Hepatic Hepatitis C Virus RNA as a Predictor of a Long-Term Response to Interferon-α Therapy

Shindo, Michiko; Arai, Ken; Sokawa, Yoshihiro; Okuno, Tadao

doi:10.7326/0003-4819-122-8-199504150-00005

Cited by 90 publications

(50 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…22 The long-term beneficial outcome of patients with chronic hepatitis C who have a biochemical and virological response to interferon-␣ has been documented in a number of studies from Europe and Asia. [23][24][25][26] In these studies, which provided an average follow-up of 2 to 5 years, relapses in disease were uncommon among patients who remained HCV RNA negative after therapy, the reported rate of relapses ranging from 4% to 6% in the two largest series. 25,26 Possible explanations for the occurrence of late relapses despite lack of HCV RNA 6 months after stopping therapy include reinfection caused by repeated exposure to hepatitis C, intermittent viremia combined with infrequency of testing, and unreliability of the PCR assay used to detect viral RNA at 6 months.…”

Section: Discussionmentioning

confidence: 99%

10-year follow-up after interferon-α therapy for chronic hepatitis C

et al. 1998

View full text Add to dashboard Cite

Sustained responses to interferon-␣ occur in 10% to 25% of patients with chronic hepatitis C, but the long-term outcome is not well defined. We evaluated the long-term clinical, histological, and virological outcomes of 10 patients with chronic hepatitis C who were treated between 1984 and 1987 with interferon-␣-2b for 52 ؎ 6 weeks (total doses of 492 ؎ 116 MU). Before therapy, all 10 had hepatitis C virus (HCV) RNA, elevations of serum aminotransferases, and chronic hepatitis with fibrosis on liver biopsy. Clinical follow up was 6 to 13 years, and liver biopsies were done 5 to 11 years after initiation of therapy. HCV RNA was assayed by qualitative and quantitative reverse transcriptase-polymerase chain reaction assays. Among 5 patients who had a 6-month sustained response after therapy, all remained HCV RNA negative, and at last follow-up, 4 had normal and 1 minimally elevated serum aminotransferase levels. Liver biopsy specimens were nonreactive for HCV RNA, and all the patients showed improvements in both inflammation and fibrosis and were either normal or had mild, nonspecific inflammatory changes. Among 5 patients without a sustained response, all continued to have HCV RNA in serum and persistent or intermittent aminotransferase elevations. Liver biopsy specimens showed little or no change in necrosis and inflammation; all except 1 patient had progression of fibrosis scores or cirrhosis. All 5 patients had symptoms of chronic hepatitis, 1 underwent liver transplantation, and another had progressive hepatic decompensation. In conclusion, patients with a 6-month posttreatment virological response have a favorable long-term clinical and histological outcome.(HEPATOL-OGY 1998;28:1121-1127.)Non-A, non-B hepatitis was recognized as the major cause of transfusion-associated hepatitis more than 20 years ago, when the discoverers of the hepatitis A virus showed that cases of viral hepatitis not related to hepatitis B were also not attributable to hepatitis A. 1 After more than a decade of intensive research, Houghton and co-workers isolated a fragment of the genome of the hepatitis C virus (HCV) and subsequently cloned and characterized this agent. 2

show abstract

Section: Discussionmentioning

confidence: 99%

10-year follow-up after interferon-α therapy for chronic hepatitis C

et al. 1998

View full text Add to dashboard Cite

show abstract

“…These results, together with the corresponding low ALT response rates among HCV RNApositive patients, confirm the clear relationship between sustained ALT normalization and clearance of HCV RNA that has recently been observed by others. 25,30 Conversely, the ALT responders who remained HCV RNA positive were likely to undergo clinical relapse in the year following IFN treatment. Further, the present data confirm that sustained ALT and viral response are associated with sustained improvement of liver inflammation and necrosis (but not fibrosis), as assessed histologically.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] IFN treatment improves liver histology 9,12,[16][17][18]21,22 and hepatic function, 6,23 and is associated with loss of HCV RNA from blood and liver in most responders. 14,16,18,[24][25][26][27][28][29][30] As a result of these findings, IFN has become an accepted treatment for hepatitis C. Unfortunately, the initial response is often not sustained. Specifically, 40% to 80% of cases exhibit ALT and viral relapse, usually within 24 weeks of completing treatment, so that only 8% to 25% of treated subjects have a sustained response (SR) to IFN-␣.…”

mentioning

confidence: 99%

Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: Results of an international randomized controlled trial

1998

View full text Add to dashboard Cite

The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-␣) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-␣n1 or recombinant IFN-␣2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-totreat analysis showed that ALT response at end of treatment was 35.3% for IFN-␣n1 and 37.9% for IFN-␣2b (P ‫؍‬ .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent Abbreviations: HCV, hepatitis C virus; ALT, alanine aminotransferase; IFN, interferon; SR, sustained response; HAI, Knodell' s Histological Activity Index; ETR, end-of-treatment response in ALT levels.From the

show abstract

“…Termination of the necro-inflammatory reaction after clearance of the underlying etiological factor(s) might result in improvement of liver fibrosis (1,(9)(10)(11)(12)(13)(14). In particular, IFN treatment has been clinically used for infected patients for over ten years in Japan.…”

Section: Discussionmentioning

confidence: 99%

Regression of Liver Fibrosis in Cases of Chronic Liver Disease Type C: Quantitative Evaluation by Using Computed Image Analysis

et al. 2004

View full text Add to dashboard Cite

Object It was reported that the liver fibrosis is reduced in patients with chronic liver disease type C after eradication of HCV. Degree of fibrosis was expressed by the classical fibrosis scoring system (F0-F4) at present. However a change of subtle reduction of fibrosis cannot be expressed in its fibrosis score and thus we measured an area of fibrosis and compared detailed change of the fibrosis area in paired liver biopsy.Methods For quantitative assessment of liver fibrosis, we measured an area of fibrosis using computed digital image analysis and pursued the rate of a fibrosis area for whole biopsied liver tissue of 25 patients with HCV infection (20 complete response patients to IFN therapy who showed viral eradication: CR and 5 non-treated ones with IFN but had conservative therapy: CT).Results In CR group, fibrosis rate was 7.2±1.5% before therapy, 2.7±0.5% after the therapy and they were significantly regressed. In CT group, fibrosis rate was 8.4±4.3% at the first biopsy, 15.9±7.7% at the second biopsy.Conclusions Regression of liver fibrosis could be confirmed in patients with virologic response to IFN even in patients with liver cirrhosis. Our quantitative evaluation provided information superior to that obtained by the classical fibrosis staging score system.

show abstract

Hepatic Hepatitis C Virus RNA as a Predictor of a Long-Term Response to Interferon-α Therapy

Cited by 90 publications

References 0 publications

10-year follow-up after interferon-α therapy for chronic hepatitis C

10-year follow-up after interferon-α therapy for chronic hepatitis C

Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: Results of an international randomized controlled trial

Regression of Liver Fibrosis in Cases of Chronic Liver Disease Type C: Quantitative Evaluation by Using Computed Image Analysis

Contact Info

Product

Resources

About