Future complications of chronic hepatitis C in a low-risk area: projections from the hepatitis c study in Northern Norway.

BACKGROUND: Hepatitis C (HCV) infection causes an asymptomatic chronic hepatitis in most affected individuals, which often remains undetected until cirrhosis and cirrhosis-related complications occur. Screening of high-risk subjects in Northern Norway has revealed a relatively low prevalence in the general population (0.24%). Despite this, late complications of HCV infection are increasing. Our object was to estimate the future prevalence and complications of chronic HCV infection in the period 2013-2050 in a low-risk area. METHODS: We have entered available data into a prognostic Markov model to project future complications to HCV infection. RESULTS: The model extrapolates the prevalence in the present cohort of HCV-infected individuals, and assumes a stable low incidence in the projection period. We predict an almost three-fold increase in the incidence of cirrhosis (68 per 100,000), of decompensated cirrhosis (21 per 100,000) and of hepatocellular carcinoma (4 per 100,000) by 2050, as well as a six-fold increase in the cumulated number of deaths from HCV-related liver disease (170 per 100,000 inhabitants). All estimates are made assuming an unchanged treatment coverage of approximately 15%. The estimated numbers can be reduced by approximately 50% for cirrhosis, and by approximately one third for the other endpoints if treatment coverage is raised to 50%. CONCLUSION: These projections from a low-prevalence area indicate a substantial rise in HCV-related morbidity and mortality in the coming years. The global HCV epidemic is of great concern and increased treatment coverage is necessary to reduce the burden of the disease.

Total and cause-specific mortality rates in a prospective study of community-acquired hepatitis C virus infection in northern Norway.

Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited. The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway. This prospective cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000, with a median observation time from diagnosis to follow-up of 7 years. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Time and cause of death were ascertained from the Norwegian Causes of Death Register. Age-adjusted death rates and standardised mortality ratios (SMRs) were compared with those of the general Norwegian population. In total, 122 deaths were recorded. The Kaplan-Meier estimate of survival was 88% at 14 years. The SMR in the cohort relative to the general population was 6.66. Most of the excess deaths in both genders were because of liver-related causes, those associated with a drug-using lifestyle and suicide. The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women. There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men. In conclusion, our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population.

A rapid chemokine response of macrophage inflammatory protein (MIP)-1α, MIP-1ß and the regulated on activation, normal T expressed and secreted chemokine is associated with a sustained virological response in the treatment of chronic hepatitis C.

The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial ß-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1ß, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1ß and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1ß, and RANTES response may predict a sustained response to virological treatment.

[Extrahepatic manifestations in hepatitis C. Are they overlooked?]. / Ekstrahepatiske manifestasjoner ved hepatitt C-infeksjon. Blir de oversett?

BACKGROUND: There are accumulating documentation of autoimmune mediated extrahepatic manifestations of hepatitis C virus infection. The virus is hepatotrophic and lymphotrophic. It mutates frequently with subsequent inadequate immune response and chronic stimulation of T and B cells. This may be one explanation for the increased frequency of the autoimmune diseases associated with hepatitis C virus infection. MATERIAL AND METHODS: In this review of the literature published in the period of 1990 to 2000, we present the most common extrahepatic manifestations of the hepatitis C virus infection. RESULTS: Mixed cryoglobulinaemia, membranoproliferative glomerulonephritis and membranous glomerulonephritis are highly associated with hepatitis C infection. Other autoimmune diseases may also be associated with hepatitis C infection, but further documentation is necessary. INTERPRETATION: Extrahepatic manifestations of hepatitis C virus infection are associated with several autoimmune diseases. When diagnosing an autoimmune disease, a test for a coinfection of hepatitis C is highly recommended. Antiviral therapy with interferon may in some cases reduce the activity of the autoimmune disease.