Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients

<p>Abstract</p> <p>Background</p> <p>To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.</p> <p>Methods</p> <p>Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1–12, 13–24 and 24–48, respectively. Multilevel modelling was used to analyse the relationship between these variables.</p> <p>Results</p> <p>Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10⁷copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8⁺T cells and increase in CD4⁺T cells were found from week 12. Both parameters and CD4⁺/CD8⁺ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4–48 week). After 4 weeks of therapy, for each log₁₀scale decrement of HBV DNA, the percentage of CD4⁺lymphocyte was increased by 0.49 and that of CD8⁺decreased by 0.51.</p> <p>Conclusion</p> <p>T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.</p

Survival from hepatic transplantation. Relationship of protein synthesis to histological abnormalities in patient selection and postoperative management.

Forty-one patients, all in end stage hepatic failure, underwent 46 liver transplantations with a long-term survival rate of 63%. Six patients died of uncontrollable bleeding due to primary graft malfunction at or immediately after operation. Nine died early or late with overwhelming infection. In addition to clinical assessment, needle liver biopsy, central plasma clearance rate of amino acids (CPCR-AA), and routine "liver function tests" were employed to aid in selection of patients for transplantation and for guidance in postoperative management. Although liver biopsies usually afforded an exact diagnosis, neither they nor the routine liver function tests quantitated the extent to which hepatocyte function was impaired. CPCR-AA, which measures the rate of amino acid uptake by the liver and other central tissues for oxidation, gluconeogenesis, and protein synthesis was 91 +/- 9 ml/M2/min in the preoperative transplant group. This compares with a value of 97 +/- 16 in a previously studied series of cirrhotics who died following other forms of surgery and a CPCR-AA of 220 +/- 26 ml/m2/min in those who survived. In addition, the preoperative CPCR-AA was found to correlate with the in vitro hepatic protein synthetic rate of slices from the resected recipient liver (r = 0.72, p less than 0.02). After operation, serial hepatic needle biopsies were classified by histology into four grades of injury, ranging from normal liver transplant (Grade I) to mild hypoxic or rejection injury (Grade II), viral hepatitis (Grade III), and severe hypoxic or rejection injury (Grade IV). Significant relationships of the histological grades to ultimate mortality, CPCR-AA, and prothrombin times were found. CPCR-AA and prothrombin time correlate inversely (r = 0.57, p less than 0.001), further demonstrating the relationship of CPCR-AA to protein synthesis of clotting factors. These patterns of posttransplant response were delineated by serial CPCR-AA values. "Early" responders had values over 290 ml/M2/min and all survived. Twelve patients with delayed response were characterized by values of 150 +/- 12, rising to over 200 ml/M2/min after 2 weeks. Two who failed to increase CPCR-AA died. In six "poor" responders, CPCR-AA with Grade IV injury remained below 110 ml/M2/min. All died except for one whose CPCR-AA subsequently rose following retransplantation. It is concluded that percutaneous hepatic needle biopsies and CPCR-AA measurements in combination are of proven value, not only in understanding the nature of injury and functional impairment of the liver, but are also important as guides to selection of patients and for their posttransplant management

Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-alpha and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days,