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Treatment of HBV-Recurrence After Liver Transplantation – 30 Years of Experience

Introduction Hepatitis-B-(HBV)-associated end stage liver disease has been one of the main indication for liver transplantation (LT) for the last decades. After LT, a HBV-reinfection remains as a serious issue and preventing strategies range from the sole application of hepatitis-B immunoglobulins (HBIG) during the anhepatic phase, to modern nucleotide analogues in combination with HBIG and later HBIG-discontinuation. The aim of the analysis was to evaluate different prophylaxis strategies and to sum up the results of 30 years at a high volume transplant center. Patients and Methods We performed 372 liver transplantations due to a HBV-associated liver disease at our clinic sinca 1988. Demographic, clinical, biochemical and histological data was extracted from a prospectively organized data base. The median follow up was 13 years. We evaluated indication for transplantation, serological status and age at time of transplantation, type of prophylaxis, stage of fribosis at 1, 3, 5, 7, 10 and 13 years after LT. The incidence and time of HBV-reinfection were investigated and analyzed. Primary endpoint was the survival depending on the type of prophylaxis. Results Among 372 LTs we identified 109 (29.3%) HBV-reinfections. HBV-reinfections after LT were significantly more frequent in male patients (84.4% vs. 73.4% in the group of with no reinfections, p=0.022). Furthermore, patients with an acute liver failure due to HBV-infection (11.0% vs. 2.8%, p=0.028) were at a significantly lower risk for a reinfection after LT as well as patients with a HCV-coinfection (11.4% vs. 4.6%, p=0.047). No significant differences in the distribution of HBV-reinfection could be observed regarding the presence of HCC (24.7 vs. 30.1; p=0.388) and HDV-co-infection (23.3 vs. 29.8%; p=0.474). Re-transplantation was not a significant risk factor for a reinfection, but the HBV-associated graft loss was significantly higher in the group of patients with a HBV-reinfection (7.3% vs. 1.9%, p=0.000). Patients with HBV-reinfection demonstrated a significantly poorer survival than patients without reinfection (log rank; p=0.004). Controlled HBV-reinfection did not demonstrated any fibrosis progression during a median histological follow-up of 13 years. Reinfection did not significantly influence the survival in patients who received NUCs and HBIG (log rank; p=0.233) compared to patients who received HBIG or nothing at all as HBV-prophylaxis (log rank; p=0.004). HBIG-discontinuation was initiated in 67 patients with just 1 patient with HBV-recurrence. Conclusion Female gender, acute liver failure for transplant indication as well as a HCV-coinfection had a lower risk for HBV-reinfection. Hbs-Ag –positive grafts did not develop fibrosis during a long-term follow up. The most reliable mode to prevent HBV-recurrence is still the combination of NUCs with a high genetic barrier and HBIG. HBIG can safely be discontinued after a still undetermined period of time after liver transplantation.