Lesions In Chronic Hepatitis Research Articles

Differential gene expression between chronic hepatitis B and C hepatic lesion

Background & Aims: Complementary DNA (cDNA) microarray technology allows simultaneous expression analysis of hundreds to thousands of genes. We applied the cDNA microarray technique to clarify gene expression profiles in chronic viral hepatitis tissue lesions. Methods: We made cDNA microarrays consisting of 1080 human cDNAs and analyzed gene expression using labeled cDNAs prepared from 6 normal, 12 chronic hepatitis B, and 14 chronic hepatitis C liver tissues. Relative expression ratios of individual genes were obtained by comparing hybridization of Cy5-labeled cDNAs from chronic hepatitis lesions and Cy3-labeled cDNA from normal liver tissue. Results: Hierarchical clustering analysis of the gene expression profiles in 26 patients showed that the patients were clustered into 2 groups with respect to similarities in differentially expressed genes. Hepatitis B and C virus infection, but not age, sex, or histology of hepatitis, were significant factors determining clustering (P < 0.05). In hepatitis B tissue lesions, genes involved in inflammation were predominant, whereas in hepatitis C, expression of anti-inflammatory response genes was relatively dominant. Conclusions: These findings shed new light on the possible differential molecular mechanisms in the pathogenesis of hepatitis caused by hepatitis B virus and hepatitis C virus infection, from which hepatocellular carcinoma frequently develops.GASTROENTEROLOGY 2001;120:955-966

Bile duct lesions in chronic hepatitis C: Biochemical and virological relationships with histological damage

Bile duct lesions in chronic hepatitis C: Biochemical and virological relationships with histological damage

Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C.

The role of alcohol intake in the occurrence of severe liver disease in chronic hepatitis C virus (HCV) carriers is still debated. A cross-sectional study has been conducted in 233 chronic hepatitis C virus carriers. Weekly self-reported alcohol consumption (SRAC) was evaluated, serum HCV RNA levels were measured by a branched DNA technique (Quantiplex 2.0) and HCV genotypes were determined. A liver biopsy was performed simultaneously and liver lesions were graded with the Knodell histological activity index. Data were examined by uni- and multivariate analyses. Alcohol consumption was relatively low (< 140 g/per week in 193/233 patients [80%]). We found a highly significant correlation between SRAC and serum HCV RNA levels (r = .26, P = .001). Fibrosis was significantly correlated with age and alcohol consumption. These results suggest that in HCV carriers, alcohol consumption, even with low alcohol intake, increases viremia and hepatic fibrosis. Chronic HCV carriers should be advised to avoid regular alcohol intake.

Influence of the transmission route and disease duration in the histopathology of chronic hepatitis C: a study of 101 patients.

Different studies have demonstrated that factors such as transmission route, disease duration and age at the time of infection can influence the histological evolution of chronic hepatitis by the hepatitis C virus (HCV). The aim of this study was to determine if epidemiological factors such as disease duration and transmission route influence the severity of the histological lesions of patients with chronic hepatitis by HCV. A prospective study. The hepatic biopsies of 101 patients diagnosed with chronic hepatitis by HCV were studied. The patients were divided into three groups according to transmission mode: (1) post-transfusional (n = 28), (2) associated with the use of drugs by parenteral route or intravenous drug use (n = 28), and (3) sporadic hepatitis (n = 45). We found more severe forms of hepatopathy in post-transfusional hepatitis and sporadic groups than in the intravenous drug user group of patients. The disease evolution time was significantly higher in patients diagnosed as having chronic active hepatitis with or without cirrhosis (13.8 +/- 9 years) than in patients with chronic persistent hepatitis (8 +/- 4 years), P < 0.01. We found a significant correlation between the evolution time of the infection by HCV and the Histology Activity Index (P < 0.01). The multivariate analysis showed that only the transmission route and the disease evolution time are predictive variables of Histology Activity Index in chronic hepatitis C. These results suggest that the post-transfusional and sporadic transmission routes and a greater evolution time of the disease are epidemiological variables that are associated with the presence of more severe histological lesions in chronic hepatitis C.

Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C.

Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated the occurrence and progression of oral lesions in chronic hepatitis C patients treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men, nine women; mean age 48.1 years) for oral lesions before, during and after interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had OLP before treatment, one during and one after treatment. Those who developed OLP during or after treatment had neither improvement nor disappearance of OLP even when serum HCV RNA became negative. Leucoplakia was seen in four patients before treatment and oral cancer in one patient 6 months after completing treatment. OLP can occur, exacerbate and persist during IFN treatment for hepatitis C, even when serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis in hepatitis C is due to host factors induced by HCV infection rather than direct HCV participation. Treating physicians should be aware of OLP occurrence or exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not necessarily contraindicated in these patients.

The long-term pathological evolution of chronic hepatitis C

Most patients infected with hepatitis C virus (HCV) develop chronic hepatitis. Unfortunately, the pathological evolution of this disease over time is not completely understood. We studied 70 HCV-positive patients, from whom 2 to 10 liver biopsy specimens (mean, 3.9) had been obtained during an interval of 1 to 26 years (mean, 8.8 years). Each biopsy specimen was evaluated independently by four pathologists who each provided a numerical score for the grade of portal/periportal necroinflammation (0-4), grade of lobular necroinflammation (0-4), their sum (final grade), and the stage of fibrosis (1-4). The scores were correlated with progression of disease, if any, and transition to cirrhosis. During follow-up, 35 patients (50%) developed cirrhosis. Cirrhosis developed in all patients with a high final grade (> or = 5) of necroinflammation on initial biopsy who were followed for 10 years and in 96% of patients with an intermediate final grade (3.5-4.9) who were followed for 17 years. Only 30.4% of patients with low final grade (< or = 3.4) on initial biopsy developed cirrhosis after 13 years. All patients with evidence of septal fibrosis with incomplete nodularity (stage 3.0-3.4) in the initial biopsy progressed to unequivocal cirrhosis by 10 years. The rate of progression to cirrhosis was accelerated in patients whose initial biopsies showed high-grade and -stage lesions. This study demonstrates the importance of grading and staging liver biopsy lesions in chronic hepatitis C, particularly for patients with high-grade necroinflammation, septal fibrosis, and regions of modularity on initial biopsy who are at high risk of developing advanced cirrhosis in the ensuing decade. (Hepatology 1996 Jun;23(6):1334-40)

The long-term pathological evolution of chronic hepatitis C.

Most patients infected with hepatitis C virus (HCV) develop chronic hepatitis. Unfortunately, the pathological evolution of this disease over time is not completely understood. We studied 70 HCV-positive patients, from whom 2 to 10 liver biopsy specimens (mean, 3.9) had been obtained during an interval of 1 to 26 years (mean, 8.8 years). Each biopsy specimen was evaluated independently by four pathologists who each provided a numerical score for the grade of portal/periportal necroinflammation (0-4), grade of lobular necroinflammation (0-4), their sum (final grade), and the stage of fibrosis (1-4). The scores were correlated with progression of disease, if any, and transition to cirrhosis. During follow-up, 35 patients (50%) developed cirrhosis. Cirrhosis developed in all patients with a high final grade (> or = 5) of necroinflammation on initial biopsy who were followed for 10 years and in 96% of patients with an intermediate final grade (3.5-4.9) who were followed for 17 years. Only 30.4% of patients with low final grade (< or = 3.4) on initial biopsy developed cirrhosis after 13 years. All patients with evidence of septal fibrosis with incomplete nodularity (stage 3.0-3.4) in the initial biopsy progressed to unequivocal cirrhosis by 10 years. The rate of progression to cirrhosis was accelerated in patients whose initial biopsies showed high-grade and -stage lesions. This study demonstrates the importance of grading and staging liver biopsy lesions in chronic hepatitis C, particularly for patients with high-grade necroinflammation, septal fibrosis, and regions of modularity on initial biopsy who are at high risk of developing advanced cirrhosis in the ensuing decade.

Prolonged treatment (18 months) of chronic hepatitis C with recombinant α-interferon in comparison with a control group

The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units until the eighteenth month). Retrospectively, 26 patients had anti-hepatitis C antibodies. After the first month, 40% of the treated patients had normal serum alanine aminotransferase levels, and no one in the control group (p less than 0.05). After 18 months of treatment, 40% (6/15) of treated patients and 7% (1/14) of controls had normal serum transaminases (p less than 0.05). Interferon was well tolerated. A decrease in the Knodell Index score on final biopsy was found in treated patients (p less than 0.05), with no variations in the control group. Relapse within 7 months after the end of treatment occurred in two out of six complete responders. Thus, recombinant alpha-interferon therapy given for 18 months normalizes serum transaminases and improves histological lesions in chronic hepatitis C of parenteral epidemiology. This long-term interferon schedule is well tolerated.