Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C

Bruno, Savino; Battezzati, Pier Maria; Bellati, G.; Manzin, Aldo; Maggioni, Marco; Crosignani, Andrea; Borzio, Mauro; Solforosi, Laura; Morabito, Alberto; Idéo, G.; Podda, Mauro

doi:10.1016/s0168-8278(01)00062-9

Cited by 73 publications

(68 citation statements)

References 32 publications

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“…The current analysis indicated that approximately two-thirds of all patients did not experience a change in fibrosis stage between paired biopsies. Because histologic improvement is a slow process, particularly for fibrosis, 4 it may be advisable to repeat liver biopsy 2 or 3 years after the end of treatment to assess the treatment benefit with respect to fibrosis. Due to the large number of patients analyzed in the current MIPD, we believe that a 'moderate' but clinically relevant treatment benefit with respect to liver fibrosis was not overlooked.…”

Section: Discussionmentioning

confidence: 99%

“…2 Liver histology provides direct evidence of hepatic necroinflammatory activity, fibrosis, and progression to cirrhosis, 3 and is a surrogate endpoint of the longterm efficacy of IFN treatment. 4 As a tool for evaluating response to treatment, histologic findings have several significant limitations and sources of bias. 5,6 For example, different scoring systems can be used to compare paired liver biopsies; in addition, biopsies may be performed at different times, and they may be evaluated by different pathologists in multicenter trials of antiviral therapy.…”

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confidence: 99%

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Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

et al. 2004

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Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, ؊0.14; 95% CI: ؊0.27, ؊0.01; P ‫؍‬ .04). A reduction in fibrosis was observed among sustained virologic responders (SMD, ؊0.59; 95% CI: ؊0.89, ؊0.30; P < .0001) and patients with recurrent disease (SMD, ؊0.34; 95% CI: ؊0.54, ؊0.14; P ‫؍‬ .0007), whereas no significant reduction was observed among nonresponders (SMD, ؊0.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

et al. 2004

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“…61 The rest of the studies, mostly retrospective and nonrandomized, suggested a moderate decrease in the risk for HCC among HCVinfected patients treated with interferon. 54,8,[62][63][64][65][66][67][68][69] In general, the reported preventive effect of interferon alfa therapy was less marked in European studies than in studies from Japan. The benefit was better appreciated in patients with sustained response than nonresponders.…”

Section: Hcc In Hcv-related Cirrhosismentioning

confidence: 99%

Hepatocellular carcinoma and hepatitis C in the United States

M.D.

2002

Hepatology

196

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Chronic infection with hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC). In general, HCC develops only after 2 or more decades of HCV infection and the increased risk is restricted largely to patients with cirrhosis or advanced fibrosis. Factors that predispose to HCC among HCV-infected persons include male sex, older age, hepatitis B virus (HBV) coinfection, heavy alcohol intake, and possibly diabetes and a transfusion-related source of HCV infection. Viral factors play a minor role. The likelihood of development of HCC among HCV-infected persons is difficult to determine because of the paucity of adequate long-term cohort studies; the best estimate is 1% to 3% after 30 years. Once cirrhosis is established, however, HCC develops at an annual rate of 1% to 4%. Successful antiviral therapy of patients with HCV-related cirrhosis may reduce the future risk for HCC. The incidence of and mortality caused by all HCC has doubled in the United States over the past 25 years, an increase that has affected all ethnic groups, both sexes, and younger age groups. Given the current prevalence of HCV infection among persons 30 to 50 years of age, the incidence and mortality rates H epatocellular carcinoma (HCC) affects approximately half a million persons each year worldwide making it the fifth most common malignancy in men and the ninth most common in women. HCC is a rapidly fatal cancer that mostly affects persons in developing countries where hepatitis B virus (HBV) is endemic. Recently, however, a trend of increasing rates of HCC has been reported from several developed countries in North America, Europe, and Asia. Hepatitis C virus (HCV) infection appears to play an important role in these new trends. Hepatitis C and HCCSeveral lines of evidence indicate a strong causal association between HCV and HCC. HCV RNA can be found in the serum, liver, and tumor tissues of patients with HCC, but unlike HBV it does not integrate into the host genome. 1 Markers of HCV infection are found in a variable proportion of HCC cases in Europe with an increasing gradient from North to South 2 ; for example, 44% to 66% in Italy, 3-5 27% to 58% in France, 6 60% to 75% in Spain, 7 and in 80% to 90% of HCC cases in Japan. 8,9 Moreover, the age-standardized death rates owing to HCC in several European countries are significantly correlated with the seroprevalence of HCV in the general population. 10 The frequency of HCV seropositivity among persons with HCC compiled from a summary of published studies of HCC in the United States is shown in Fig. 1. Of 1,429 patients assumed to have been tested, 384 (27%) were positive for HCV. 11-15 However, a higher but undefined proportion of patients with HCC might have had HCV detected by polymerase chain reaction testing of liver tissue and/or serum, even if antibody to HCV (anti-HCV) was not detectable, 16 particularly if first-generation tests were used. On the other hand, 240 of 1,670 (14%) patients with HCC in the United States tested positive for hepatitis ...

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“…Liver histology, evaluated by means of paired biopsies in HCV mono-infected patients, demonstrated an improvement in necroinflammation and even in fibrosis in those presenting SVR [7,8,13]. Stabilization of fibrosis has also been observed in non-responder patients after treatment with interferon-alpha [28], a fact that could be indicative of histological response since progression of fibrosis is expected to be the natural course of chronic hepatitis.…”

Section: Discussionmentioning

confidence: 96%

“…PEGylated or non-PEGylated interferon-alpha in combination with ribavirin, the recommended treatment for chronic hepatitis C, can promote a sustained virological response (SVR) in a considerable number of patients and, in some cases reduce the liver inflammatory and fibrotic processes [4,5]. In addition, some studies have shown that treatment with interferon-alpha leads to improved liver histology, mainly reducing inflammation and having a lesser effect on fibrosis [6], especially in patients who show a sustained virological response [7,8]. On the other hand, the influence of the treatment on the improvement of hepatic histology in patients who do not have SVR has shown controversial results [9][10][11][12][13].…”

Section: It Is Known That Human Immunodeficiency Virus (Hiv) May Modimentioning

confidence: 99%

HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

Castro¹,

Ramalho²,

Zucoloto³

et al. 2008

Braz J Infect Dis

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Liver histological improvement after treatment for chronic hepatitis C in patients co-infected with human immunodeficiency virus-1 (HIV-1) has been described. Paired liver biopsies in twenty six HCV/HIV co-infected patients were compared to determine factors possibly associated with histological improvement. The patients were submitted to a liver biopsy before treatment for hepatitis C and 25 months after the end of treatment. Fragments of the liver biopsy obtained before and after treatment were compared regarding the following parameters: histological activity index (HAI) and degree of fibrosis (Knodell); intensity of collagen deposits (Sirius Red staining) and degree of stellate cell activation (alpha-smooth muscle actin labeling). The ratios of the post and pre-treatment variables were related through logistic regression to body mass index (BMI), alcohol ingestion, HCV genotype, HCV viremia, presence of hepatic iron and pre-treatment hepatic steatosis. A negative RNA test in the 24 th week of treatment was associated with improvement in fibrosis, collagen deposits and stellate cell numbers. The other variables analyzed did not correlate to an improvement in hepatic histology after hepatitis C treatment. Reduction in HCV viremia during treatment may result in reduced hepatic fibrosis even in patients without a sustained virological response.

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Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C

Cited by 73 publications

References 32 publications

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data

Hepatocellular carcinoma and hepatitis C in the United States

HCV virological response during treatment of chronic hepatitis C is associated with liver histological Improvement in patients with HCV/HIV co-infection

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