C. Masci

A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C

BACKGROUND/AIMS In chronic hepatitis C, interferon alfa (IFN-alpha) therapy fails to achieve a sustained response in approximately 75% of patients. Similarly, ribavirin induces only a transient response. The aim of this study was to evaluate whether ribavirin and IFN-alpha in combination could be effective in IFN-alpha-resistant chronic hepatitis C. METHODS Twenty patients with chronic hepatitis C resistant to a previous course of IFN-alpha were randomly assigned to receive either ribavirin combined with IFN-alpha or IFN-alpha alone for 6 months. RESULTS Serum alanine aminotransferase levels decreased significantly during therapy in both treatment groups, but after therapy, the levels remained significantly decreased only in the combination therapy group. Nine months after treatment, sustained normalization of aminotransferase levels, associated with sustained loss of serum hepatitis C virus RNA, was observed in 40% of the patients in the combination therapy group but in none of the patients treated with IFN-alpha alone (P < 0.05). The sustained response was accompanied by reduced hepatic necroinflammatory activity on biopsy. CONCLUSIONS These findings suggest that ribavirin plus IFN-alpha combination therapy is able to induce a sustained biochemical and virological response in a significant proportion of patients with IFN-alpha-resistant chronic hepatitis C.

Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia

Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients.

Persistent hepatitis C viraemia without liver disease

In viral infections persistence of the virus is not always associated with virus-induced disease. To find out if active hepatitis C virus (HCV) infection can persist without liver disease we selected four symptom-free individuals with antibodies to HCV but normal aminotransferase levels. They were followed up for 3 years by monthly serology and a liver biopsy was done. At presentation, all four had both antibodies to HCV and circulating HCV RNA. During follow-up their sera remained persistently positive for all HCV antibodies and RNA yet aminotransferase levels did not increase and liver biopsy was normal. These findings indicate that persistent hepatitis C viraemia is not invariably associated with liver damage.

Serological and histological aspects of hepatitis C virus infection in alcoholic patients

The recent cloning of the genome of hepatitis C virus (HCV) has allowed the detection of antibodies to HCV (anti-HCV) in human serum. The presence of serum antibodies to HCV often indicates active infection with HCV. We have assessed the serological and histological features in a group of alcoholic patients with chronic liver disease and have evaluated the possible etiologic role of HCV infection in the development of liver damage. Serum samples and liver biopsy specimens were obtained from 41 consecutive patients, all having a definite history of alcohol abuse and evidence of chronic hypertransaminasemia. Fifteen patients (37%) were positive for anti-HCV by ELISA, and 13 (86.6%) of them were also positive by RIBA. Eleven of these patients had histologic features of chronic active hepatitis (CAH), a lesion which is not known to be induced by excessive alcohol intake. No other possible causes of CAH were found, and CAH was not present in any of the anti-HCV negative patients. In patients with CAH, mean AST to ALT ratio was less than 1 (0.6), a finding which is characteristic of viral rather than alcoholic chronic liver disease. In conclusion, our study suggests that sporadic hepatitis C virus infection plays an etiologic role in the development of chronic active liver disease in a subgroup of alcoholic patients.

HCV infection and chronic active hepatitis in alcoholics.

Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found.

Detection of serum IgM antibody to hepatitis C virus in chronic non-A, non-B hepatitis

Detection of serum IgM antibody to a specific viral antigen is a marker of active virus infection and virus-induced disease. We assessed a procedure for a specific solid phase enzyme immunoassay able to capture and measure circulating IgM antibody to HCV. Serum samples were taken from 10 normal subjects, 60 consecutive patients with clinical ly and histologically proven chronic non-A, non-B hepatitis (NANBH) and 5 prospectively followed tran sfusion recipients with chronic NANBH. Each serum sample was tested for IgG anti-HCV (Drtho HCV Elisa) and IgM anti-HCV. Results: All normal subjects were IgG and IgM anti-HCV -ve. The 5 patients with chronic post-transfusion hepatitis seroconverted to both IgM and IgG anti-HCV. and antibodies persisted in serum during the chronic phase of the disease. Serum IgG anti-HCV was found in 44 out of 60 patien ts with chronic sporadic NANBH (73%). None of the 16 IgG anti-HCV -ve patients was positive for IgM anti-HCV instead of 21 out of 44 IgG anti-HCV +ve patients (48%) who tested positive also for IgM anti-HCV. @elusions: IgM anti-HCV was found only in the minority or patients with chronic NAN&