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About 350 million people worldwide have chronic hepatitis B virus (HBV) infection. Up to 40% of persons infected with the virus may go on to have complications related to cirrhosis or hepatocellular carcinoma. Antiviral therapy can suppress viral replication and halt the progression of liver disease in persons with chronic infection. In this article, the authors explore the modes of HBV transmission, describe the characteristics of chronic infection, and review the drugs available to treat it.

OBJECTIVE: Hepatitis C virus (HCV) is prevalent in patients with end stage renal disease who are on dialysis. Liver disease from HCV is a cause of substantial morbidity and mortality after kidney transplantation in infected recipients. Effective treatment of chronic HCV is needed in this group of patients. We aimed to determine from the literature the efficacy and safety of interferon monotherapy in dialysis patients with chronic HCV. METHODS: We reviewed the literature from 1986 to 2001 on the efficacy of interferon monotherapy in patients with HCV and end stage renal disease who were on dialysis. The outcomes measured were sustained viral response (SVR) and drop-out rate. RESULTS: We reviewed 17 studies, of which 11 studies with a total of 213 patients met criteria for our analysis. Eight studies evaluated 3 million units (MU) three times/wk (t.i.w.), and three studies evaluated higher doses. The pooled SVR for 3 MU was 33% (95% CI = 21-51%). The pooled SVR for genotype 1 patients was 26% (95% CI = 15-37%). Of 152 patients in eight studies treated with 3 MU t.i.w. of interferon monotherapy, 45 patients (29.6%) discontinued therapy because of side effects. CONCLUSIONS: Our analysis suggests that interferon monotherapy is more effective in patients on dialysis than in patients with normal renal function. Interferon monotherapy is associated with more adverse events in dialysis patients. The optimal dose and duration of interferon monotherapy and selection criteria of dialysis patients need to be studied further in clinical trials.

Chronic infection with hepatitis C virus (HCV) is associated with disturbances of B lymphocyte activation and function: autoantibody production, mixed cryoglobulinemia, and B cell lymphomas. It has been proposed that these abnormalities reflect chronic antigenic stimulation or aberrant signaling through the B cell coreceptor, the latter mediated by binding of the HCV E2 glycoprotein to CD81. To test this hypothesis, we measured expression of activation and differentiation markers on peripheral blood B cells from patients with chronic HCV infection. Thirty-six HCV patients with and without mixed cryoglobulinemia were compared with 18 healthy control volunteers and 17 sustained virologic responders who had cleared HCV infection. Ten of the 36 HCV patient samples showed increased B cell frequencies; B cell frequency was higher in patients with more severe hepatic fibrosis. However, these samples lacked evidence of Ag-driven activation or proliferation. The expanded cells were low in the activation markers CD25, CD69, CD71, CD80, and CD86. Proliferation of circulating B cells was unchanged in HCV patients. These cells did not express the differentiation marker CD27, suggesting that they were not enriched in memory B cells. Furthermore, the expanded B cells expressed both IgD and IgM, suggesting that they were antigenically naive. Together, these results indicate that B cell expansion in the peripheral blood of HCV patients is not associated with Ag-mediated activation and differentiation. Instead, factors other than antigenic stimulation may promote the accumulation of peripheral blood B cells with a naive phenotype in a subset of HCV patients

OBJECTIVE: The aim of this study was to analyze the clinical presentation and outcomes of significant pulmonary toxicity associated with interferon and ribavirin. METHODS: We conducted a retrospective review of patients enrolled in four clinical trials at three sites, two academic medical centers and one community practice, and reviewed the literature. RESULTS: Four patients, while on therapy with interferon a and ribavirin for chronic hepatitis C, developed significant pulmonary signs and symptoms. Further workup, which included lung biopsy in three, revealed bronchiolitis obliterans organizing pneumonia in two, and interstitial pneumonitis in two other cases. There were no other predisposing factors for lung disease identified. Resolution of symptoms occurred in all patients upon discontinuation of interferon and ribavirin, with or without corticosteroid therapy. One of the patients developed pulmonary complications while on a clinical trial of pegylated interferon and represents the first reported case associated with the use of long-acting interferon in chronic hepatitis C infection. CONCLUSIONS: A spectrum of significant pulmonary toxicity, including bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis, can occur with interferon or pegylated interferon in combination with ribavirin. Though pulmonary toxicity of interferon is well known, these cases represent the first cases reported in the literature with combination therapy. It is likely that pulmonary toxicity may not be investigated in patients on combination therapy because of the frequent pulmonary symptoms with ribavirin. Though usually reversible, at least one case has required long-term steroids with inadequate resolution. Though pulmonary toxicity is rare, symptoms which are more than mild or progressive in nature should likely be investigated

BACKGROUND: Premature stent clogging is the major limitation with plastic stents used in the treatment of malignant biliary structures. A pilot study suggested improved duration of patency of the Tannenbaum stent compared with polyethylene stents. The aim of this prospective, multicenter randomized trial was to compare the Tannenbaum Teflon stent with a conventional polyethylene endoprosthesis (Cotton-Leung biliary stent set) for the treatment of malignant biliary strictures. METHODS: Patients over age 18 years with symptoms caused by nonhilar malignant biliary strictures were enrolled. Patients were randomized to receive a 10F Tannenbaum or polyethylene stent after a guidewire was passed beyond the stricture. One hundred six patients (mean age 72 years and 71 years, respectively) were enrolled (54 Tannenbaum, mean age 72 years; 52 polyethylene, mean age 71 years). RESULTS: Tannenbaum and polyethylene stent placement was successful in, respectively, 100% and 96% of procedures without complications. The mean (SD) 90-day stent patency of the Tannenbaum stent was 67% (7%) compared with 73% (7%) for the polyethylene stents. CONCLUSIONS: The present study demonstrated no difference in ease of implantation or stent patency between Tannenbaum and polyethylene stents.

Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting