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Letters to the Editor

An Experiment of Nature: HBV-naive Recipients Receiving Liver Grafts With HBV Core Antibody-positive Donors Without Antiviral Prophylaxis

Fallahzadeh, Mohammad Amin MD, MPH1; Trotter, James F. MD1

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doi: 10.1097/TP.0000000000003233
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Transplantation of livers from donors who are hepatitis B core antibody (HBcAb) positive and hepatitis B surface antigen (HBsAg) negative is a standard practice occurring in about 5% of the US liver transplants (LTs).1,2 Current guidelines recommend lifelong oral antiviral prophylaxis to prevent viral reactivation reported in up to 78% of untreated recipients.1,3 We report a series of HBsAg-negative LT recipients who received an organ from HBcAb-positive donors without receiving antiviral prophylaxis through an administrative error.

HBsAg-negative LT recipients at Baylor University Medical Center in Dallas of Simmons Transplant Institute receiving grafts from HBcAb-positive donors without antiviral prophylaxis from 1997 to 2017 were evaluated by chart review. Out of 2521 LTs, 122 (4.8%) recipients with HBcAb-positive donors were identified that 14 of them (11.5%) did not receive any postoperative antiviral prophylaxis (Table 1). Also, these patients did not undergo the routine hepatitis B virus (HBV) testing of recipients with HBcAb-positive donors at 90 d post-LT. Before LT, all the 14 patients were HBsAg and HBV DNA negative and only 1 recipient was HBcAb positive. HBsAb was measured in 11 patients before LT: 8 patients were HBsAb positive (7 of 8 following vaccination and 1 of 8 due to prior infection with no HBsAb titer measurement) and 3 were negative. The median follow-up duration was 7.2 y (range: 1–22 y). Most patients (11 of 14) were prescribed tacrolimus and mycophenolic acid for post-LT immunosuppression. Two out of 14 patients (14.3%) developed asymptomatic HBV viremia with positive HBsAg 1.7 and 2.1 y post-LT. Both of these patients had negative pretransplant HBsAb, and none of the patients with pretransplant HBsAb developed HBV viremia. During follow-up, only 1 patient died 9.6 y after his LT because of colon perforation in the context of ischemic colitis. This patient had negative HBsAg and HBV DNA in his last follow-up.

TABLE 1.
TABLE 1.:
Baseline characteristics of 14 liver transplant recipients receiving HBcAb-positive livers without antiviral prophylaxis

Our results are similar to other studies from areas with greater HBV prevalence than the United States with only 7.7%–9.5% of such recipients developing HBV viremia.4,5 However, the rate of HBV viremia in our study is lower than historically reported in the United States.1,3 The explanation for such low rates could be due to differences in recipient characteristics, primarily higher rates of HBsAb rates in the recipient population compared with 25 y ago when these studies were published. Moreover, lower rates of occult HBV infection in the donors can play a role as it has been reported that antiviral prophylaxis in such transplants could be limited to the recipients receiving a graft from a donor with detectable HBV DNA.4

In a systematic review including 903 recipients of HBcAb-positive liver grafts, 47.8% (89 of 186) of HBV-naive recipients developed de novo HBV infection. Similar to our report, this rate was lower (9.7% [3 of 31]) for the recipients with HBV vaccination before LT.1 Thus, HBV vaccination before LT is an effective measure to reduce de novo HBV infection even in the context of post-LT immunosuppression.

In conclusion, the rate of HBV viremia is lower in this small series compared with historically reported ones, especially in the United States. HBV infection has the potential to cause significant allograft dysfunction and potentially cirrhosis in the long term; thus, a conservative approach would be to continue antiviral prophylaxis if available in the recipients of anti-HBcAb-positive grafts particularly in the ones with negative HBsAb. As none of the patients with positive pretransplant HBsAb developed HBV viremia, physicians may consider these data in selecting patients for lifelong prophylaxis to avoidance of which could significantly reduce healthcare costs and incidence of drug resistance. Future prospective studies with larger sample sizes are needed to further determine the characteristics of the patients who require lifelong antiviral prophylaxis.

REFERENCES

1. Cholongitas E, Papatheodoridis GV, Burroughs AK. Liver grafts from anti-hepatitis B core positive donors: a systematic review. J Hepatol. 2010; 52:272–279doi:10.1016/j.jhep.2009.11.009
2. Huprikar S, Danziger-Isakov L, Ahn J, et al. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015; 15:1162–1172doi:10.1111/ajt.13187
3. Dickson RC, Everhart JE, Lake JR, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. Gastroenterology. 1997; 113:1668–1674doi:10.1053/gast.1997.v113.pm9352871
4. Bortoluzzi I, Gambato M, Albertoni L, et al. Use of grafts from anti-HBc-positive donors in liver transplantation: a 5-year, single-center experience. Transplant Proc. 2013; 45:2707–2710doi:10.1016/j.transproceed.2013.07.049
5. Kim HY, Choi JY, Park CH, et al. Adult living donor liver transplantation using hepatitis B core antibody-positive grafts in Korea, a hepatitis B-endemic region. Gut Liver. 2011; 5:363–366doi:10.5009/gnl.2011.5.3.363
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