Carla S. Coffin

OBJECTIVES: Few population-based studies have evaluated pyogenic liver abscess (PLA) in North America. We assessed the incidence of PLA and evaluated predictors of mortality. METHODS: We used the Nationwide Inpatient Sample to identify all patients with discharges for PLA (ICD-9 572.0) between 1994 and 2005. Multivariable logistic regression analysis was performed to determine whether mortality was associated with patient and hospital characteristics including comorbidities, interventions, and bacterial cultures. We determined the annual incidence for PLA in the US population and assessed for temporal changes using generalized linear regression models. RESULTS: We identified 17,787 PLA discharges for an overall incidence of PLA of 3.6 (95% confidence interval (CI): 3.5-3.7) per 100,000 population. From 1994 to 2005, the annual average percent increase in incidence was 4.1% (95% CI: 3.4-4.8; P<0.0001). In-hospital mortality was 5.6% (95% CI: 5.3-6.0). Mortality was associated with older age (65-84 vs. 18-34: odds ratio (OR)=2.28 (1.48-3.51)); Medicaid (OR=1.74 (1.36-2.23)) and Medicare (OR=1.48 (1.18-1.85) vs. private insurance; and comorbidities such as cirrhosis (OR=2.48 (1.85-3.31)), chronic renal failure (OR=1.99 (1.28-3.09)), and cancer (OR=2.32 (1.97-2.73)). Patients who underwent percutaneous liver aspiration (OR=0.45 (0.39-0.52)) had lower mortality, whereas surgical drainage (OR=0.87 (0.68-1.10)) and endoscopic retrograde cholangiopancreatography (OR=0.73 (0.52-1.03)) were not associated with mortality. The most commonly recorded bacterial infections were Streptococcus species (29.5%) and Escherichia coli (18.1%). Patients with bacteremia or septicemia (OR=3.88 (3.36-4.48)) had an increased risk of death. CONCLUSIONS: The incidence of PLA is increasing and is associated with significant mortality that is attributable to several modifiable risk factors.

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.

Chronic hepatitis B virus (HBV) infection can lead to substantial morbidity and mortality. Although treatment is not considered curative, antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality. Effective vaccines to prevent hepatitis B are available. This report updates and expands CDC’s previously published Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection (MMWR Recomm Rep 2008;57[No. RR-8]) regarding screening for HBV infection in the United States. New recommendations include hepatitis B screening using three laboratory tests at least once during a lifetime for adults aged ≥18 years. The report also expands risk-based testing recommendations to include the following populations, activities, exposures, or conditions associated with increased risk for HBV infection: persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting; persons with a history of sexually transmitted infections or multiple sex partners; and persons with a history of hepatitis C virus infection. In addition, to provide increased access to testing, anyone who requests HBV testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.

BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and⁄or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions. AIMS: To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study. METHODS: Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks. RESULTS: Rituximab was well tolerated with no serious adverse events. By week 24, mean (± SD) aspartate aminotransferase (AST) levels had significantly improved (90.0±23.3 U⁄L versus 31.3±4.2 U⁄L; P=0.03) and mean immunoglobulin G levels had fallen (16.4±2.0 g⁄L versus 11.5±1.1 g⁄L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects. CONCLUSIONS: Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.