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Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5-and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P ‫؍‬ NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P ‫؍‬ .0003). options. The introduction of high doses of hepatitis B immune globulins (HBIG) or of lamivudine (LAM) as post-LT mono-prophylaxis has reduced the risk of hepatitis B recurrence to a variable cumulative rate ranging between 10% and 50%. During prophylaxis with LAM or HBIG a strict correlation between hepatitis recurrence and hepatitis B virus (HBV) DNA load at the time of surgery has been found, which is related to the emergence of viral mutants that are unresponsive to therapy, such as surface antigen (HBsAg) mutants and tyrosine-methionine-aspartate-aspartate (YMDD)-mutants. 1 -5 Moreover, neither HBV recurrence nor graft failure have been observed in patients with HBV DNA undetectable by polymerase chain reaction at the time of surgery and treated with HBIG. 6 The risk of hepatitis B recurrence can be reduced to less than 10% by using LAM before and after LT, in association with HBIG. 7 -13 Moreover, although LAM therapy before transplantation can improve liver function and decrease mortality, 14 long-term antiviral therapy can select YMDD mutants whose management needs the use of alternative drugs, such as adefovir dipivoxil (ADV), to reduce HBV recurrence after LT. 15 -19 However, a variety of issues still remain controversial. In particular, doubts remain as to what virological status has to be achieved in patients undergoing LT and which HBV DNA assays have to be performed. This study analyzes 177 HBsAg carriers who underwent transplantation in a single center between 1990 and 2002 with the aim of evaluating the prognostic role of the HBV DNA viral load at the time of surgery on the risk of hepati...

The combination of lamivudine and hepatitis B immunoglobulin (HBIG) reduces the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the efficacy of this strategy and the need for combined therapy with adefovir dipivoxil (ADV) in patients who select lamivudine-resistant strains (YMDD) before surgery is still unknown. Twenty-two patients treated with lamivudine (LAM) who underwent LT after YMDDmutant selection were studied. In 13 patients, YMDD mutants were associated with an HBV DNA breakthrough greater than 5 log 10 (group A: phenotypic resistance), and 11 were treated with ADV to decrease viral load before LT. In the remaining 9 patients who did not experience the viral breakthrough, YMDD mutants were detected only retrospectively in sera stored at the time of LT (group B: genotypic resistance). During 35 months of post-LT follow-up, none of the 11 patients of group A treated with ADV before and after surgery (in addition to HBIG and LAM) had HBV recurrence, and neither did any of the 7 subjects of group B treated with LAM before and after transplantation (in addition to HBIG). HBV recurred in 2 patients of group A (untreated with ADV before surgery and transplanted with an HBV DNA exceeding 5 log 10 ) and in 2 subjects of group B (who spontaneously stopped HBIG after surgery). In carriers of YMDD mutants, the risk of post-LT HBV recurrence is low, provided that preemptive and prophylactic ADV (in addition to LAM and HBIG) treatment is used in highly viremic patients and prophylactic LAM (or ADV) and HBIG therapy is continued in low viremic patients. (Liver Transpl 2005; 11:532-538.) I n hepatitis B virus (HBV) DNA-positive patients, the rate of HBV recurrence after liver transplantation (LT) remains significant (50%-90%) despite monoprophylaxis with hepatitis B immunoglobulins (HBIG) or with lamivudine (LAM). In both cases, post-LT HBV recurrence may be associated with the appearance of viral mutants selected by either HBIG or LAM, whose occurrence appears correlated with the serum levels of HBV DNA at the time of LT. [1][2][3][4] Resistance to LAM is characterized by the substitution of methionine with valine or isoleucine at residue 204 (formerly 552) within the tyrosine-methionineaspartate-aspartate (YMDD) motif of the viral DNA polymerase. This mutation results in a more than 10,000-fold decrease in sensitivity to LAM treatment in vitro. 5 The clinical lack of virologic response to LAM associated with the YMDD mutants is currently defined by a viral breakthrough with HBV DNA greater than 5 log 10 copies/mL. 6,7 In the transplant setting, the appearance of the YMDD mutant during posttransplantation LAM prophylaxis is frequently associated with recurrence of the hepatitis B surface antigen (HBsAg) and liver disease in the graft. 3 Although combined prophylaxis with LAM and HBIG is effective in preventing HBV recurrence after LT, [8][9][10][11][12][13][14] whether it is equally effective in transplant candidates who have developed YMDD mutants before transplantation is not cl...

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Combination therapy (Interferon plus ribavirin) is the current therapeutic gold standard for naive Hepatitis C Virus (HCV)-positive patients and with the recent advent of pegylated (PEG) IFN the rate of the sustained virological response (HCV-RNA clearance 6 months after the end of treatment) is about 54%-56% with a therapeutical gain mainly among patients with unfavourable HCV genotype (1a, 1b); in this subset of patients, a 42%-46% sustained response rate is achieved compared with 33%-36% found among genotype 1 patients treated with the standard therapy. Patients who respond to IFN monotherapy but relapse during the follow-up should be re-treated with combination therapy given for at least 6 months at the minimum dose of 3 MU thrice weekly plus ribavirin 1000 mg/daily. Recent data suggest that prolonging the time of treatment (12 months) may induce a significantly higher rate of sustained response among patients with genotype 1. The efficacy of the combination of IFN and ribavirin in retreating patients with chronic hepatitis C not responding to IFN monotherapy is controversial as it ranges between 0% and 40%. Recent data show an overall rate of sustained response of 23% when an aggressive approach is adopted but increasing the dosage and the time of treatment induces a significant therapeutic benefit only in patients with genotype 1. In conclusion, a therapeutic progress for chronic hepatitis C has been achieved during the last 10 years (56% vs 20% of sustained response rate obtained with IFN monotherapy) but several unresolved issues are yet to be addressed.