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Biomedical subjects

J P Benhamou

Publications and source records attributed to J P Benhamou.

At least 19 recordsLinked to original sources
PubMed1995

Hepatitis C virus genotypes in French blood donors.

The prevalence of different hepatitis C virus (HCV) genotypes in HCV infected individuals and the relation between the HCV genotypes and the source of the infection are controversial. The aim of this study was to determine the HCV genotypes in French blood donors. Fifty-one anti-HCV positive blood donors were studied with detectable serum HCV RNA by nested polymerase chain reaction (PCR) using primers derived from the 5' non-coding region. For genotyping HCV, we used a method based on analysis of the restriction fragment length polymorphisms (RFLP) after amplification by PCR of the HCV non-structural 5 (NS5) genome domain. Using this technique, the genotypes of 39 of the 51 blood donors (76%) were determined. Three previously described genotypes were found: 19 blood donors were infected by HCV genotype I (37%), 14 were infected by HCV genotype II (27%), 3 were infected by HCV genotype III (6%), and 3 were coinfected by two genotypes (6%). All three blood donors infected with two different genotypes were intravenous drug abusers. A past history of intravenous drug abuse was more frequent in blood donors with HCV genotype I. However, there was no difference in alanine transaminase (ALT) levels, histological lesions, and RIBA-2 patterns in blood donors infected with either HCV genotype I or HCV genotype II. These findings indicate that most HCV genotypes isolated from French blood donors belong to HCV genotype I and HCV genotype II, and that risk factors for HCV infection may differ for different genotypes of HCV.

Adult↗
PubMed1995

Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C.

BACKGROUND & AIMS: In patients with chronic hepatitis C treated with interferon alfa, sustained normalization of alanine aminotransferase was observed in about 20%, and no predictive factor of response could be clearly identified. The aims of this study were to assess the efficacy of an escalating dose of interferon and to determine the predictive factors of response. METHODS: Seventy-five patients were randomly assigned to two groups. Twenty-five patients received a dosage of 3 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, and 50 patients received a dose that was increased to 5 million units at 8 weeks in nonresponders and to 10 million units 8 weeks later in persistent nonresponders. Multivariate analysis was performed to determine the features associated with response. RESULTS: A sustained response was observed in 17% of the patients with constant dosage and in 19% of patients with an escalating dosage. Low pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype were found to be independent predictive factors of sustained response. CONCLUSIONS: In patients with chronic hepatitis C, an escalating dosage of interferon did not improve the overall rate of response. Low pretreatment serum hepatitis C virus RNA levels and genotype other than 1b were the only predictive factors of sustained response.

Adolescent↗
PubMed1995

Ischemic hepatitis due to obstructive sleep apnea.

The case of an obese patient who developed massive centrilobular liver cell necrosis, severe coagulopathy, acute renal failure, and encephalopathy is presented. Hypovolemia and heart failure were absent, but the acute liver disease was associated with severe arterial hypoxemia due to obstructive sleep apnea that was shown by the nocturnal blood oxygen desaturation, the results of the polysomnographic study, and normal baseline pulmonary function tests. In this obese patient, liver cell necrosis was caused by severe liver cell hypoxia secondary to severe arterial hypoxemia as a consequence of obstructive sleep apnea associated with a Pickwickian syndrome. This observation is consistent with the hypothesis that liver ischemia was directly related to severe arterial hypoxemia.

Female↗
PubMed1995

Hepatitis B virus precore mutations and HBeAg negative reactivation of chronic hepatitis B after interferon therapy.

The objective of this study was to look for HBV precore mutations in three patients with chronic active hepatitis B who developed HBV-DNA-positive/HBeAg-negative reactivation after HBe seroconversion induced by interferon therapy. Direct sequencing of polymerase chain reaction products was performed on serum collected before and after HBe seroconversion. In two patients precore sequence showed only wild-type HBV before and after interferon therapy. In one patient, precore sequence showed only wild-type HBV before interferon therapy and a mixed infection by wild-type HBV and precore mutant viruses (1858 and 1896 nucleotide mutations) after treatment. The presence of HBeAg/anti-HBe immune complexes was found after HBe seroconversion in all cases. Our results suggest that: 1) precore mutations are not always found in patients with chronic hepatitis B who develop HBV DNA-positive/HBeAg-negative reactivation; and 2) HBeAg negativity, despite the presence of wild-type HBV, might be due to HBeAg/anti-HBe immune complexes. We speculate that the production of these immune complexes may be favored by interferon therapy.

Adult↗
PubMed1994

Expression of complement-regulatory proteins in normal and UW-preserved human liver.

BACKGROUND/AIMS: Somatic cells are protected against complement-mediated injury by specialized membrane proteins, known as complement-regulatory proteins (CRP). The knowledge of the pattern of CRP expression in the liver is important to evaluate the role of complement-mediated injury in graft rejection. METHODS: We determined the distribution of four main CRP: membrane cofactor protein (MCP), decay accelerating factor (DAF), protectin, and complement receptor 1 (CR1) in 30 histologically normal livers, 13 samples from University of Wisconsin cold-storage solution (UW)-preserved tissue and 17 postoperative biopsies of UW-preserved allografts. RESULTS: In normal liver, hepatocytes expressed only MCP. Bile duct cells were reactive for MCP and protectin. Sinusoidal endothelial cells expressed MCP and protectin but displayed no or faint expression of DAF. Endothelial cells of portal vessels and centrilobular veins expressed high levels of DAF, MCP, and protectin. No expression of CR1 was observed. No change in CRP expression was usually detected after UW preservation, except for protectin, induced on hepatocytes in 9 samples of UW-preserved liver tissue and in 9 allografts. CONCLUSIONS: Hepatocytes and sinusoidal endothelial cells, which have a defective expression of CRP, might be at risk for complement-mediated injury. However, this risk is not aggravated after UW preservation.

Adenosine↗
PubMed1994

Expression of cytokine-dependent adhesion molecules in postreperfusion biopsy specimens of liver allografts.

BACKGROUND/AIMS: Allogeneic recognition of donor cells by host T lymphocytes requires the expression of cytokine-dependent molecules, such as class II major histocompatibility antigens, intracellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). In the liver, activation of Kupffer cells after ischemic injury during the transplantation procedure may result in an early induction of cytokine-dependent molecules. METHODS: The pattern of induction of ICAM-1, HLA-DR, HLA-DQ, and LFA-3 was investigated in 30 postreperfusion surgical biopsy specimens of liver allografts by an immunohistochemical technique. RESULTS: Two patterns of induction were observed: focal or diffuse. On hepatocytes, ICAM-1 was induced in 22 cases (11 focal, 11 diffuse), HLA-DR in 18 cases (13 focal, 5 diffuse), HLA-DQ in 13 cases (3 focal, 10 diffuse), and LFA-3 in 1 case (focal). On bile duct cells, HLA-DR was expressed in 19 cases, associated with HLA-DQ in 7 cases. No induction of ICAM-1 and LFA-3 was detected. Compared with the other patients, the group of patients with diffuse postoperative hepatocellular induction of ICAM-1 was characterized by higher preharvesting serum transaminase levels in the donor (P < or = 0.001), suggestive of preoperative ischemic injury, and increased incidence of acute graft rejection (P = 0.04). CONCLUSIONS: Preoperative warm ischemia may modify the immunogenicity of liver allografts.

Adult↗
PubMed1994

Expression of cytokine-dependent immune adhesion molecules by hepatocytes and bile duct cells in chronic hepatitis C.

BACKGROUND/AIMS: The pathogenesis of liver cell injury in chronic hepatitis C is poorly understood. To test whether immune-mediated mechanisms might be involved in the pathogenesis of liver cell injury during infection by hepatitis C virus, the expression of cytokine-dependent immune molecules by hepatocytes and bile duct cells during chronic hepatitis C was studied. METHODS: In 35 patients, expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM) 1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry and scored by a semiquantitative grading system. Statistical analysis was performed using Spearman's test and t test. RESULTS: Class I HLA antigens were induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3 were detected on hepatocytes in piecemeal necrosis and intralobular clusters. Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases. Expression levels of immune molecules on hepatocytes correlated with aminotransferase activity (P < 0.035), histological activity (P < 0.001), and score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM-1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P < 0.015). CONCLUSIONS: These results suggest the involvement of immune-mediated mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.

Adult↗
PubMed1994

Etiology of chronic hepatitis in France: predominant role of hepatitis C virus.

The aim of this study was to assess the causes of histologically proven chronic hepatitis in a series of 357 consecutively admitted patients. Patients with chronic alcohol intake above 50 g per day, Wilson's disease, idiopathic hemochromatosis or homozygous alpha-1 antitrypsin deficiency were excluded. Sera of all patients were tested for antibodies to hepatitis C virus with second-generation enzyme-linked immunoassay and recombinant immunoblot assay, for markers of hepatitis B and hepatitis D viruses, and for autoantibodies. Detection of hepatitis C viral RNA by polymerase chain reaction was attempted if recombinant immunoblot assay was indeterminate, or if both viral and autoimmune markers were absent. If no serum markers, including HCV RNA, were found, the cause of chronic hepatitis was considered as unknown. The cause of chronic hepatitis was found in 343 cases (96.4%), including three patients with HCV RNA as the only marker. Chronic hepatitis was related to hepatitis C virus in 51.8%, to hepatitis B virus in 32.8% (including hepatitis D infection in 3.1%), and to autoimmune hepatitis in 5.9% of cases, respectively. No case of drug-induced chronic hepatitis was observed in this series, and in 5.9% of cases, there were probably multiple causes. Finally, in 3.6% of the cases the cause of chronic hepatitis remained unknown despite extensive evaluation suggesting the existence of a non-A, non-B, non-C viral agent.

Adult↗
PubMed1994

Hepatitis C virus (HCV) viremia in human immunodeficiency virus-seronegative and -seropositive patients with indeterminate HCV recombinant immunoblot assay.

Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The significance of an indeterminate RIBA result, defined by reactivity to only one HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative or -positive subjects with an indeterminate RIBA have HCV viremia detectable by polymerase chain reaction was investigated. An indeterminate RIBA was found in 48 (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive. HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV-negative subjects (50%) with an indeterminate RIBA (P < .05). These results suggest an impaired anti-HCV response associated with HIV infection.

Alanine Transaminase↗
PubMed1993

Chronic non-B, non-C hepatitis among blood donors assessed with HCV third generation tests and polymerase chain reaction.

Forty five blood donors with increased serum aminotransferases levels had liver histologic assessment and were tested for antibodies to hepatitis C virus (anti-HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these 45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no known cause of chronic hepatitis and no risk factor for parenterally acquired viral infection was found in them. This observation supports the hypothesis that a non-B, non-C virus might be implicated in chronic hepatitis. However, this hypothesis remains to be demonstrated.

Blood Donors↗
PubMed1993

Assessment of screening tests for transfusion-associated non-A non-B hepatitis.

Non-A non-B hepatitis is the most common serious sequela of blood transfusion, and its screening has become an essential goal of blood transfusion centers. Before 1989, two surrogate screening tests (for alanine aminotransferase and for antibody to hepatitis B core antigen) were used; in 1989, a direct test for the antibody to hepatitis C virus (the main agent of this hepatitis) was developed. The French National Agency for the Development of Medical Evaluation undertook an investigation to determine the optimal prevention strategy for posttransfusion non-A and non-B hepatitis (PTH). A detailed literature review was performed, complemented by expert group opinion. The performance of each test was derived indirectly by calculating the number of cases of PTH averted by each test. Hepatitis C virus testing is probably the most promising strategy, but different policies can be developed given the uncertainties of scientific data. Cost considerations should be taken into account in identifying the best screening strategy.

Alanine Transaminase↗
PubMed1993

Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing.

To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV positive) French non-drug-addicted homosexual men admitted for chronic viral hepatitis. Anti-HCV were detected with second- and third-generation ELISAs (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3, respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57 ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive results. ELISA2 positive results were more frequent with frozen serum samples than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV positive patients. ELISA3 seems to give more specific results. We conclude that the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French homosexual men with chronic hepatitis (3.8% after exclusion of transfused patients). This low prevalence suggests that homosexual transmission of HCV is relatively uncommon.

Adult↗
PubMed1992

[Definition of asymptomatic biliary lithiasis].

Asymptomatic biliary lithiasis can be defined as biliary lithiasis having determined no complication and no episode of biliary pain. Biliary pain is a consequence of acute increase of pressure inside the biliary tract. The increased pressure is induced by a stone transiently obstructing the cystic duct or the Oddi sphincter. In most patients, the site of the pain is epigastric. The level of the pain is high. The duration of the episode of biliary pain is usually less than 5 hours. Abdominal pain having other characteristics, dyspepsia, and headache are not related to biliary lithiasis.

Cholelithiasis↗
PubMed1992

Pharmacokinetics of lomefloxacin in patients with cirrhosis.

The effect of liver failure on the pharmacokinetics of lomefloxacin was studied in 12 patients with cirrhosis. Patients received a single oral dose of 400 mg lomefloxacin, and blood and urine samples were collected at intervals over the next 48 hours. The concentrations of lomefloxacin in all samples were measured using high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) maximum plasma concentration (Cmax) in these patients was 3.9 +/- 1.20 micrograms/mL. The mean time to maximum serum concentration (Tmax) was 2.1 +/- 2.6 hours, and the mean elimination half-life (t1/2) was 9.16 +/- 1.93 hours. Mean renal clearance was 88.9 +/- 38.0 mL/min/1.73 m2, and the mean nonrenal clearance was 61.6 +/- 19.0 mL/min/1.73 m2, which corresponded to 41% of the total body clearance. No correlations were observed between nonrenal clearance and hepatic insufficiency (Pugh score) or nonrenal clearance and plasma bilirubin. These results show that liver failure does not per se affect lomefloxacin kinetics. Thus, no adjustments in lomefloxacin dosages appear to be necessary for patients with impaired liver function tests.

Adult↗
PubMed1992

A randomized trial of prednisolone in patients with severe alcoholic hepatitis.

BACKGROUND: Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. METHODS: We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. RESULTS: One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. CONCLUSIONS: Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.

Double-Blind Method↗
PubMed1992

Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to anti-HBs seroconversion in patients with chronic hepatitis B.

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.

Adult↗
PubMed1992

Drug-induced prolonged cholestasis in adults: a histological semiquantitative study demonstrating progressive ductopenia.

Drug-induced acute hepatitis may be followed by prolonged cholestasis despite the withdrawal of the drug. Eight patients suffering from prolonged cholestasis caused by several drugs were investigated with sequential liver biopsies. At the early stage, lesions of acute cholangitis were observed in most patients; at the chronic phase, ductopenia, defined by the absence of interlobular bile ducts in at least 50% of small portal tracts, was demonstrated in all patients. Ductopenia might be the consequence of acute cholangitis; the degree of ductopenia and the chronicity of the disease might be directly related to the severity of the early acute damage of bile ducts. Consequently, in patients with severe cholestasis related to drugs, research of early morphological signs of acute cholangitis and then of ductopenia seems to be important.

Adult↗