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BACKGROUND & AIMS: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS: We collected data from the Hepatitis B Research Network—an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS: ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th–75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P

PURPOSE OF REVIEW To increase awareness and review the management of chronic viral hepatitis in individuals treated with immune-modifying agents to avoid potentially severe consequences. RECENT FINDINGS Hepatitis B virus (HBV) reactivation has been reported with a wide variety of immunosuppressive regimens ranging from corticosteroids to cytotoxic chemotherapy. In the rheumatology field, reactivation is best studied with anti-tumor necrosis factor-alpha agents and may occur even in individuals with 'resolved' HBV infection. These complications can be prevented with the use of well tolerated pre-emptive antiviral agents. Treatment of reactivation after it occurs is much less effective. Unlike HBV, acute deterioration is rare with immunosuppression in patients with hepatitis C virus (HCV) and prophylactic therapy is not indicated in these patients. However, patients should undergo evaluation for staging of liver disease preferably before immunosuppression because of the risk of drug-induced liver injury and also rheumatological complications, such as cryoglobulinemia. SUMMARY HBV and HCV remain enormous global health problems with over 500 million people infected worldwide. Neither virus is cytopathic with liver damage and control of viral replication caused by the host immune response. With the increasing number and types of immunomodulatory therapies, HBV reactivation is becoming an increasingly recognized issue in many areas of medicine, particularly rheumatology. Unfortunately, screening rates are low, partially because of unclear clinical guidelines. HCV may also complicate immunomodulatory therapy, particularly if cirrhosis is present. The management of rheumatology patients with HBV and HCV infection is discussed with a focus on whom to screen and whom to treat to prevent consequences of these often unrecognized conditions.

Background & Aims T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). Methods We enrolled 200 adults with CHB who participated in the National Institutes of Health−supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. Results Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3 + CD127 − regulatory T cells and CD4 + T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg) + than HBeAg − patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte-associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg + than HBeAg − patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. Conclusions HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell−based immune signatures for clinical phenotypes. These findings suggest additional T-cell−independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.

169 Background: Hepatitis B virus (HBV) reactivation is a potentially fatal complication of cancer therapy that is almost entirely preventable. Despite this, HBV screening rates remain low at many centers. We evaluated the effectiveness of an electronic prompt on HBV screening rates and compared this strategy with education alone. Methods: An education session on HBV reactivation was delivered to all oncology staff at two large, academic oncology centers in the fall of 2010. At one center (study center) an electronic prompt was also introduced. The electronic prompt reminded physicians to screen for HBV when booking a new patient’s first chemotherapy and automatically trigged an electronic order for HBsAg if the physician assented. The prompt was not implemented at the second (control) center. The primary endpoint was the rate of HBV screening. Actual HBV screening rates were determined in both centers for 10 months prior to and for 12 months following the interventions. HBV screening rates were assessed and compared with process control charts (p-charts); 3-sigma limits were employed to define special cause variation. Results: 6,116 new patients received their first chemotherapy during the study period (2,095 study center; 4,021 control center). In the pre-prompt period, the screening rate was stable at 16% at the study center and 25% in the control center. In the prompt period, the screening rate increased to 62% at the study center and was unchanged at 25% in the control center. Special cause variation suggesting a non-random improvement in HBV screening rate was detected at the Study Center two months after the introduction of the electronic prompt. Conclusions: An electronic prompt increased the rate of HBV screening, however screening rates remained relatively low. Education sessions did not appear to improve the HBV screening rate.

6627 Background: Hepatitis B virus (HBV) reactivation is a potentially fatal and yet preventable complication of myelosuppressive therapy. However, HBV screening rates have been low despite the rec...