Understudied populations with hepatitis C

Abstract

Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR).Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus ( H epatitis C is an important cause of acute and chronic liver disease worldwide and the most common indication for liver transplantation in adults in the United States. Since the discovery of the hepatitis C virus (HCV) in 1989 and its linkage to non-A, non-B hepatitis, there have been major advances in knowledge of the incidence and prevalence of this infection, its clinical manifestations, natural history, molecular virology, histopathology, and treatment. At present, the management of patients with hepatitis C focuses largely on combination antiviral treatment using a 24-or 48-week course of peginterferon and ribavirin. Two large trials evaluating the safety and efficacy of this combination therapy have demonstrated sustained virological responses (SVR) in slightly more than 50% of patients. 1,2 It is important to stress, however, that response rates of 50% in randomized, controlled trials of therapy do not guarantee that 50% of all patients with chronic hepatitis C can be or will be successfully treated. Patients enrolled in the registration trials of combination therapy were highly selected and not fully representative of the broader population of patients with chronic HCV infection. The strict inclusion and exclusion criteria used in registration trials often exclude populations that have high rates of hepatitis C. Furthermore, chronic hepatitis C is common in populations that are not reached by clinical trials of new and investigational therapies. Because patients enrolled in registration trials of new antiviral treatments are a selected group, the applicability of results of these trials to the general population is problematic.

Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis

“…Shortcomings of current therapy include the protracted and complicated nature of treatment and unpleasant side effects. In addition, SVR rates are only 50-60% in published clinical trials and are appreciably lower in community practice [44,45]. Therapy is usually recommended only for patients with evidence of fibrosis or substantial necroinflammatory disease on liver biopsy [5,6].…”

Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus

“…When cyclosporine was administered alone, blood samples were collected for cyclosporine analysis on day 1, period 1 (sampling timepoints: predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3,4,6,8,12,16,24, and 48 hours postdose). When cyclosporine was coadministered with telaprevir, blood samples were collected for cyclosporine analysis on days 1 and 8, period 2 (sampling timepoints: predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3,4,6,8,12,16,24,48,72, and 96 hours postdose). For telaprevir concentration analysis, blood samples were drawn on day 1 and day 8, period 2 (sampling timepoints: predose, 0.5, 1, 2, 2.5, 3, 4, 6, and 8 hours post-morning dose).…”

“…When tacrolimus was administered alone, blood samples were collected for tacrolimus analysis on day 1, period 1 (sampling timepoints: predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3,4,6,8,12,16,24,48,72,96, and 120 hours postdose). When tacrolimus was coadministered with telaprevir, blood samples were collected for tacrolimus analysis on day 8, period 2 (sampling timepoints: predose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours postdose).…”

“…[11][12][13][14][15] Patients who are not eligible for standard treatment often require liver transplant due to accompanying comorbid conditions. 16 Recurrence of HCV infection occurs in 100% of liver transplantations if not eradicated prior to transplantation. 17 Cyclosporine and tacrolimus are immunosuppressants with narrow therapeutic ranges used in the postoperative phase of liver or kidney transplants to prevent allograft rejection.…”

Safety and efficacy of pegylated interferon -2a and ribavirin for the treatment of hepatitis C in patients with thalassemia

“…2 Furthermore, iron overload and HCV infection have been shown to be independent risk factors for progression of liver fibrosis. 3 Patients with hemoglobinopathies have traditionally been excluded from large studies of therapy of HCV, 4 particularly studies that include ribavirin because of the associated hemolysis 5 leading to an increase in transfusion requirement, iron accumulation and risk of iron-related toxicities. Furthermore, increased iron stores have been associated with poor response to interferon-ribavirin treatment.…”