dinucleotide T1762/A1764 remained unchanged in 94% and 92% of the seroconversion and seroreversion events, respectively. At the end of follow-up, only one had both precore and BCP mutations. In conclusion, these data suggested that HBeAg seroreversion might be due to the lack of sustained precore and BCP mutations after HBeAg seroconversion. Although uncommon, HBeAg seroreversion can be associated with hepatitis exacerbation.

Evolution of precore/core promoter mutations in hepatitis B carriers with hepatitis B e antigen seroreversion

Liver transplantation for patients with hepatitis B: prevention of hepatitis B recurrence by intravenous antihepatitis B immunoglobulin and lamivudine.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20331

Origin of serum hepatitis B virus in acute exacerbation: comparison with HBV in the liver and from other exacerbation.

Objectives: Early hepatitis C viral (HCV) kinetics following pegylated interferon-α (PEG-IFN) and ribavirin help to assess treatment in the Western world. Whether this functions in

Ming-Yang Lai

Papers

Delta-agent infection in Taiwan

Evolution of precore/core promoter mutations in hepatitis B carriers with hepatitis B e antigen seroreversion

Liver transplantation for patients with hepatitis B: prevention of hepatitis B recurrence by intravenous antihepatitis B immunoglobulin and lamivudine.

Origin of serum hepatitis B virus in acute exacerbation: comparison with HBV in the liver and from other exacerbation.

Early viral kinetics during treatment of chronic hepatitis C virus infection with pegylated interferon alpha plus ribavirin in Taiwan.