Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation

Abstract

The incidence of hepatitis B (HB) recurrence after a liver transplantation has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine. However, the long-term incidence of recurrence is Ͻ10%, and the factors associated with HB recurrence are unclear. This study analyzed the factors associated with HB recurrence in 203 recipients who underwent liver transplantation for HB in 3 major centers in Korea over 4 years. Eighty-five patients (41.9%) had a hepatocellular carcinoma (HCC). Preoperative active virus replicators with the HBeAg(ϩ) (46.8%) and/or hepatitis B virus DNA(ϩ) (39.4%) were observed in 136 patients (67.0%). The HB prophylaxis consisted of either HBIG monotherapy (n ϭ 95, HBIG group) or combination therapy with lamivudine (n ϭ 108, combination group). HB recurrence was defined as the appearance of the HBsAg. The follow-up period was 28.3 Ϯ 13.1 months (mean Ϯ SD). HB recurred in 21 patients (10.3%) after transplantation. The time from transplantation to recurrence was 16.3 Ϯ 9.4 months. Pre-LT DNA positivity was more prevalent in HBIG group (55.8%) than in the combination group (39.8%) (P ϭ 0.015). However, the incidence of HB recurrence was similar in the HBIG (6.3%) and combination group (13.8%), as well as between the active replicators (12.5%) and nonreplicators (4.1%) (P Ͻ 0.05). There was a far higher incidence of HB recurrence in patients receiving corticosteroid pulse therapy (21.0% vs. 7.9%), patients who experienced HCC recurrence (31.3% vs. 8.6%), and patients receiving chemotherapy to prevent HCC recurrence (25.0% vs. 4.4%) (P Ͻ 0.05). The cumulative corticosteroid dose was higher in patients who experienced recurrence of HB (P ϭ 0.002). Multivariable analysis confirmed the effect of the cumulative corticosteroid dose and chemotherapy to be risk factors. Liver transplantation for HB is safe, with low recurrence rates if adequate prophylaxis is used. However, the cumulative corticosteroid dose and the chemotherapy used for HCC were risk factors for HB recurrence, so careful monitoring for HB recurrence is needed in these patients. Liver Transpl 13:451-458, 2007. © 2007 AASLD. Received December 19, 2005 accepted October 18, 2006.The outcome of liver transplantation (LT) for hepatitis B virus (HBV)-related liver diseases was dismal before the advent of an effective means for preventing the virtually universal reinfection of the graft. Reinfection was followed by progressive destruction by recurrent hepatitis. This led to quick graft failure. HBV-related liver disease was once considered to be a contraindication for LT. However, over the last 15 years, there have been major advances in the management of transplant candidates with hepatitis B (HB). The long-term use of

High Hepatitis B Virus DNA Level in Serum before Liver Transplantation Increases the Risk of Hepatocellular Carcinoma Recurrence

“…Several factors have been reported to be associated with an increased risk of recurrent HCC after liver transplantation including tumor size, number of nodules, vascular infiltration, differentiation, preoperative serum AFP level and the usage of glucocorticoid [4,5,11]. Our study shows that exceeding Milan criteria is a predictive risk factor of HCC recurrence, which supports the use of Milan criteria to select OLT candidates.…”

Resection of Pulmonary Metastases from Hepatocellular Carcinoma following Liver Transplantation

“…After diagnosis of HCC recurrence, the trough level of calcineurin inhibitor was decreased by half (tacrolimus \5 ng/mL, cyclosporine \ 80 lg/mL); combined therapy with calcineurin inhibitors and mycophenolate mofetil often was converted to calcineurin inhibitor monotherapy; the 24 hour trough level of sirolimus was set to be\10 ng/mL. Because HCC recurrence is an established risk factor for hepatitis B virus (HBV) infection, patients with HBVassociated HCC were administered concurrent high-dose antihepatitis B immunoglobulin to maintain anti-HBs trough level [500 IU/L and antiviral treatment (mostly entecavir), regardless of the status of HBV recurrence [22][23][24].…”

Vaccination against viral hepatitis b in pediatric liver transplant recipients

“…Для отдельных групп пациентов c высокими рисками развития HBV-инфекции рекомендованный целевой уровень антител может быть выше: 100-250 МЕ/л [30], 100-500 МЕ/л [31,32], тогда как в некоторых исследова-ниях считается достаточным уровень более 10 МЕ/л [12,23], более 20 МЕ/л [33].…”