Long-term liver histology improvement in patients with chronic hepatitis C and sustained response to interferon.

A retrospective multicentre survey was conducted to evaluate, in patients with chronic hepatitis C, the long-term liver histological changes induced by interferon (IFN). A total of 112 patients (mean age 46.4 years) were studied. All patients had received a 6-12-month IFN-alpha course (6-18 MU/week) and had successively undergone clinical, biochemical and virological follow-up for at least 36 months (range: 36-76). In each patient, two liver biopsies had been performed: 1-6 months before treatment and, 12-76 months after its completion. In 87 patients with biochemical and virological sustained response persisting for 12 months after therapy, post-treatment liver necroinflammation and fibrosis mean(+/-SD) scores (Knodell index) were significantly lower than pretreatment scores (2.9 +/- 2.2 vs 6.8 +/- 2.9 and 0.8 +/- 1.0 vs 1.2 +/- 1.1, respectively; P < 0.01). In 25 patients who relapsed within 1 year, necroinflammation and fibrosis post-treatment mean scores were similar to pretreatment scores (7.4 +/- 3.2 vs 6.9 +/- 3.1 and 1.8 +/- 1.3 vs 1.6 +/- 1.2, respectively; P > 0.05). On an individual basis, necroinflammation decreased in 87% of sustained responders but only in 36% of relapsers (P < 0.001), whereas fibrosis decreased in 44% of sustained responders but only in 14% of relapsers (P < 0.001). In sustained responders with biopsies performed 12-23 months (n=34), 24-35 months (n=26) or more than 36 months (n=27) after treatment, a progressive decrease of mean necroinflammatory score was observed (-2.6 +/- 2.1, -4.1 +/- 3.4 and -5.2 +/- 3.7 points, respectively; P < 0.01). A similar pattern was observed in fibrosis score (-0.3 +/- 0.6, -0.3 +/- 0.7 and -0.7 +/- 0.9 points, respectively; P < 0.05). Hence, among chronic hepatitis C patients treated with IFN, those with a 12-month sustained response, unlike those who relapse, have a long-term progressive reduction and, in some cases, a complete regression of liver histological damage.

Doppler sonography measurement of portal blood flow velocity after glucagon injection in patients with chronic HCV infection.

Doppler sonography measurement of portal flow velocity (PFV) after glucagon injection was performed in 45 patients with chronic hepatitis C virus (HCV) infection. Patients were divided into three groups: group 1 = no or mild liver fibrosis; group 2 = moderate to severe liver fibrosis, and group 3 = liver cirrhosis. All patients were examined using a Doppler ultrasound (US) multipurpose equipment and a convex 3.5-MHz probe, 10 min before (baseline), as well as 5 and 10 min after, IV administration of 1 mg of glucagon chloride. No significant differences were found in mean baseline PFV among group 1 (19.4 +/- 2.4 cm/s), group 2 (20.1 +/- 3.6 cm/s) and group 3 (17.5 +/- 3.7 cm/s). Five minutes after glucagon injection, all three groups showed significantly increased values of mean PFV (25.6 +/- 4.8, 23.7 +/- 4.0 and 19.5 +/- 5.0 cm/s, respectively; p < 0.05 vs. baseline). The mean increase of PFV above baseline was significantly higher in group 1 (7.9 +/- 3.7 cm/s) than in group 2 (4.5 +/- 3.9 cm/s) (p < 0.05) or in group 3 (2.7 +/- 2.3 cm/s) (p < 0.05). A significant inverse correlation was found between individual values of fibrosis score and of individual increase of PFV. In patients with chronic HCV infection, Doppler sonography measurement of PFV after glucagon injection could be useful in assessing the severity of liver histological damage.

Leukocyte and platelet lowering by some interferon types during viral hepatitis treatment.

BACKGROUND/AIMS: The hematologic toxicity (leukothrombocytopenia) of interferon therapy is well known and frequently observed; it may vary, however, according to the type of interferon administered. METHODOLOGY: We retrospectively assessed 158 patients with chronic viral hepatitis treated for 6-12 months with alpha (recombinant, lymphoblastoid or leukocyte) or beta interferon to monitor leukothrombocytopenia. RESULTS: During treatment, a significant decrease in leukocyte and platelet counts was detected in 48% and 43% of patients, respectively. The maximum decrease (31% and 26% of pre-treatment values; p<0.01) occurred after 4.9 and 4.2 months of treatment. No patient showed clinical symptoms of leukopenia or thrombocytopenia. Beta-interferon yielded the smallest decreases in leukocyte and platelet counts (-21% and -16% of pre-treatment values, respectively). Among alpha interferons, the lymphoblastoid (9 MU/week) produced the largest decrease both in leukocyte (38%; p<0.05 vs any other type) and in platelet (32%) number. The same dose of leukocyte interferon had the smallest effect (leukocytes: -27%; platelets: -2%), while recombinant interferon showed intermediate toxicity (-32% and -26% respectively). CONCLUSIONS: From this retrospective study, the hematologic toxicity of alpha and alpha interferons usually emerges as mild. However, leukopenia and thrombocytopenia may be induced more frequently by some of these interferon types.

Comparison of treatment with two different doses of leukocyte interferon alpha in patients with chronic hepatitis C.

BACKGROUND/AIMS: This study was carried in order to investigate whether human leukocyte interferon-alpha administered for 12 months at two different dosages, improves long-term responses in chronic hepatitis C and to see whether pre-treatment gamma-glutamyl transpeptidase values help to predict the clinical response to Interferon. METHODOLOGY: Forty-five patients were treated for 12 months with natural Interferon-alpha: 3 MU (group A: 31 cases); 6 MU (group B: 14 cases). Biochemical and virological responses were monitored during treatment and follow-up. RESULTS: Alanine aminotransferase was normalized in 58.1% (Group A) and 54.5% (Group B) of patients by the end of the treatment. Due to side effects 3 patients had to discontinue treatment. During follow-up, remission was maintained in 30.8% and 45.4% of patients respectively (p = 0.046). After 12 months of therapy, respectively 46.7% and 45.4% of patients with complete biochemical response, cleared virus from serum, as did, among long-term responders, 3/8 and 3/4 evaluated patients. Independently of dosage, a complete response was found more often in patients with normal pre-treatment gamma-glutamyl transpeptidase than in those with pre-treatment abnormal values. CONCLUSIONS: High dosage of IFN alpha was associated with a significantly greater rate of sustained biochemical response and with a better chance of viremia becoming negative. Pre-treatment gamma-glutamyl transpeptidase was able to predict the outcome of the treatment.