Lack of evidence for the heterosexual transmission of hepatitis C.
(57/3013)
The importance of sexual transmission in the epidemiology of hepatitis C virus (HCV) infection is still controversial. To assess the risk of heterosexual HCV transmission, we examined eighty patients with chronic HCV-associated liver disease and their spouses in a cross-sectional clinical and serological cohort study. Serum samples from index patients and their spouses were assayed for HCV antibodies and HCV RNA. In the couples positive for both, further HCV genotyping was done. A questionnaire addressing points such as additional risk factors for HCV infection, sexual behaviour or duration of partnership was completed by all couples. HCV antibodies were detected in four (5%) spouses, of whom three (4%) were also positive for HCV-RNA. HCV genotyping revealed concordance (genotype 1) in two couples, indicating a risk of interspousal HCV transmission of 2.5%. Spouses of patients with HCV viraemia and chronic liver disease have a low risk for acquiring HCV. Even long-term spouses seem not to be at increased risk. We therefore suggest that the risk of HCV transmission between monogamous sex partners does not depend on the duration of sexual exposure. (+info)
Hepatitis C virus genotyping in relation to neu-oncoprotein overexpression and the development of hepatocellular carcinoma.
(58/3013)
The distribution of hepatitis C virus (HCV) genotypes among Egyptian patients positive for anti-HCV was determined and their influence, when combined with neu-oncoprotein overexpression, on the development of hepatocellular carcinoma (HCC) was examined. The study groups included asymptomatic carriers (ASC) and patients with chronic active hepatitis (CAH) and HCC. HCV genomes were detected in the sera of 27 ASC, 29 CAH and 33 HCC patients known to have HCV infection defined by EIA and recombinant immunoblotting techniques (Inno-LiA) as well as by reverse transcriptase (RT)-PCR. The HCV genotype was determined by a reverse hybridisation technique (Inno-LiPA I and II), whereas neu-overexpression was detected by the Oncogene Science EIA Kit. Eighty-nine patients were eligible for HCV genotyping; 75 patients (84.3%) were infected with a single genotype, including 1a in 11 patients (12.4%), 1b in 2 patients (2.2%) and 2a in 10 patients (11.2%). Genotype 4 (a or c+d) was detected in 51 patients (57.3%) and only one patient had genotype 10a (1.2%). Fourteen patients (15.7%) showed mixed infection; eight of them had 1a+4 (a or c+d) and four had 2a+4 (a or c+d); the remaining two cases had 1a+2a and 1b+2a. The results revealed an increased incidence of genotype 4 in CAH and HCC patients in comparison with ASC. There was also a significant overexpression of neu-oncoprotein in CAH and HCC patients compared with ASC, which was significantly associated with subtype 4 infection. The results suggest that infection with subtype 1a and 4 HCV may be considered a risk factor for the induction of neu-overexpression and subsequent development of HCC. (+info)
Interferon treatment of chronic hepatitis C in patients cured of pediatric malignancies.
(59/3013)
BACKGROUND AND OBJECTIVE: Chronic hepatitis C was a frequent complication in patients treated for malignancy until the introduction of anti-HCV screening tests for blood donors. The association between chronic hepatitis C and progression to cirrhosis and hepatocellular carcinoma has been reported in about 20% and 5% of patients, respectively, within 20-30 years of infection. In adult patients, interferon has proved to be effective in decreasing the abnormal values of transaminases and the level of HCV viremia. Our purpose was to assess efficacy of and tolerance to interferon in a group of young patients who had acquired HCV infection during a period of chemotherapy. DESIGN AND METHODS: Interferon-a (IFN) was administered to 26 adolescents and young adults (13 males, age range 17-36 years; median age 24) with chronic hepatitis C, including 4 with hepatitis B virus co-infection, who had been treated for leukemia or solid tumor 5 to 19 years before joining this trial. Patients were treated with natural IFN alpha at a dose of 4 MU/m(2) thrice weekly for 12 months and followed up for another 6 months thereafter. RESULTS: Nine patients stopped treatment during the first 6 months because of side effects (2 cases) or lack of response. At the end of the trial, 8 (31%) cases had responded, with alanine amino-transferase normalization and clearance of hepatitis C virus (HCV) RNA. A sustained response was only documented in 15% of cases, however, irrespective of any hepatitis B virus co-infection. The 2 patients with HCV genotype 2 were both responders, whereas only 8% of those with genotype 1 responded. INTERPRETATION AND CONCLUSIONS: These data show that the efficacy of IFN in this series of young patients is similar to that reported for otherwise healthy adults with hepatitis C. Patients with genotype 2 are strong candidates for IFN treatment while other therapeutic strategies should be designed for patients with HCV genotype 1. (+info)
Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin.
(60/3013)
Increased levels of hepatic iron may impair the response of patients with chronic hepatitis C to treatment with interferon-alfa, but combination therapy with ribavirin has demonstrated efficacy in the treatment of hepatitis C. When used alone or with interferon-alfa, ribavirin may cause a dose-dependent reversible hemolytic anemia. We compared the extent and cellular localization of iron deposition in liver tissue from biopsy specimens obtained before and after 36 weeks of therapy with ribavirin or placebo for 59 patients with chronic hepatitis C. Paired slides were available for review from 26 ribavirin and 27 placebo recipients. Iron deposition was assessed using coded slides stained with Perls Prussian blue and was semi-quantitated in hepatocytes, Kupffer cells, and areas of fibrosis. The overall iron score fell by 0.96 in the placebo group and increased 1.69 in the ribavirin recipients. Iron was deposited mainly in hepatocytes; the hepatocyte iron score increased from 2.19 to 3.81 in the ribavirin group. The amount of iron staining in Kupffer cells declined in the placebo group and increased slightly in the ribavirin group. Iron changes in areas of fibrosis were minor and did not differ between groups. Increased total hepatic iron deposition occurred during a 9-month course of ribavirin. Ribavirin-associated hemolysis deposits iron preferentially in hepatocytes. This increased deposition of hepatic iron does not seem to affect the biochemical or histologic response to ribavirin therapy but may have implications for hepatocyte susceptibility to future injury. (+info)
Liver infiltrating T lymphocytes express interferon gamma and inducible nitric oxide synthase in chronic hepatitis C virus infection.
(61/3013)
BACKGROUND: Pathogenesis of hepatitis C virus (HCV) associated liver injury is thought to be due to the host antiviral immune response. Using a quantitative, competitive RT-PCR technique, we recently showed that expression of interferon gamma (IFN-gamma) and IFN-gamma inducible type of nitric oxide synthase (iNOS) is increased in homogenised liver tissue of patients with chronic HCV infection. AIMS: To determine the cellular origin of IFN-gamma and iNOS expression and to examine the hypothesis that T cell derived IFN-gamma secretion induces iNOS in hepatocytes in chronic HCV infection. METHODS: By applying a non-radioactive in situ hybridisation method combined with indirect immunofluorescence, 33 liver biopsy specimens from patients with chronic HCV infection were studied for cellular expression of IFN-gamma and iNOS mRNA. RESULTS: In chronic HCV infection, both IFN-gamma and iNOS gene expression were significantly increased. IFN-gamma and iNOS mRNA were observed in CD3+ lymphocytes infiltrating portal tracts and hepatic lobules, but not in hepatocytes. CONCLUSIONS: Results are consistent with previous reports that IFN-gamma and iNOS transcripts are elevated in chronic HCV infection. In contrast to the hypothesis, IFN-gamma expressing T cells do not induce iNOS in hepatocytes, but probably in T cells. T lymphocytes expressing IFN-gamma and/or iNOS have the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic hepatitis C. (+info)
Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection.
(62/3013)
BACKGROUND: Upregulation of Th1 associated intrahepatic cytokines in chronic hepatitis C virus (HCV) infection should lead to a significant non-specific cellular immune response, a prerequisite for viral clearance. However, to date, the role of this non-specific response in HCV has been understudied. AIMS: To analyse the intrahepatic macrophage activity in chronic HCV infection by immunostaining and by quantitation of cytokine mRNA. METHODS: HCV positive liver tissues (chronic hepatitis, n=10; cirrhosis, n=5) were immunostained for CD68, MAC387, and semiquantitated by polymerase chain reaction for intrahepatic cytokine mRNAs (interferon gamma (IFNgamma), interleukin 1beta (IL-1beta), IL-6, IL-18, tumour necrosis factor alpha (TNFalpha), and macrophage inflammatory protein 1beta (MIP1beta)). HCV negative normal liver tissues (for cytokines, n=6; for immunostaining, n=5) were included as controls. RESULTS: MAC387(+) cells were focally increased in areas of erosion at the limiting plate while lobular staining was minimal. CD68(+) staining was diffuse in both portal (increased in HCV) and lobular areas. The portal tract (mean) density of CD68(+) and MAC387(+) cells was significantly increased in patients with HCV compared with normal tissue. IFNgamma and IL-18 mRNA levels were highly correlated and significantly upregulated in chronic hepatitis and cirrhotic tissue versus controls. TNFalpha mRNA was upregulated in chronic hepatitis without cirrhosis, while IL-6 mRNA was significantly downregulated. IL-1beta, IL-6, and MIP1beta mRNA levels were significantly correlated with portal tract MAC387(+) cell density. CONCLUSIONS: The significant upregulation of IFNgamma and IL-18 mRNA and significant correlations between IFNgamma and other proinflammatory cytokines, suggest a Th1/cell mediated intrahepatic immune response in chronic HCV infection. However, further clarification of the cellular sources of these cytokines is required. (+info)
Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study.
(63/3013)
BACKGROUND/AIMS: A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. METHODS: Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. RESULTS: 130 patients had detectable iron at enrollment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). CONCLUSIONS: These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus. (+info)
Expression of matrix metalloproteinase-2 and -9 and their inhibitors in peripheral blood cells of patients with chronic hepatitis C.
(64/3013)
BACKGROUND: To clarify whether circulating matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) can be used as serum markers of fibroproliferation in chronic liver diseases, we studied the expression of MMP-2 and MMP-9 in relation to TIMP-1 and TIMP-2 in peripheral blood mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs), and compared this expression to circulating concentrations and hepatic histology in patients with chronic active hepatitis C (CAH). METHODS: Quantitative reverse transcription-PCR/ELISA assays were performed for MMP and TIMP RNA, and corresponding circulating protein concentrations were studied by ELISA in 20 healthy controls, 40 patients with CAH, and 20 patients with hepatitis C-induced cirrhosis (Ci). RESULTS: MMP-2 mRNA was found almost exclusively in the liver, MMP-9 mRNA in leukocytes. TIMP RNA-equivalents were decreased in MNLs of CAH patients, but neither MMP-9 nor TIMP RNA expression showed any correlation to the extent of inflammation and fibrosis. MMP-2 and TIMP-1 protein concentrations were increased in Ci patients and showed a wide overlap in CAH patients and healthy controls. MMP-9 values were lower in CAH and Ci patients than in healthy controls. TIMP-2 values showed a wide overlap in all three groups. The MMP-2/TIMP-1 and MMP-9/TIMP-1 ratios were lower in Ci patients than in healthy controls; the MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios were not different. Circulating TIMP-1 and the MMP-2/TIMP-1 ratio correlated to the inflammatory activity in liver biopsies, but only the circulating MMP-2/TIMP-1 ratio also correlated with the degree of fibrosis. CONCLUSIONS: Peripheral blood cell expression of MMP-2, MMP-9, and TIMP revealed no correlation with the circulating concentrations of these proteins. Only the circulating MMP-2/TIMP-1 ratio correlated to the histological degree of fibrosis in hepatitis C and should be further evaluated as a progression marker in patients with chronic liver disease. (+info)