Hepatitis B immunoglobulin and/or nucleos(t)ide analogues for prophylaxis against hepatitis b virus recurrence after liver transplantation: A systematic review

Abstract

A combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NUCs) is currently recommended as prophylaxis against the recurrence of hepatitis B virus (HBV) after liver transplantation (LT), but the optimal protocol is a matter of controversy. The aim of this study was the identification of factors associated with post-LT HBV recurrence in patients receiving HBIG and NUCs. We searched MEDLINE and PubMed for studies in English about the effectiveness of HBIG and NUCs [lamivudine (LAM) and/or adefovir dipivoxil (ADV)] against post-LT HBV recurrence (January 1998 to June 2010). Forty-six studies, which included 2162 HBV LT recipients, met the selection criteria. Patients receiving HBIG and LAM experienced HBV recurrence more frequently than patients receiving HBIG and ADV with or without LAM [6.1% (115/1889) versus 2.0% (3/152), P ¼ 0.024], although they also were more frequently treated with indefinite HBIG prophylaxis (90% versus 57%, P < 0.001). For patients receiving HBIG and LAM, a lower frequency of HBV recurrence was associated with a high HBIG dosage (!10,000 IU/day) versus a low HBIG dosage (<10,000 IU/day) during the first week after LT [3.2% (14/440) versus 6.5% (80/1233), P ¼ 0.016], but the HBIG protocol had no impact on HBV recurrence in patients receiving HBIG and ADV. In conclusion, in comparison with the combination of HBIG and LAM, the combination of HBIG and ADV is associated with a lower rate of HBV recurrence after LT. Patients receiving HBIG and LAM should be given a high dosage of HBIG during the first week after LT, but a lower dosage can be used safely in patients receiving HBIG and ADV. Further studies with newer and more potent anti-HBV agents are definitely required. Liver Transpl 17:1176-1190, 2011. V C 2011 AASLD.Received April 10, 2011; accepted May 27, 2011.Despite the dramatic improvements in the treatment of patients with hepatitis B virus (HBV) over the last decade, chronic HBV infections are still associated with increased morbidity and mortality rates.1 Longterm treatment with nucleos(t)ide analogues (NUCs) results in stabilization and even improvement for most patients with decompensated HBV cirrhosis and thus significantly reduces the need for liver transplantation (LT) for HBV-induced chronic liver failure.2,3 However, hepatocellular carcinoma may still develop in patients with cirrhosis after several years of treatment-induced virological remission 4 and is currently the most common cause of LT in patients with chronic HBV.In the early 1990s, the introduction of long-term hepatitis B immunoglobulin (HBIG) use significantly reduced the rate of posttransplant HBV recurrence and improved the prognosis of patients; LT became practical for many patients with HBV-related end-stage liver

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“…28 This can be largely attributed to the greatly reduced recurrence rate of hepatitis after liver transplant in patients with HBV infection after the introduction of prophylactic therapy in the form of either lamivudine and hepatitis B immunoglobulin or entecavir and hepatitis B immunoglobulin. 9,21,[32][33][34][35] We found significantly low patient and graft survival in patients with both HBV and HCV in our study; this finding is similar to the results of Waki and associates, 36 who analyzed data from the United Network for Organ Sharing for liver graft survival in patients with different types of viral hepatitis and found that recipients with HBV had the highest graft survival compared with patients with HCV infection or patients with combined HBV and HCV. In our study, we only had 5 patients with combined HBV and HCV; all of these patients had fulminant hepatic failure and 4 had concomitant HCC, which resulted in worse prognosis.…”

The detection of (total and ccc) HBV DNA in liver transplant recipients with hepatitis B vaccine against HBV reinfection

“…The combination prophylaxis with antiviral agents and HBIG reduces the HBV recurrence rate to 5% at 5 years, which is now almost universally adopted by most transplant centers as the golden standard for the prevention of HBV reinfection. 4 However, passive immune prophylaxis with long-term administration of HBIG is associated with many issues, including the limited availability of HBIG, possible emergence of HBV envelope protein mutations, 5 development of resistance to nucleotide analogs 6 and, especially, extremely high costs. 7 The ideal prophylactic strategy is to stop prophylaxis with HBIG when HBV infection had been completely cleared.…”

Evidence-based clinical practice guidelines for liver cirrhosis 2015

“…Although nucleoside analogues are useful for preventing hepatitis B recurrence, the recurrence rate was lowest in patients who received combined hepatitis B immunoglobulin plus nucleoside analogue prophylaxis (6.6 %) compared with those receiving nucleoside analogue prophylaxis alone (19.0 %) or hepatitis B immunoglobulin prophylaxis alone (26.2 %) [234]. The combination of hepatitis B immunoglobulin and ADV was more effective than hepatitis B immunoglobulin plus LDV prophylaxis [234].…”