Hugo Tanno

Hepatitis A virus in stool during clinical relapse

Among 256 patients with acute hepatitis A, 17 (6.6%) had a relapse of the disease between 30 and 90 days after the primary episode. We studied 7 of these patients. Serologic testing showed mean alanine aminotransferase levels of 1668 IU/L during the acute stage, 107 IU/L during the early convalescence, and 1027 IU/L during the relapse. Tests for IgM antibody against hepatitis A virus were positive in the 7 patients at the onset of disease, with decreasing levels in 3 of the 4 patients tested during the evolution of the illness. Stools collected during the relapse phase showed hepatitis A virus by immune electron microscopy, radioimmunoassay, and molecular hybridization using a 32P-labeled cDNA-hepatitis A virus probe. Stools collected from 4 of these patients 6 to 12 months after the onset of disease were negative for the virus. The finding of hepatitis A virus in the stool of these patients during the relapse phase strongly implicates hepatitis A virus as the causative agent of the clinical relapse.

Recombinant interferon alfa-2b following prednisone withdrawal in the treatment of chronic type B hepatitis

The aim of the study was to evaluate the safety and effectiveness of interferon alfa-2b, alone and following prednisone withdrawal, in patients with chronic type B hepatitis. Thirty-five patients (27 men and eight women) were randomly allocated to two treatment groups. Group I (n = 17) received 6 weeks of prednisone followed by interferon alfa-2b (INTRON A, Schering-Plough Corporation) 10 million units subcutaneously, three times a week for 16 weeks. Group II (n = 18) was used as an untreated control group for 24 weeks, after which they received 16 weeks of treatment with the same dose of interferon as Group I. Both groups were followed up for 24 weeks after treatment. In Group I, 10/17 patients (58.8%) eliminated hepatitis B e antigen; 8/17 (47.1%) developed antibodies to hepatitis B e antigen; 9/17 (52.9%) became hepatitis B virus DNA negative and 1/17 (5.9%) was hepatitis B surface antigen negative at the end of follow up. In Group II, during the control phase, 1/18 (5.5%) became hepatitis B e antigen negative. When treated with interferon, 7/15 (46.7%) eliminated the e antigen, and 6/15 (40%) developed antibodies to hepatitis B e antigen and were hepatitis B virus DNA negative at the end of follow up. Serum alanine aminotransferase reached normal levels in all seroconverted patients. Liver biopsies showed a marked reduction of inflammation and disappearance of hepatitis B core antigen in liver cell nuclei in almost all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between Helicobacter pylori infection and cirrhosis in patients with chronic hepatitis C virus.

We evaluated, employing a logistic regression model, the association between Helicobacter pylori infection and cirrhosis in a cohort of 106 patients (57 males; mean age, 52.9 years; range, 20–78 years) with chronic hepatitis C virus (HCV) from Rosario, Argentina. HCV was confirmed by ELISA and PCR. H. pylori status was determined by ELISA. Of the 106 patients evaluated, 47 (44.3%) had cirrhosis. A total of 70.2% (33/47) of cirrhotic patients and 47.5% (28/59) of noncirrhotic patients were H. pylori-positive. In univariate analyses, cirrhosis was associated with age (P = 0.016) and H. pylori-positive status (P = 0.019) but not with gender (P = 0.28) or length of infection (P = 0.35). In multivariate analysis, H. pylori infection (P = 0.037; OR = 2.42; 95% CI = 1.06–5.53) and age (P = 0.033; OR = 1.04; 95% CI = 1.00–1.07) of patients remained significant and independently associated with cirrhosis. In conclusion, our results demonstrate an association between H. pylori infection and cirrhosis in patients with hepatitis C virus.

Unsuccessful therapy with adefovir and entecavir-tenofovir in a patient with chronic hepatitis B infection with previous resistance to lamivudine: a fourteen-year evolution of hepatitis B virus mutations

BackgroundComplex mutants can be selected under sequential selective pressure by HBV therapy. To determine hepatitis B virus genomic evolution during antiviral therapy we characterized the HBV quasi-species in a patient who did no respond to therapy following lamivudine breakthrough for a period of 14 years.Case PresentationThe polymerase and precore/core genes were amplified and sequenced at determined intervals in a period of 14 years. HBV viral load and HBeAg/Anti-HBe serological profiles as well as amino transferase levels were also measured. A mixture of lamivudine-resistant genotype A2 HBV strains harboring the rtM204V mutation coexisted in the patient following viral breakthrough to lamivudine. The L180M+M204V dominant mutant displayed strong lamivudine-resistance. As therapy was changed to adefovir, then to entecavir, and finally to entecavir-tenofovir the viral load showed fluctuations but lamivudine-resistant strains continued to be selected, with minor contributions to the HBV quasi-species composition of additional resistance-associated mutations. At the end of the 14-year follow up period, high viral loads were predominant, with viral strains harboring the lamivudine-resistance signature rtL180M+M204V. The precore/core frame A1762T and G1764A double mutation was detected before treatment and remaining in this condition during the entire follow-up. Specific entecavir and tenofovir primary resistance-associated mutations were not detected at any time. Plasma concentrations of tenofovir indicated adequate metabolism of the drug.ConclusionsWe report the selection of HBV mutants carrying well-defined primary resistance mutations that escaped lamivudine in a fourteen-year follow-up period. With the exception of tenofovir resistance mutations, subsequent unselected primary resistance mutations were detected as minor populations into the HBV quasispecies composition during adefovir or entecavir monotherapies. Although tenofovir is considered an appropriate therapeutic alternative for the treatment of entecavir-unresponsive patients, its use was not effective in the case reported here.

The Spectrum of Nimesulide-Induced-Hepatotoxicity. An Overview

Nimesulide is the unique molecule of the sulphonanilides class of non-steroidal antiinflammatory drugs [NSAIDs]: Nimesulide has analgesic, anti-pyretic, potent anti-inflammatory activities and very good gastro-intestinal [GI] tolerability. Therapeutic action is multifactorial, including cyclooxigenase-2 (COX-2) inhibition, scavenging of free radicals and inhibition of various pathways of inflammation. Nimesulide is oxidatively metabolised via liver cytochromes P450. Several unproven hepatotoxicy-predisposing-factors thought to be present in rheumatologic patients have been linked to a higher incidence of hepatic reactions in this sub-population. However, the molecular mechanism underlying hepatotoxicy remains to be elucidated. Nimesulide has been associated over two decades with reports of severe liver damage. The clinical presentation of nimesulide-related-hepatoxicity includes, malaise, pruritus, a wide range of ALT/AST elevation, and an average 4 fold elevation of alkaline phosphatase and GGT. Liver biopsy shows a predominance of hepatocellular involvement, less frequently cholestatic and mixed patterns. Both, the hepatitis pattern and the mixed-type combining cholestatic jaundice, might evolve into fulminant hepatic failure. However, the incidence of nimesulide-inducedhepatotoxicity is not homogeneous across the medical literature. Indeed, most of the countries find it to be comparable to that of other NSAIDs, while a significant higher hepatotoxicity is suggested by reports from Finland, Ireland and Argentina. Our series in Argentina comprising 43 cases is worrisome particularly because it evidences a significant proportion of severe forms. In the present work we analyze the epidemilogical characteristics of nimesulide-induced-hepatotoxicity and we describe the clinical and histologic spectrum of nimesulide-associated-liver damage based on the comparison of our series of 43 cases and worldwide published observations in the pertinent medical literature.

Octreotide Enhances Portal Pressure Reduction Induced by Propranolol in Cirrhosis: A Randomized, Controlled Trial

BACKGROUND:In vitro, octreotide potentiates vasoconstriction in isolated, preconstricted, mesenteric arterial vessels. In cirrhotic patients, portal pressure (HVPG) reduction induced by propranolol is partly due to splanchnic vasoconstriction.AIM:To evaluate HVPG effects of octreotide administration in cirrhotic patients receiving long-term propranolol.PATIENTS AND METHODS:A randomized, controlled trial. First study: a total of 28 patients were studied at baseline and 30 and 60 minutes after octreotide (200 μg) (N = 14) or placebo (N = 14) and then treated with propranolol for approximately 30 days (106 ± 5 mg/day). Second study: after baseline evaluation patients received octreotide or placebo as they were assigned to in the first study and measurements repeated 30 and 60 minutes later.RESULTS:In the first study baseline HVPG was 18.7 ± 0.9 mmHg and decreased to 17.1 ± 1.1 mmHg and 17.1 ± 1.0 mmHg (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Eight patients decreased their HVPG after octreotide. In the second study baseline HVPG was 15.6 ± 1.3 mmHg (P < 0.01 vs baseline HVPG in first study) and decreased to 14.1 ± 1.2 mmHg and 14.1 ± 1.3 mmHg (25.7 ± 5% lower than baseline HVPG in the first study, P < 0.01) (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Nine patients (2 responders/7 nonresponders to propranolol) decreased their HVPG after octreotide. Octreotide effects may be mediated by potentiation and additive mechanisms.CONCLUSIONS:Octreotide enhances HVPG reduction induced by propranolol in cirrhotic patients.