Background and Aims: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV. Approach and Results: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35–364); and bilirubin 0.5 mg/dL (0.2–1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation. Conclusions: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.

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Pretreatment of organ allografts to reduce graft immunogenicity is an attractive and potentially clinically applicable concept. We have studied the effect of perfusing rat pancreases with anti-class II monoclonal antibody (MoAb), to remove class II- positive accessory cells from the intact organ, on prolongation of allograft survival after transplantation. The capacity of pancreatic islets obtained from these perfused organs to stimulate proliferation of allogeneic T-lymphocytes was studied in a mixed islet-lymphocyte culture (MILC). There was a significant prolongation in pancreas-allograft survival when intact pancreases were transplanted after a 3-h normothermic perfusion with MoAb reactive with class II antigens (16.2 +/- 3.6 days, n = 19) compared with control animals (11.0 +/- 1.4 days, n = 24). In vitro treatment of islets with MoAb and complement (CI) inhibited their stimulatory capacity in the MILC, as measured by [3H]thymidine uptake. Similarly, the stimulatory capacity of islets removed from perfused pancreases was also abrogated when MoAb was included in the perfusate. Although reduction in graft immunogenicity, by increasing allograft survival, was achieved by a 3-h pretreatment regimen, it was not sufficient to inhibit rejection altogether in our transplant model.

Objectives:We sought to evaluate the prevalence, predictors and significance of autoantibody expression in patients with chronic hepatitis C (CHC) with or without HIV co-infection. Methods:Retrospective review of laboratory and histologic data for all patients with CHC who had a liver biopsy available. HIV status was documented in all patients. Results analyzed in SPSS10, Chicago, IL, a p value o0.05 was considered significant. Results: 170 patients with hepatitis C viremia, including 107 (63%) HIV co-infection, who had testing for anti-nuclear antibody (ANA) or antismooth muscle antibody (ASMA) and anti-mitochondrial antibody (AMA) were included in the study. Overall, 63% (74/117) of patients were ASMA seropositive and 6% (9/153) were positive for ANA. All 117 patients tested for AMA were negative. HIV co-infected patients were significantly more likely to be ASMA positive 71% (53/75) compared to those with hepatitis C alone (50%) [P 5 0.026]. There were no significant differences in age, gender, race, risk group, alanine aminotransferase (ALT) levels or grade of inflammation on histology between autoantibody positive and negative patients. ASMA positive patients had significantly higher globulin levels (P 5 0.036) and a trend towards more bridging fibrosis or cirrhosis. Patients with autoantibody expression rarely had histologic features of AIH. Conclusion:We found a high rate of ASMA seropositivity in our cohort of patients with chronic hepatitis C, and HIV co-infection was associated with significantly higher rates of ASMA expression. Autoantibody expression was not associated with demographic or clinical characteristics and does not necessarily preclude antiviral therapy.

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