Faculty Bibliography

To assess the efficacy of therapy with the antiviral agent interferon in chronic hepatitis C (non-A, non-B hepatitis), we randomly assigned 166 chronic hepatitis C patients to treatment with either 3 million or 1 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after 6 months of interferon therapy was 46% in patients treated with 3 million units of interferon (p less than 0.001) and 28% in those treated with 1 million units (p less than 0.02), but only 8% in untreated patients. Serum alanine aminotransferase levels became completely normal in 22 of the 26 patients (85%) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56%) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histological improvement because of the regression of lobular and periportal inflammation. Relapse within 6 months after the completion of treatment occurred in 51% of the patients treated with 3 million units of interferon and 44% of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.

Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P less than 0.001) and 28 percent in those treated with 1 million units (P less than 0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.

Three patients with the acquired immunodeficiency syndrome had biliary obstruction resulting from benign strictures of the biliary tract. Stenosis of the distal common bile duct with differing degrees of irregularity of the smaller intrahepatic and extrahepatic ducts was seen in association with either cryptosporidial or cytomegaloviral infection of the biliary tree. We review cytomegaloviral and cryptosporidial infections of the biliary system, as well as possible relationships with idiopathic primary sclerosing cholangitis. Stenotic biliary tract disease appears to be yet another complication of the acquired immunodeficiency syndrome.

We report gastric or duodenal fistulas in 6 patients with Crohn's colitis or ileocolitis. Two patients had duodenocolic fistulas, 1 had a duodenoileal fistula, 2 had gastrocolic fistulas, and 1 had gastric and duodenal fistulas from an ileocolic anastomosis. In each case the fistula originated from the lower bowel segment, and no patient in this series had primary gastroduodenal Crohn's disease. These cases illustrate the range of manifestations of fistulas to the stomach and duodenum in Crohn's disease, and emphasize that the predominant symptoms determining surgical intervention usually arise from the diseased ileum and colon, rather than from the fistula. Our experience demonstrates the simplicity and safety of excision of the fistula with primary closure of the stomach or duodenum when the stomach and duodenum are otherwise normal by endoscopic examination.

We tested sera collected between 1976 and 1984 from 362 persons in a variety of epidemiologic categories with acute and chronic hepatitis B and from 76 hemophiliacs and drug addicts with hepatitis B antibodies for hepatitis D markers. Hepatitis D markers were common in hemophiliacs, drug addicts, Afghanistanis, prisoners and hemodialysis patients; rare in persons from other hepatitis-B endemic areas, persons with sporadic hepatitis B and homosexual men; and absent in health-care workers and institutionalized mentally retarded persons. No change was observed in the frequency of this infection during the 9 years of this study. We found hepatitis D markers in 5% of patients with acute hepatitis B, 1 of 3 with fulminant hepatitis and in 4 (1 in a homosexual male) of 12 episodes of acute hepatitis in hepatitis B carriers. Hepatitis D markers were more frequent in chronic liver disease (18%) than in asymptomatic hepatitis B carriage (2%), but there was no association between severity of chronic hepatitis and hepatitis D. These findings indicate that, to date, health-care workers and institutionalized mentally retarded persons have been spared from infection with this agent but suggest that homosexual males may not continue to be spared. Even in an area nonendemic for hepatitis D, this agent contributed to 20 to 30% of chronic hepatitis B and acute hepatitis superimposed on chronic hepatitis B infection.

To evaluate the immunogenicity of hepatitis B vaccine in renal transplant recipients, we administered three 40-microgram doses of vaccine to 17 patients who had previously undergone transplantation and were on immunosuppressive therapy. Life-table analysis revealed a cumulative antibody response rate of only 17.6% at 12 months, and the three responders had low titers of antibody to hepatitis B surface antigen. There were no serious adverse effects and no episodes of graft rejection in responders or nonresponders. In addition, the ratio of helper/inducer (T4) to suppressor/cytotoxic (T8) T cells in vaccinees bore no relationship to the immunogenicity of the vaccine. These data indicate that hepatitis B vaccine is weakly immunogenic in renal transplant recipients and illustrate the need for vaccination prior to transplantation for maximal protection against hepatitis B virus infection.

We report a patient with Wilson's disease whose case is unusual in two respects. First, the patient was 58 years of age when the diagnosis was made based on urinary, serum, and hepatic copper studies, as well as liver histological investigation. Second, despite the patient's neurological impairment, Kayser-Fleischer rings had not developed. We conclude that in patients with chronic, degenerative neurological disease, particularly when associated with hepatic dysfunction, the diagnosis of Wilson's disease should be considered regardless of age at onset or the absence of Kayser-Fleischer rings on slit lamp examination.

Three patients with a relapsing course of serologically confirmed viral hepatitis type A are presented. In addition, one patient had aminotransferase elevations for over 6 mo. In all three, hepatitis ultimately resolved. A relapsing or protracted course does not appear to alter the benign prognosis of hepatitis A.

Purified from the plasma of hepatitis B carriers, hepatitis B surface antigen particles have been used in a vaccine to prevent hepatitis B. This plasma-derived vaccine is immunogenic, protective, and has an excellent safety record. Indications and strategies for preexposure and postexposure prophylaxis are reviewed. In addition, novel approaches to hepatitis B vaccine development are being pursued and will provide the basis for the next generation of vaccines. Early progress has also been made toward a hepatitis A vaccine, but clinical availability is not imminent.