Self‐limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30‐year liver transplant program

A self‐limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV‐DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end‐stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear.


Hepatitis B virus (HBV) infection is a global health burden and about
2 billion subjects had contact to HBV while 248 million are chronic carriers of hepatitis B surface antigen (HBsAg) leading to liver cirrhosis and hepatocellular carcinoma (HCC). 1,2 An acute self-limited hepatitis B infection represents a recovery state: symptoms have passed, HBsAg is no longer detectable, and the patient is positive for HBc and HBs antibodies. 3 Self-limited acute HBV infection has been reported previously to be associated with abnormal liver histology even a decade after complete recovery because of the persistence of the covalently closed circular DNA (cccDNA) which is made responsible for inflammation and fibrogenesis potentially leading to the end-stage liver disease (ESLD). 4 Hepatitis B core antibody (anti-HBc) carriers may experience HBV reactivation under immunosuppression or cytostatic therapy especially undergoing bone marrow transplantation. 5,6 Transplantation of anti-HBc-positive livers may lead to HBV reactivation in up to 48%, potentially proving the relevance of cccDNA. 7 However, in patients with a history of a self-limited HBV infection and ESLD for other reasons requiring liver transplantation (LT), the main source of HBV is removed by the hepatectomy. According to the literature and current guidelines, there is no evidence that patients who undergo LT for an ESLD not related to chronic HBV infection but with a history of self-limited HBV infection (anti-HBc-positive) may experience HBV reactivation, leading to a wide variation in the clinical management. 5 Furthermore, data on HBV reactivation in patients with hepatitis C virus coinfection undergoing antiviral treatment for HCV after LT are also limited. The aim of our study was to determine the risk for HBV reactivation in patients with self-limited HBV infection prior to LT based on data from our cohort of LT patients from a 30 years LT program in Berlin.

| PATIENTS AND ME THODS
Demographic, clinical, and laboratory data were extracted from a prospectively organized database of the liver transplant program at Charité, Berlin, Germany existing since 1988. Patients with a complete data set regarding the hepatitis B serology of the donor and recipient (n = 1273) at the moment of LT were followed up regularly

| RE SULTS
The cohort (n = 1273) was divided according to the anti-HBc status   Figure 3. There was no survival differences regarding NA prophylaxis as well (P = .818).

| D ISCUSS I ON
In prophylaxis. However, the number of patients in these studies was low to definitely answer the question (n = 27 and n = 55). 16,17 To our best knowledge, this is the largest study that accurately determines the risk of HBV reactivation in a homogenous cohort of LT patients and gives a clear answer that NA prophylaxis is unnecessary in these patients.
HBV reactivation in anti-HBc-positive patients is occasionally reported after HCV treatment with DAAs. 18

| CON CLUS ION
In the present analysis, we could not confirm a risk for HBV reactivation after LT in patients with a history of a self-limited HBV infection prior to LT. Since an HBV reactivation has not been observed during the long follow-up period in a large group of patients without prophylactic NA use, our study confirms that a prophylactic use of NA is not necessary.