The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon‐α (IFN‐α). To assess the factors leading to virus eradication by IFN‐α, patients whose first treatment by IFN‐α failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2‐PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN‐α therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment. J. Med. Virol. 68:221–228, 2002. © 2002 Wiley‐Liss, Inc.

PURPOSE:To assess the efficacy, morbidity, and mortality involved in the creation of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with refractory ascites in Child-Pugh classes B and C.MATERIALS AND METHODS:Forty-eight consecutive patients with refractory ascites were treated with TIPS creation in a tertiary care institution. They were followed for a median of 337 days (range, 3-1376 d).RESULTS:TIPS significantly decreased the portohepatic pressure gradient (20.7 +/- 5.9 mm Hg vs. 6.8 +/- 4.1 mm Hg; P < .0001). Seventy-three percent of patients had complete or partial response. One year after TIPS creation, survival was 73% in Child class B patients and 56% in Child class C patients. Thirteen patients experienced procedural complications (portal vein thrombosis, peritoneal bleeding, acute renal failure, pneumothorax, hemoptysis, spontaneous bacterial peritonitis, and heart failure) and TIPS creation was considered the cause of death in five patients (10.4%). Primary patency was 65% at 3 months and 23% at 1 year, but shunt obstruction was accessible for a second intervention. Ten patients (21%) had de novo encephalopathy after TIPS creation.CONCLUSIONS:This series suggests that TIPS is an effective treatment for refractory ascites; however, it is a challenging procedure and serious complications--usually renal and heart failure--can be seen. A careful selection of patients is mandatory.

ABSTRACTHepatitis C virus (HCV) populations persist in vivo as a mixture of heterogeneous viruses called quasispecies. The relationship between the genetic heterogeneity of these variants and their responses to antiviral treatment remains to be elucidated. We have studied 26 virus strains to determine the influence of hypervariable region 1 (HVR-1) of the HCV genome on the effectiveness of alpha interferon (IFN-α) therapy. Following PCR amplification, we cloned and sequenced HVR-1. Pretreatment serum samples from 13 individuals with chronic hepatitis C whose virus was subsequently eradicated by treatment were compared with samples from 13 nonresponders matched according to the major factors known to influence the response, i.e., sex, genotype, and pretreatment serum HCV RNA concentration. The degree of virus variation was assessed by analyzing 20 clones per sample and by calculating nucleotide sequence entropy (complexity) and genetic distances (diversity). Types of mutational changes were also determined by calculating nonsynonymous substitutions per nonsynonymous site (Ka) and synonymous substitutions per synonymous site (Ks). The paired-comparison analysis of the nucleotide sequence entropy and genetic distance showed no statistical differences between responders and nonresponders. By contrast, nonsynonymous substitutions were more frequent than synonymous substitutions (P≤ 0.05) in responders, but there was no significant difference in nonresponders. Nonsynonymous substitutions tended to be more frequent than synonymous substitutions in women (P= 0.06) but not in men. Nucleotide entropy and genetic distances were significantly related to serum RNA concentration (P≤ 0.01). Our findings suggest that after controlling for the major determinants of interferon response, neither complexity nor diversity of the HVR-1 region is associated per se with virus eradication. Because a higher proportion of nonsynonymous substitutions than synonymous substitutions was found only in responders, host anti-HCV-specific immune response rather than viral factors may be playing an important role in the interferon response.

BACKGROUND. Prostate-specific antigen (PSA) is the most important tumor marker in prostate cancer diagnosis and follow-up. Its catabolism by the liver has not influenced its use as a prostate marker until the recent report of a significant increase in a man and a woman with acute hepatitis. In addition FSA was detected-in liver tumor extracts, which warranted its evaluation in liver cytolysis and hepatacellular carcinoma. In this study, PSA was evaluated in a cohort of both sexes presenting either acute hepatitis or hepatacellular carcinoima.METHODS. Forty-two patients with acute hepatitis (21 male patients, 21 female patients) and 54 patients with hepatocellular carcinoma (31 male patients, 23 female patients) were tested for PSA by equimolar immunoassay (Abbott AxSYM Total PSA, Abbott Diagnostics, Rungis, France) and for relevant liver biological parameters (alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin rate).RESULTS. PSA was undetectable in all the female patients and was consistent with age in the males (PSA median and range in acute hepatitis, 0.36 mu g/l (range, 0.05-1.3); in hepatocellular carcinoma, 0.36 mu g/l (range, 0.02-3.9)). It did not correlate with alpha-fetoprotein and aminotransferases.CONCLUSIONS. Our results confirm the well-established reliability of PSA, and show that PSA remains a valid prostate marker in patients with acute hepatitis and hepatocellular carcinoma. (C) 1999 Wiley-Liss Inc.

The optimal management of ruptured gastric varices in patients with cirrhosis has not been codified yet. The present study reports the use of transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory gastric variceal bleeding. Thirty-two consecutive patients were included. All had been unresponsive to vasoactive agents infusion, sclerotherapy, and/or tamponade and were considered poor surgical candidates. They were followed-up until death, transplantation, or at least 1 year (median: 509 days; range 4 to 2,230). Hemostasis was achieved in 18 out of 20 patients actively bleeding at the time of the procedure. In the whole sample of 32 patients, rebleeding rates were 14%, 26%, and 31%, respectively at 1 month, 6 months, and 1 year. De novo encephalopathy was observed in 5 (16%) patients. Seven patients experienced complications and consequently 4 of these patients died. TIPS primary patency rates were 84%, 74%, and 51%, respectively, at 1 month, 6 months, and 1 year. For the same periods of time, survival rates were 75%, 62%, and 59%. These results suggest that TIPS can be used in cirrhotic patients with refractory gastric variceal bleeding and are effective in achieving hemostasis as well as in preventing rebleeding.

Objective beta-blockers have been shown to reduce portal pressure in patients with cirrhosis and limit the development of portosystemic shunts in portal hypertensive animals. Thus, a randomized double-blind trial was conducted to evaluate propranolol in the prevention of the development of large oesophageal varices in patients with cirrhosis without varices or with small varices.Methods One hundred and two patients received long-acting propranolol (160 mg/day) and 104 patients received a placebo. At inclusion, there was no significant difference between the two groups in terms of clinical characteristics or biochemical tests. At 2 years, the size of varices was estimated on video recordings.Results One-third of the patients were lost to follow-up, and 95%/97% of the remaining patients were compliant in the propranolol and placebo groups, respectively. At 2 years, the proportion of patients with large varices was 31% in the propranolol group and 14% in the placebo group (P < 0.05). Three and four patients bled in the propranolol and placebo groups, respectively, and nine and ten died, respectively.Conclusion This trial suggests that propranolol administration cannot be recommended for the prevention of the development of large oesophageal varices in patients with cirrhosis; thus other studies are needed in selected subgroups of patients. Eur J Gastroenterol Hepatol 11:741-745 (C) 1999 Lippincott Williams & Wilkins.

The relationship between serum hepatitis C virus (HCV) RNA and the outcome of alpha-interferon (alpha-IFN) therapy in patients with chronic hepatitis C has important implications for therapeutic research and clinical care. Serum HCV RNA was tested for HCV genotype and quantified by a standardized reverse transcriptase-polymerase chain reaction assay as a measure of viral load in a cohort of 130 patients with chronic hepatitis C treated with alpha-IFN at a standard dose of 3 million units three times a week scheduled for 6 (n = 50) or 12 months (n = 76). Twenty-one of 126 evaluable patients (16.7%) developed a sustained complete response to alpha-IFN according to biochemical and virological criteria. The 3 pretreatment independent factors associated with a sustained complete response were a low baseline serum HCV RNA concentration, non-1 HCV genotype, and female sex. A multivariate logistic regression model, with pretreatment and month 1 variables, showed that a lower baseline serum HCV RNA concentration, female sex, and a greater suppression of RNA were the significant predictors of sustained complete response. The lowest baseline serum HCV RNA concentration was observed in patients with genotype 2 infection and the greatest decrease in HCV RNA from baseline to month 1 in those with genotype 3. The findings suggest that measuring HCV RNA in serum before and soon after begining treatment can be helpful for selecting patients who are most likely to have a sustained complete response to standard schedule of alpha-IFN and for identifying patients in whom alternative strategies should be examined. (C) 1998 Wiley-Liss, Inc.