Background A region associated with sensitivity to interferon has been identified in the nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) genotype 1b. The region spans amino acid residues 2209 to 2248 (NS5A2209–2248) of HCV-J, a strain of HCV-1b whose complete genomic sequence has been identified. We examined whether the NS5A2209–2248 sequence present before therapy could be used as a predictor of the response to interferon therapy in patients with chronic HCV-1b infection. Methods We retrospectively analyzed 84 patients with chronic HCV-1b infection who had received interferon alfa (total dose, 516 million to 880 million units) for six months. Pretreatment serum samples were analyzed. The amino acid sequence of NS5A2209–2248 was determined by direct sequencing of the HCV genome amplified by the polymerase chain reaction (PCR) and was compared with the established sequence for HCV-J. Results A complete response, as evidenced by the absence of HCV RNA in serum on nested reverse-transcription PCR ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199601113340203

Mutations in the Nonstructural Protein 5a Gene and Response to Interferon in Patients with Chronic Hepatitis C Virus 1b Infection

Background End-stage cirrhosis related to hepatitis C virus (HCV) is a common reason for liver transplantation, although viremia is known to persist in most cases. We investigated the impact of persistent HCV infection after liver transplantation on patient and graft survival and the effects of the HCV genotype and the degree of HLA matching between donor and recipient on the severity of recurrent hepatitis. Methods A group of 149 patients with HCV infection who received liver transplants between January 1982 and April 1994 were followed for a median of 36 months; 623 patients without HCV infection who underwent liver transplantation for end-stage chronic liver disease were used as a control group. A total of 528 liver-biopsy specimens from the HCV-infected recipients were reviewed, including 82 obtained one year after transplantation as scheduled and 39 obtained at five years as scheduled. In addition, biopsy specimens were obtained from 91 of the HCV-negative patients five years after transplantation. R...

https://www.nejm.org/doi/pdf/10.1056/NEJM199603283341302

Long-Term Outcome of Hepatitis C Infection after Liver Transplantation

Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, an approach that provides guidance and tools to define the research questions, conduct the systematic review, assess the overall quality of the evidence, and determine strength of the recommendations. This report is intended to serve as a resource for health-care professionals, public health officials, and organizations involved in the development, implementation, and evaluation of prevention and clinical services. These recommendations will be reviewed every 5 years and updated to include advances in the published evidence.

/pdf/recommendations-for-the-identification-of-chronic-hepatitis-1z7424dxx8.pdf

Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965.

Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in the world and now ranks as the chief reason for liver transplantation in adults.1–3 Of the five known hepatitis viruses, three can cause persistent infection and chronic hepatitis: the hepatitis B virus (HBV),4 the hepatitis C virus (HCV),5 and the hepatitis delta (or hepatitis D) virus (HDV).6 The other two viruses, hepatitis A and hepatitis E, cause acute, self-limited disease only. Recent findings suggest that there is an additional form of viral hepatitis to which two recently discovered human viruses — the hepatitis . . .

The treatment of chronic viral hepatitis

A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies Factors associated with viral clearance were also examined Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C Information on study population, and factors that may influence viral clearance were extracted from each study Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated A total of 31 studies were examined Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases In total, data was available for 675 subjects and the mean study population was 22 (range 4-67) The proportion with viral clearance ranged from 00 to 08, with a weighted mean of 026 (95% CI 022-029) Factors associated with viral clearance were female gender and acute clinical hepatitis C study population Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies

Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies.

https://www.gastrojournal.org/article/0016-5085(93)91025-D/pdf

Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840150108

Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840170404

Hideki Hagiwara

Papers

Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy.

Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α

Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease.

Increased serum hepatitis C virus RNA levels among alcoholic patients with chronic hepatitis C

Serum hepatitis C virus RNA quantity and histological features of hepatitis C virus carriers with persistently normal ALT levels.