Highlights of the 2012 American Association for the Study of Liver Diseases meeting.

The American Association for the Study of Liver Diseases (AASLD) held its annual meeting from November 9, 2012, through November 13, 2012, in Boston, Massachusetts. Hepatitis C virus (HCV) was prominently featured in the meeting, reflecting the rapid pace at which new developments in the field of HCV treatment are being introduced. HCV was the topic of an estimated 451 of the 2051 submitted abstracts (22%), with 148 abstracts (7.2%) focused on investigational drugs; it was also the topic of 1 presidential plenary session (top oral abstracts), 1 symposium, 10 of 37 parallel sessions (oral abstracts), and 1 debriefing session at the close of the meeting. This article will summarize some of the major findings presented at the meeting.

Development of fatal acute liver failure in HIV-HBV coinfected patients.

Coinfection with hepatitis B virus (HBV) is not uncommon in human immunodeficiency virus (HIV)-infected individuals and patients with HIV-HBV coinfection are at high risk for progression of liver disease. Current guidelines regarding the treatment of HIV infection recommend that patients who are coinfected with HIV and HBV receive highly active antiretroviral therapy (HAART) with activity against hepatitis B. While HIV-HBV coinfected patients often experience liver enzyme elevations after starting antiretroviral therapy, acute liver failure (ALF) is rare and typically occurs with older antiretroviral agents with known potential for hepatotoxicity. We describe two cases of fatal ALF in the setting of HIV-HBV coinfection after initiation of HAART. These cases occurred despite treatment with antiretrovirals that have activity against HBV and highlight the challenges in distinguishing drug hepatotoxicity and HBV immune reconstitution inflammatory syndrome. HIV-HBV coinfected patients should be monitored closely when initiating HAART, even when treatment includes agents that have activity against HBV.

Acute hepatitis C and HIV coinfection.

Hepatitis C is a common infection worldwide, but acute infection is often asymptomatic and difficult to diagnose. People coinfected with HIV and hepatitis C might progress to chronic liver disease more quickly. We present a case of a man infected with HIV with sexually acquired acute hepatitis C and discuss the immunology, natural history, and epidemiology of acute hepatitis C and coinfection with HIV. Several recent reports have documented acute hepatitis C among men who have sex with men who engage in high risk sexual practices and often have concomitant genital ulcer disease. We review treatment options for the medical management of acute hepatitis C and coinfection with HIV.

Safety and efficacy of telbivudine for the treatment of chronic hepatitis B.

Telbivudine was recently approved for the treatment of chronic hepatitis B. Phase III studies indicated its antiviral potency with 6- to 6.5-log copies/mL reductions in hepatitis B DNA levels at year 1, comparable to other potent agents such as entecavir or tenofovir. Genotypic resistance rates, however, reached 25% at year 2 in hepatitis B e-antigen positive subjects and 11% in hepatitis B e-antigen negative subjects, preventing it from becoming a preferred first-line drug for hepatitis B. Furthermore, its signature resistance mutation (a change from methionine to isoleucine at position 204 in the reverse transcriptase domain of the hepatitis B polymerase) also confers cross-resistance to entecavir, lamivudine, and emtricitabine. Telbivudine is well tolerated, with elevations in creatine phosphokinase being the most common abnormality observed in clinical trials. Most often, elevations were asymptomatic. Future research in hepatitis B will focus on the best ways to use existing therapies, including telbivudine, sequentially or in combination in order to maximize viral suppression and minimize the development of antiviral resistance.

Impaired hepatitis C virus (HCV)-specific effector CD8+ T cells undergo massive apoptosis in the peripheral blood during acute HCV infection and in the liver during the chronic phase of infection.

A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8(+) T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8(+) T cells during the acute and chronic stages of infection. Although HCV-specific CD8(+) T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8(+) T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8(+) T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the "death phase" of HCV-specific CD8(+) T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections.

Outcomes of patients with hepatitis B who developed antiviral resistance while on the liver transplant waiting list.

BACKGROUND & AIMS: Lamivudine has been shown to improve liver disease and survival of hepatitis B virus patients on the orthotopic liver transplantation (OLT) waiting list, but liver failure might worsen in patients with drug resistance. Use of antiviral salvage therapy might decrease this risk. METHODS: We analyzed data from patients enrolled in the NIH HBV OLT cohort to study the effects of pretransplant antiviral therapy on transplant-free survival and survival without transplant. We also compared the clinical outcomes of those who did or did not develop antiviral failure (virologic breakthrough or genotypic resistance) while awaiting transplant. RESULTS: One hundred twenty-two eligible patients received antiviral therapy before OLT and were followed for a median of 40.5 months (range, 0.4-123.0 months) after initiation of antiviral therapy. Forty-four (36.1%) patients developed antiviral failure; all had lamivudine monotherapy as initial treatment. Forty-two patients started salvage therapy a median of 5 months after lamivudine failure; the median Model for End-Stage Liver Disease (MELD) score was 12. Twenty-one (50%) patients had a full response to salvage therapy. Eleven (26.2%) patients had a suboptimal virologic response but remained clinically compensated. Antiviral failure was not a significant predictor of transplant or death (P = .09) or death without transplant (P = .39). Multivariate predictors of transplant or death were high MELD score, hepatocellular carcinoma, and low albumin. High MELD score and low albumin were predictors of death without transplant. CONCLUSIONS: Antiviral failure in patients with HBV on the OLT waiting list did not impair clinical outcome if recognized early and if salvage therapy is promptly initiated.

Subdural empyema and other suppurative complications of paranasal sinusitis.

Suppurative intracranial infection, including meningitis, intracranial abscess, subdural empyema, epidural abscess, cavernous sinus thrombosis, and thrombosis of other dural sinuses, are uncommon sequelae of paranasal sinusitis. A high index of suspicion is necessary to identify these serious complications. We present a patient with subdural empyema in whom the diagnosis was delayed, followed by a discussion of suppurative complications of sinusitis. The case shows the rapid progression of subdural empyema, which represents a true neurosurgical emergency requiring prompt diagnosis and management.

Antiviral options for the treatment of chronic hepatitis B.

Hepatitis B virus (HBV) is an important cause of end-stage liver disease and hepatocellular carcinoma. Effective treatment can delay or prevent these outcomes. The decision to treat is based on the activity of liver disease and HBV replication status, and the likelihood of a long-term benefit. Approved therapies include standard and pegylated interferon-alfa and nucleoside analogues: lamivudine, adefovir and entecavir. Current therapies do not eradicate HBV so long-term treatment is usually required. Development of drug resistance is a major concern with long-term treatment. Even with successful therapy, patients remain at risk for reactivation of viral replication and require lifelong monitoring.