Viral clearance in HCV viraemic patients with normal alanine aminotransferase after combination therapy: a controlled, open-labelled study.

BACKGROUND: In patients with chronic hepatitis C virus infection and persistently normal alanine aminotransferase levels, liver fibrosis has been reported in 0-22% of cases and advanced liver disease in 5-10% of cases. AIM: To determine whether patients with persistently normal alanine aminotransferase levels clear infection after anti-viral therapy at equal or different rates from infected patients with raised alanine aminotransferase levels. METHODS: Thirty-five hepatitis C virus RNA-positive patients with fibrosis at liver histology (Group 1) were matched for genotype, sex, age and histology with patients with raised alanine aminotransferase levels (Group 2). Both groups were treated with 3 MU interferon-alpha2b plus ribavirin (1000-1200 mg) for 12 months. RESULTS: End-of-therapy response was achieved in 71.4%[95% confidence interval (CI), 56.4-86.3] of patients in Group 1 and in 52.3% (95% CI, 42.8-61.9) of those in Group 2 (P = 0.04). At week 72, 22 patients (62.8%; 95% CI, 46.8-78.1) in Group 1 and 50 patients (47.5%; 95% CI, 38.0-57.1) in Group 2 showed a sustained virological response (P = 0.11). Non-1 genotype was the only independent predictor of sustained response (P = 0.002), with an odds ratio of 3.45 (95% CI, 1.58-7.50). At month 3 of therapy, the positive predictive values for non-response were 100% and 96% in Groups 1 and 2, respectively. CONCLUSIONS: Interferon and ribavirin induce comparable sustained virological response in patients with persistently normal or raised alanine aminotransferase levels. Stage 1 fibrosis, rather than alanine aminotransferase levels, may be the criterion on which to decide whether or not to treat patients with persistently normal alanine aminotransferase levels.

[Clinical and etiologic features of hepatocarcinoma in Sicily]. / Aspetti clinici ed etiologici dell'epatocarcinoma in Sicilia.

Hepatocellular carcinoma is a neoplasia with a high degree of malignancy and a quite unfavorable prognosis, and its frequency has tripled over the last 30 years. The aim of this study was to shed further light on some epidemiological and clinical aspects of hepatocellular carcinoma, on the basis of experience with a wide ranging patient population. We included 179 patients (127 males, 52 females, age range 31-86 years), diagnosed with hepatocellular carcinoma between January 1993 and December 1998. For each patient we recorded age, sex, coexistence and cause of cirrhosis, severity of cirrhosis, stage of hepatocellular carcinoma, serum markers of viral hepatitis (hepatitis B surface antigen and hepatitis C virus antibodies) and serum levels of alpha-fetoprotein. Hepatocellular carcinoma was associated with hepatitis C virus in 72% of patients, with hepatitis B virus in 10%, with combined infection in 3% and with negative viral markers in 15%. Mean age at diagnosis was significantly higher in the hepatitis C virus infection patients than in the combined infection patients (p < 0.04); the male/female ratio was 2.1:1 in the hepatitis C virus and 8:1 in the hepatitis B virus subjects. At hepatocellular carcinoma diagnosis, 175 out of 179 patients had liver cirrhosis with a significantly higher severity in patients with negative viral markers than in those with positive viral markers (p < 0.02). The stage of hepatocellular carcinoma at diagnosis was very advanced: in 103 out of 179 cases (58%) neoplasia was stage IV, with a stage I diagnosis in only 14 out of 179 (8%) cases. All the combined (hepatitis B and C virus) cases were diagnosed at stage IV, while hepatocellular carcinoma cases in patients with negative viral markers were diagnosed at earlier stages (66% stages I-II). Serum alpha-fetoprotein levels were above the normal limit (20 ng/mL) in 72% of patients; however, only 30% (54/179) had alpha-fetoprotein values > 400 ng/mL. These data confirm some previous epidemiological and clinical evidence concerning hepatocellular carcinoma (mean age at diagnosis, male/female ratio, severity of pre-existing liver disease, frequency of an associated hepatitis C and/or hepatitis B virus infection). Data based on such a large population, moreover, aid clarification of some still unresolved points such as the utilization of alpha-fetoprotein values in diagnosing hepatocellular carcinoma.

Acetylcysteine therapy for chronic hepatitis C: are its effects synergistic with interferon alpha? A pilot study.

OBJECTIVE: This trial reports the 6-month results of a pilot study using lymphoblastoid interferon alpha (IFNalpha) and acetylcysteine (N-acetylcysteine) separately and in combination in patients with chronic hepatitis C, genotype 1b, who were nonresponders to previous treatment with recombinant IFNalpha alone. PATIENTS AND METHODS: 21 patients were randomly divided into three groups of seven each. Group A was treated with lymphoblastoid IFNalpha 6MU three times a week for 6 months; group B received the same schedule of lymphoblastoid IFNalpha as group A plus acetylcysteine 1200 mg/day per os in two administrations, and group C received only acetylcysteine 1200 mg/day per os in two administrations. RESULTS: Mean serum alanine aminotransferase (ALT) levels at 6 months in groups A and B, but not in group C, were significantly lower than baseline values (p < 0.05 and p < 0.03, respectively). Two patients in group A (28.6%) and three in group B (42.9%), but none in group C, had normalised ALT levels at 6 months. During follow-up, levels flared in one group A and in one group B patient. Thus, at the end of follow-up one group A and two group B patients were sustained responders. At the end of therapy and follow-up, hepatitis C virus (HCV)-RNA was negative in one patient in group A and two patients in group B. As no serious adverse effects were observed, therapy was never interrupted or suspended. CONCLUSION: Acetylcysteine alone had no effect on hepatic cytolysis and viral replication; lymphoblastoid IFNalpha showed a modest, but better, response than recombinant IFNalpha, and the combination therapy, although in a limited number of patients, appeared to be more efficient than lymphoblastoid IFNalpha alone.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

BACKGROUND/AIM: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center. PATIENTS: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al. RESULTS: Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR. CONCLUSIONS: This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.

Randomised Trial of Two Different Daily Doses of Interferon-α versus Classical Therapy in Treatment-Naïve Patients with Chronic Hepatitis C.

OBJECTIVE: To evaluate the efficacy and tolerability of two different daily doses of interferon-α (lymphoblastoid-IFNα-N1, Wellferon®) [IFNα] for 2 months, followed by the same dose on alternate days for up to 1 year, versus administration on alternate days for 1 year. PATIENTS AND METHODS: A non-blind, randomised study of outpatients with chronic hepatitis C at five centres in Sicily, Italy. Ninety-seven consecutive treatment-naive patients [72 patients with hepatitis C virus (HCV) genotype 1b infection] with histological chronic hepatitis C were included in the study and randomised to receive IFNα subcutaneously: 5 million international units (MIU) daily for 2 months, followed by the same dose on alternate days for up to 1 year (n = 33, group A); 3 MIU for 2 months, followed by the same dose on alternate days for up to 1 year (32, group B); 5 MIU on alternate days for 12 months (32, group C). Adverse effects were monitored through interviews and by clinical and biochemical check-ups at 1-month intervals. RESULTS: There were no significant differences between the three groups with regard to age, gender, HCV genotype distribution, or severity of histological findings. Seven patients dropped out of the study because of severe adverse effects: three from group A, two from group B, and three from group C. Approximately 30% of the 97 patients, equally distributed between the three groups, had a 'flu-like syndrome of mild-to-moderate intensity. Dosage reduction of IFNα from 5 MIU to 3 MIU daily was necessary in two patients in group A during the first month of treatment. Overall, 88 patients completed treatment as scheduled. After the induction phase, HCV was eradicated from the bloodstream in 27 patients (81.8%) from group A versus 15 (46.9%) from group B (p < 0.001) and 15 (46.9%) from group C (p < 0.001). The switch to maintenance dosages caused some infection breakthroughs, with the result that at the end of treatment 16 patients in group A, 12 in group B and 14 in group C had undetectable serum levels of HCV-RNA. After treatment discontinuation, however, five patients in group A, four in group B and six in group C became HCV-RNA positive. Thus, at the end of follow-up, 11 patients in group A, eight in group B and eight in group C had a sustained virological response. CONCLUSION: The present study shows that induction therapy with 5 MIU of IFNα administered daily for 2 months is well tolerated and that the percentage of patients with viral eradication at the end of this phase is higher than the percentage obtained with traditional therapy. Unfortunately, this good initial response decreases as treatment continues with conventional therapy, thus nullifying the benefits of the induction phase.