Faculty Bibliography

SUMMARY: Coinfection with HIV and hepatitis C virus (HCV)-specific immune responses, increases hepatic inflammation, accelerates hepatic fibrosis, and is associated with deceased treatment responses. We quantified intrahepatic lymphocyte and hepatocyte phenotypes in HCV-infected patients with (n = 38) and without (n = 41) HIV infection. A single pathologist counted positive cells in 5 portal and 5 lobular areas. Coinfected patients had 6.81 +/- 1.9 fewer CD4 cells per portal field (10.58 +/- 1.12 vs. 4.97 +/- 1.09 cells/high-power field [HPF]; P < 0.001) and 0.48 +/- 0.15 more apoptotic lymphocytes per lobular field (0.16 +/- 0.06 vs. 0.64 +/- 0.15 cell/HPF; P = 0.002) than monoinfected patients. The number of portal CD4 cells was not associated with the peripheral CD4 cell number. Portal and lobular CD8 cells did not differ between the 2 groups. Portal proliferative hepatocytes were increased in coinfected patients with HIV RNA levels of >400 copies/mL (1.13 +/- 0.32 cells/HPF; P = 0.01) compared with those with undetectable HIV RNA (0.46 +/- 0.09 cell/HPF) and monoinfected patients (0.45 +/- 0.08 cell/HPF). In conclusion, HIV coinfection is associated with fewer portal CD4 cells and increased lobular lymphocyte apoptosis that may impact on the natural history of HCV infection

BACKGROUND AND AIMS: Chronic hepatitis B is an important public health problem worldwide and in the United States. A treatment algorithm for chronic hepatitis B virus (HBV) infection was developed by a panel of US hepatologists based on new developments in the understanding of the virology of HBV, availability of more sensitive molecular diagnostic testing, and advantages and disadvantages of currently approved therapies. METHODS: This algorithm is based on available evidence, but where data are lacking, the panel relied on clinical experience and consensus expert opinion. RESULTS: Serum HBV DNA can be detected at levels as low as 100-1000 copies/mL by using molecular assays and should be determined to establish a baseline level before treatment, monitor response to antiviral therapy, and survey for the development of drug resistance. The primary aim of antiviral therapy is durable suppression of serum HBV DNA to the lowest level possible. The threshold level of HBV DNA for determination of candidacy for therapy is >/=10(5) copies/mL for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. A lower serum HBV DNA threshold is appropriate for patients with HBeAg-negative chronic hepatitis B and those with decompensated cirrhosis, and the panel recommends thresholds of 10(4) copies/mL and 10(3) copies/mL, respectively. CONCLUSIONS: Interferon alfa-2b, lamivudine, and adefovir dipivoxil are all approved as initial therapy for chronic hepatitis B and have certain advantages and disadvantages. Issues for consideration include efficacy, safety, incidence of resistance, method of administration, and cost. Studies are under way to explore the safety and efficacy of combination therapy, which may prove to be more effective than monotherapy in suppressing viral replication and may decrease or delay the incidence of drug resistance

The aim of this study was to determine the efficacy of epoetin alfa in alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients with chronic hepatitis C virus (HCV) infection receiving combination RBV/interferon alfa (IFN) therapy.HCV-infected patients who had Hb levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy (n = 64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or to standard of care (SOC) for anemia management (RBV dose reduction or discontinuation, transfusions). Primary and secondary efficacy endpoints were changes in Hb level and RBV dosage, respectively, from baseline to week 16 of epoetin alfa therapy.Based on intent-to-treat analysis, the mean changes from baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl for SOC (p < 0.0001), and the mean changes in RBV dosage were -34 mg/day for epoetin alfa versus -146 mg/day (p = 0.060) for SOC. The mean Hb level at week 16 in the epoetin alfa group (13.8 g/dl) was significantly (p < 0.0001) higher than that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more patients in the epoetin alfa group did not have RBV dosage reductions (p < 0.011). At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at least 800 mg/day, compared with 54% of patients receiving SOC (p = 0.022). Epoetin alfa was well tolerated.In anemic HCV-infected patients treated with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on these results, epoetin alfa seems to be promising in the treatment of HCV treatment-related anemia. Further research is warranted to determine the potential impact on outcomes, including quality of life and sustained viral response rate

HAART has resulted in dramatic declines in morbidity and mortality among patients infected with HIV. Increased experience with HAART has led to the detection of drug related toxicities that may compromise adherence and necessitate discontinuation of treatment and alteration of otherwise effective regimens. This article considers the major long-term complications associated with nucleoside reverse transcriptase inhibitor (NRTI) use--hyperlactatemia and lactic acidosis/hepatic steatosis, other hepatotoxicities, pancreatitis, lipodystrophy, lipoatrophy, neuropathy, and hematologic toxicities. Mechanisms by which NRTIs may produce these effects are discussed, as are differential effects of agents in this class and management options