Search PubMed⌕ Search

Biomedical subjects

P Marcellin

Publications and source records attributed to P Marcellin.

At least 73 records · Page 4Linked to original sources
PubMed1999

Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.

To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.

Adolescent↗
PubMed1999

Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP).

Interferon alfa (IFN-alpha) is the primary treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-alpha treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in which all patients were treated with a standard regimen of 10 million units IFN-alpha 3 times per week over 16 weeks. Patients who were still HBeAg-positive after 16 weeks of therapy were randomized to prolongation of the identical regimen up to 32 weeks (prolonged therapy) or discontinuation of treatment (standard therapy). Among the 162 patients who entered the study, 27 (17%) were HBeAg-negative after the first 16 weeks of treatment, and 118 were randomized to standard or prolonged therapy. After randomization, a response (HBeAg seroconversion and sustained hepatitis B virus [HBV]-DNA negativity) was observed in 7 of the 57 (12%) patients assigned to standard therapy versus 17 of the 61 (28%) patients assigned to prolonged therapy (P =.04). A low level of viral replication after 16 weeks of treatment, as indicated by serum HBV-DNA values under 10 pg/mL, was found to be the only independent predictor of response (52% vs. 0%; P <.001) during prolonged therapy. The prolonged IFN-alpha schedule was well tolerated in the large majority of patients. In chronic hepatitis B, prolongation of IFN-alpha therapy up to 32 weeks is superior to a standard course of 16 weeks. Those patients who exhibit a low level of viral replication at the end of the standard regimen benefit most from prolonged treatment.

Adolescent↗
PubMed1999

Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.

Adolescent↗
PubMed1999

Chronic hepatitis C: interferon retreatment of relapsers. A meta-analysis of individual patient data. European Concerted Action on Viral Hepatitis (EUROHEP).

Relapse after interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection occurs in 50% of patients after the initial response. The benefit of retreatment with IFN alone has not been assessed in large controlled studies. To assess the effectiveness and the tolerability of IFN retreatment and to identify the optimal second course regimen, we performed a meta-analysis of individual patient's data on a set of 549 patients (mean age 43.8 years; 12.2 SD, men: 65%) who had an end-of-treatment biochemical response to a first IFN course and then relapsed. Retreatment was started within 24 months after the end of the first course. Biochemical end-of-treatment responses (ETR) and sustained responses (SR) were observed in 405 of 549 (73.8%; 95% confidence interval [CI] 70.1-77.5) and in 124 of 549 (22.6%; CI 19.1-26.1) patients, respectively. One hundred seventy-five of 404 patients (43.3%; CI 38.6-48.2) developed an end-of-treatment, biochemical, and virological response when retreated. A biochemical and virological SR to retreatment occurred in 73 of 494 (14.8%; CI 11.7-18) patients. Thirty-two patients (5. 8%; CI 3.5-7.8) stopped retreatment for adverse effects. Biochemical and virological SR was predicted independently by logistic regression analysis using a negative HCV RNA at the end of the first cycle of IFN (P =.01) and by retreatment with a high IFN dose (P =. 03). Age, cirrhosis, genotype, and gamma-glutamyl transferase levels before retreatment were not significant by multivariate analysis. The excellent tolerability of IFN monotherapy retreatment makes it an option for patients who transiently cleared HCV-RNA during their first IFN course. Patients should be retreated with a high IFN dose regardless of the strength of the dose received during the previous course of treatment.

Adult↗
PubMed1999

Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

OBJECTIVES: To utilize cytokine levels to predict sustained response (SR) to alpha interferon (IFN alpha) therapy in chronic hepatitis C patients, and to determine the relationship between serum tumor necrosis factor alpha (TNF alpha), interleukin (IL) IL 6, IL 8, IL 12, transforming growth factor beta (TGF beta 1) and the degree of liver damage as reflected by traditional markers. DESIGN AND METHODS: Serum cytokine levels were assessed using ELISA in 18 patients included in a controlled clinical trial of IFN alpha. RESULTS: Of the 18 patients, 27% were sustained responders (SR), 27% were response and relapse responders (RR), and 46% were non-responders (NR). Multivariate analysis showed that a low serum TNF alpha level and high serum IL 8 levels were independent factors associated with SR to IFN alpha therapy. Serum TNF alpha level highly correlated with viral load and genotype predictive values (p < 0.001). Therapy lowered the IL 6 and IL 12 profile. TGF beta 1 levels in serum are positively correlated with fibrinogenesis. CONCLUSIONS: IFN alpha therapy modulates immune response to hepatitis C virus, contributing to sustained response.

Adult↗
PubMed1999

Quantification of hepatitis C virus RNA in serum by branched DNA-based signal amplification assays.

The objective of the study was to compare the clinical sensitivity and specificity of versions 1.0 and 2.0 of the branched DNA (bDNA)-based hepatitis C virus (HCV) RNA quantification assay, and also to compare the values yielded by the two versions according to the HCV genotype. Serum samples from 268 patients tested routinely by a non-quantitative HCV RNA PCR assay (group A) were tested with version 2.0 of the bDNA assay. Samples from 342 HCV PCR-positive patients with chronic hepatitis C eligible for interferon treatment (group B) were tested with both version 1.0 and version 2.0 of the bDNA assay. Version 2.0 had a clinical sensitivity of 92% (95% confidence interval (CI): 87-97%) in group A and 89% (86-92%) in group B. In group B, the gain in sensitivity with bDNA 2.0 was 16% relative to bDNA 1.0 (P < 0.001). The log values of the two assays correlated with samples positive by both assays (r = 0.83, P < 0.0001), but the distribution of values was larger in samples containing HCV genotypes 2 and 3. The mean ratio of assay 2.0/assay 1.0 values was 1.69 +/- 1.44 (range: 0.33-13.43). The mean ratio was close to 1 with samples containing genotype 1 or 4, but ranged from 0.33 to more than 5. The mean ratio was close to 3 with samples containing genotype 2 or 3, and ranged from 0.5 to more than 13. HCV RNA levels were significantly lower in samples containing genotype 4 than in those containing other genotypes. Sera from 200 anti-HCV-negative, HCV RNA PCR-negative blood donors (group C), and from 164 anti-HCV-negative patients with symptoms of chronic liver disease (group D) were used to assess the clinical specificity of bDNA 2.0. In addition, samples with an HCV RNA titer between 0.2 (assay cutoff) and 0.5 MEq/ml from a group of 546 patients tested routinely for HCV RNA load by bDNA 2.0 (group E) were retested by bDNA 2.0 and by qualitative PCR. The specificity of bDNA 2.0 was 100% (98-100%) in group C and 99% (97-100%) in group D. Among the 41 samples from group E, 38 were positive by bDNA 2.0 retesting (36 were PCR-positive) and three were negative by bDNA 2.0 retesting (all were PCR-positive). It is concluded that version 2.0 of the bDNA assay is markedly more sensitive than version 1.0 and has a good specificity. In contrast with version 1.0, version 2.0 is not influenced by the HCV genotype. The relationship between values obtained with assays 1.0 and 2.0 on clinical specimens is not linear, indicating that HCV RNA titers cannot reliably be calculated from the results of version 1.0.

DNA, Viral↗
PubMed1999

Hepatitis C: the clinical spectrum of the disease.

The hepatitis C virus (HCV) infects nearly 170 million people worldwide and is responsible for approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis. Acute hepatitis is icteric in only 20% of patients and is rarely severe. Eighty-five percent of infected patients develop chronic infection which is generally asymptomatic, resulting in most cases in fortuitous diagnosis, which may be made at a late stage. Twenty-five percent of the HCV chronic carriers have persistently normal serum alanine aminotransferase (ALT) levels despite having detectable HCV RNA in serum; 75% have elevated ALT levels. The former patients usually have mild histologic lesions, probably with a good long-term prognosis. In the latter patients, a liver biopsy is the most accurate way to distinguish patients with mild chronic hepatitis from those with moderate or severe chronic hepatitis. While most patients with mild chronic hepatitis have a slowly progressive liver disease, the patients with moderate or severe chronic hepatitis may develop cirrhosis within a few years. In patients with HCV-related cirrhosis, the incidence of hepatocellular carcinoma is 2-5% per year. At presently, HCV-related end-stage cirrhosis is the first cause of liver transplantation.

Acute Disease↗
PubMed1999

Treatment of hepatitis C patients with normal aminotransferases levels.

An important subset of patients with chronic hepatitis C have normal ALT levels despite having detectable HCV RNA in serum. These patients are typically identified after donating blood and being found positive for antibody to HCV (anti-HCV). A strict definition of this patient population is needed, which should include the presence of anti-HCV, detectable HCV RNA by PCR and persistently normal ALT levels. These patients are usually asymptomatic, but on liver biopsy almost all have histologic evidence of chronic hepatitis. The histologic findings generally are mild, and cirrhosis is rare. The long-term outcome of this group of patients with chronic HCV infection is not known, but the prognosis is probably good. In small, uncontrolled trials of IFN-alpha in patients with normal ALT levels, end-of-treatment virologic responses occurred in 42% of patients, and sustained responses 6 to 12 months afterwards in 13% of patients. These rates of response are not very different from those reported in patients with elevated ALT levels. Importantly, in most studies, serum ALT levels became elevated during IFN therapy in approximately one half of patients, and levels remained elevated in some of these patients after therapy. These findings suggest that IFN-alpha therapy is not usually beneficial and may be harmful in chronic hepatitis C patients with normal ALT levels. Combination therapy with IFN and ribavirin has not been evaluated in this group of patients.

Alanine Transaminase↗
PubMed1999

Hepatitis C virus genotypes in France: relationship with epidemiology, pathogenicity and response to interferon therapy. The GEMHEP.

The aim of this study was to investigate the following in a large population of French patients with chronic hepatitis C: the geographical distribution of hepatitis C virus (HCV) genotypes; the relationship between HCV genotypes and epidemiological characteristics; severity of the disease; and response to interferon (IFN) therapy. Data from 14 tertiary referral centres, corresponding to 1872 patients with chronic hepatitis C, were prospectively collected from 1989 to 1997. HCV genotyping was performed using the line probe assay (LiPA). HCV genotypes 1b, 3, 1a, 2, 4 and a mixed infection were found in 41%, 22%, 16%, 11%, 4% and 4% of our population, respectively. HCV genotype distribution was homogeneous, except for genotype 2 that was found more frequently in the southwest than in the other regions (21% vs 9.2%) (P=0.001). HCV distribution was associated with gender, age, and source and duration of infection. In multivariate analysis, these correlations were related to the source of infection, which was the only independent factor significantly associated with genotype (P=0.001). Genotype 1b was significantly more common in patients with cirrhosis, but in multivariate analysis cirrhosis was independently related to older age at exposure and longer duration of infection (P=0.001). A sustained response to IFN therapy was observed in 11% of patients infected with genotypes 1a or 1b vs 32% of those infected with genotypes 2 or 3 (P=0.001). This study shows that HCV genotype is mainly related to the source infection, but not to the intrinsic pathogenicity of HCV, and is a strong predictor of sustained response to therapy.

Adult↗
PubMed1999

Mesalazine (5-aminosalicylic acid) induced chronic hepatitis.

BACKGROUND: Treatment of ulcerative colitis or Crohn's disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported. CASE REPORT: A 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration. CONCLUSION: Contrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.

Aged↗
PubMed1998

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.

Administration, Oral↗
PubMed1998

[Pretreatment with prednisolone enhances the effect of human lymphoblastoid interferon in chronic hepatitis B].

Patients (n = 213) with chronic hepatitis B were randomised to prednisolone (two weeks of 0.6 mg/kg/day, one week of 0.45 mg/kg/day and one week of 0.25 mg/kg/day) or placebo followed by two weeks rest, and were then given human lymphoblastoid interferon 10 MU daily for five days followed by 10 MU thrice weekly for 11 weeks. There were statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). HBeAg disappearance and HBeAg to anti-HBe seroconversion rates were 28 vs. 44% and 23 vs. 38% (placebo vs. prednisolone). Fifteen patients (7.5%) lost HBsAg. Three out of 22 cirrhotic patients (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome. Prednisolone pre-treatment, enhances the effect of lymphoblastoid interferon in chronic hepatitis B. Interferon treatment (with and without prednisolone) should be used with caution in patients with cirrhosis and avoided in patients with evidence of hepatic decompensation.

Adult↗
PubMed1998

Re-treatment with interferon alfa of patients with chronic hepatitis C.

Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

BACKGROUND/AIMS: The aim of this study was to determine the predictors for sustained response to alpha interferon therapy in a large population of patients with chronic hepatitis C, using multivariate analysis. METHODS: Two hundred and ninety-six patients were included in four controlled trials of alpha interferon. Pretreatment serum HCV RNA levels were assessed by the branched DNA version 2.0 assay and HCV genotypes by the reverse hybridization assay (LiPA). RESULTS: Sustained responses were observed in 37%, 14% and 6% of the patients with low, medium and high pretreatment serum HCV RNA levels, respectively (p<10(-4)). Sustained responses were observed in 5%, 4%, 32% and 27% of the patients with genotype 1a, 1b, 2a and 3a, respectively (p<10(-4)). The multivariate analysis showed that a non-transfusional source of HCV infection, low serum HCV RNA levels and HCV genotypes non-1 (2a or 3a) were independent factors associated with sustained response to interferon therapy. CONCLUSION: Virological factors (low pretreatment serum HCV RNA level and HCV genotype non-1a and non-1b), when adjusted in a large population of patients, using improved technology, are the main independent predictors of sustained response to alpha interferon therapy.

Adult↗
PubMed1998

Changes in liver fibrosis at the end of alpha interferon therapy and 6 to 18 months later in patients with chronic hepatitis C: quantitative assessment by a morphometric method.

BACKGROUND/AIMS: The aims of the study were to determine, in patients with chronic hepatitis C treated with alpha interferon: (i) changes in the morphometric evaluation of liver fibrosis at the end of treatment and 6, 12 and 18 months after treatment; (ii) the predictive value of histologic lesions for the response to treatment, in particular the predictive value of morphometric evaluation of liver fibrosis. METHODS: Seventy patients with chronic hepatitis C who participated in two trials of recombinant interferon alpha 2b treatment were studied. Liver specimens were obtained before and at the end of treatment and 6, 12 or 18 months later. Histologic lesions were assessed according to the Knodell system. Quantitative study of total fibrosis and of Disse space collagen was done by the computerized automated morphometric method. RESULTS: A significant decrease in morphometric Disse space collagen was observed at the end of treatment and 6 months later. This decrease was also observed, although it was not significant, 12 and 18 months after treatment. There was no relationship between this decrease and the biochemical and virological responses or the dose of interferon. The pretreatment Knodell activity score, but not the morphometric evaluation of fibrosis, was a significant predictor of sustained response. CONCLUSION: A decrease in Disse space collagen, as assessed by the sensitive morphometric method, was observed at the end of and 6 months after treatment. This observation is consistent with an anti-fibrogenetic effect of alpha interferon. Mild or moderate histologic activity was associated with a sustained response to therapy.

Antiviral Agents↗