Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable hepatic replication in patients with baboon liver transplants

The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end‐stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc., A Wiley Compan

Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune‐suppressing and anticancer drugs: Just the tip of the iceberg?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110606/1/hep27609.pd

Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B

The primary aim of this study is to determine whether treatment with lamivudine improved pre–liver transplantation (pre-LT) and LT-free survival of patients awaiting LT for hepatitis B virus (HBV)-related cirrhosis. Data from 162 lamivudine-treated and 147 untreated transplant candidates managed at 20 North American transplant centers between 1996 and 1998 were collected and compared. Lamivudine-treated patients were more likely to be men, hepatitis B e antigen positive, HBV DNA positive, and have lower serum albumin levels at listing ( P < .05). Actuarial pre-LT and LT-free survival were similar in lamivudine-treated and untreated patients. Using Cox regression analysis, the only significant predictor of pre-LT patient survival was the modified Child-Turcotte-Pugh (mCTP) score, whereas significant predictors of LT-free survival included ethnic background, lamivudine treatment, indication for LT, baseline serum alanine aminotransferase level, and baseline mCTP score. Lamivudine had no apparent effect on liver disease severity in patients undergoing LT, but appeared to improve disease severity in patients still awaiting LT. Breakthrough infection was noted in 11% of lamivudine-treated patients. We conclude that lamivudine therapy is not associated with improved pre-LT or LT-free survival in LT candidates with chronic hepatitis B. However, a subset of patients with less advanced liver failure may derive clinical benefit from lamivudine therapy, thus delaying the need for LT. In the absence of prospective, randomized, controlled trials of lamivudine in patients with decompensated cirrhosis, careful selection of patients and optimal timing of treatment are needed to balance the risk versus benefit of lamivudine therapy in LT candidates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35281/1/500080503_ftp.pd

Should antiviral treatment be extended to patients with chronic hepatitis B and mildly elevated alanine aminotransferase?

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69198/1/23496_ftp.pd

Two distinct subtypes of hepatitis B virus–related acute liver failure are separable by quantitative serum immunoglobulin M anti‐hepatitis B core antibody and hepatitis B virus DNA levels

Hepatitis B virus (HBV)‐related acute liver failure (HBV‐ALF) may occur after acute HBV infection (AHBV‐ALF) or during an exacerbation of chronic HBV infection (CHBV‐ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti–hepatitis B core antibody (anti‐HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV‐ALF from CHBV‐ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV‐ALF and 27 for CHBV‐ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti‐HBc levels, and real‐time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV‐ALFs had much higher IgM anti‐HBc titers than CHBV‐ALFs (signal‐to‐noise [S/N] ratio median: 88.5; range, 0‐1,120 versus 1.3, 0‐750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV‐ALFs and 16 of 23 (70%) CHBV‐ALFs; the area under the receiver operator characteristic curve was 0.86 ( P < 0.001). AHBV‐ALF median admission VL was 3.9 (0‐8.1) log10 IU/mL versus 5.2 (2.0‐8.7) log10 IU/mL for CHBV‐ALF ( P < 0.025). Twenty percent (12 of 60) of the AHBV‐ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV‐ALF patients experienced HBsAg clearance. Rates of transplant‐free survival were 33% (20 of 60) for AHBV‐ALF versus 11% (3 of 27) for CHBV‐ALF ( P = 0.030). Conclusions: AHBV‐ALF and CHBV‐ALF differ markedly in IgM anti‐HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis. (H EPATOLOGY 2011)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90152/1/24732_ftp.pd

Meta‐analysis: oral anti‐viral agents in adults with decompensated hepatitis B virus cirrhosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90203/1/apt4990.pd

Drug Therapy: Tenofovir

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77976/1/23788_ftp.pd