Faculty Bibliography

In a randomized, controlled trial that demonstrated the efficacy of interferon alfa-2b 3 million units three times a week for 24 weeks in controlling chronic hepatitic C (non-A, non-B), the Sickness Impact Profile (SIP) was used to evaluate the impact of disease and treatment on health-related quality of life (HRQOL). The SIP was self-administered by 160 patients before treatment, at the end of treatment, and at the study endpoint. Before treatment, patients with chronic hepatitis C scored significantly (P < 0.05) higher (worse) than an historical control group of the general population in mean total SIP score and in all categories except eating. The highest degree of impairment was observed in the work, sleep and rest, and recreation and pastimes categories. After treatment, patients who received interferon alfa-2b had significant (P < or = 0.05) improvement in work, sleep and rest, and recreation and pastimes scores. Numerical improvement was observed in total score, physical and psychosocial dimension scores, and most individual category scores. Mean SIP scores were unchanged or slightly worsened in untreated control patients. In responders (patients with improvement in serum alanine aminotransferase levels), the largest improvement was seen in work scores. The SIP appears to be a reliable and valid instrument for describing the impact of chronic hepatitis C on HRQOL but lacks disease-specificity and the ability to reflect clinically relevant changes. Thus the SIP is not the best instrument to evaluate the HRQOL effects of treatment with interferon alfa-2b in patients with chronic hepatitis C.

BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.

Cholelithiasis and its complications, along with malignancy, account for the majority of biliary and pancreatic diseases in the elderly and increase in frequency with advancing age. The presentation is often subtle and requires a high index of suspicion on the part of the clinician. Surgical management of pancreaticobiliary disease usually is associated with an increased morbidity and mortality relative to younger patients, although in some cases surgery still remains the best treatment modality. A major advance has been the development of nonsurgical therapeutic techniques, such as endoscopic sphincterotomy and biliary endoprostheses.

Malignant obstruction of the pancreaticobiliary system is a frequent indication for ERCP. Twenty-five patients with abnormalities suggestive of malignancy were encountered during ERCP at our institution and brush cytology was obtained. Positive cytology specimens were collected in 12 of 20 (60%) cases of malignancy causing biliary obstruction. Using a recently developed cytology brush for the biliary tree, detection of malignancy in strictures of the bile duct had a sensitivity of 50% and a specificity of 100%. Both cases of cholangiocarcinoma were diagnosed with cytology, as were 5 of 10 cases of pancreatic cancer. It is concluded that brush cytology is a diagnostically reliable, highly specific technique for malignant lesions encountered at ERCP. In experienced hands, a positive cytologic result may obviate the need for additional invasive diagnostic studies.

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.