Evidence of serious graft damage induced by de novo hepatitis B virus infection after liver transplantation

Abstract

De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is commonly believed to be a relatively benign condition, in contrast to post-OLT infection recurrence, considered a very aggressive complication. We reviewed the charts of 569 non-HBV-related OLTs performed at our institution and identified 19 patients (3%) with de novo HBV infection (appearance of hepatitis B surface antigen [HBsAg] after OLT). After a median follow-up of 25 months beyond the detection of HBsAg, 12 patients (63%) had developed serious HBVrelated graft damage (cirrhosis in 6 patients, bridging chronic hepatitis in 4 patients, and fulminant hepatitis in 2 patients); 7 patients (37%) had lost their grafts; and 4 patients (21%) had died. All graft losses and deaths were related to de novo HBV infection. Similar rates of severe graft damage (62%), graft loss (38%), and death (33%) related to HBV infection were found in a concomitant series of 21 patients with recurrent HBV infection after OLT. Responses to antiviral therapy (interferon or lamivudine) were also similar in the 2 groups of patients. In 12 patients with de novo HBV infection, evidence of past HBV infection (positive serum antibody to hepatitis B core antigen and/or serum or liver tissue HBV DNA) were detected in the donor (7 patients) or recipient (5 patients). No differences were observed in the clinical course after stratification according to the attributed origin of de novo HBV infection. We conclude that de novo HBV infection after OLT is associated with high rates of morbidity and mortality, similar to those described for post-OLT HBV infection recurrence. (Liver Transpl 2001;7:106-112.)

Case Report of Lamivudine-Resistant Hepatitis B Virus Infection Post Liver Transplantation from a Hepatitis B Core Antibody Donor

“…However, follow-up biopsies in this series revealed significant histologic recurrence in 5 out of 8 biopsies from 1.6 to 4.5 years after LT and an overall decreased 4-year survival in recipients of grafts from anti-HBc donors (1). Other authors in addition have reported more severe disease including Uemoto et al who described 15 cases with one death from fibrosis cholestatic hepatitis and two with chronic active hepatitis (3,10,41). The effect of new antiviral therapies and antiviral-resistant HBV infections on the course of de novo post-LT HBV is yet to be determined.…”

Outcomes of liver transplantation using Hepatitis B core-positive liver grafts: Implications for prophylaxis

“…All recipients were anti-HBc negative. Segovia et al [15] reported a higher and more aggressive de novo HBV infection in 12 out of 19 patients. Three recipients were anti-HBc positive, and nine were anti-HBc negative.…”

“…Despite this high rate of transmission, most studies have shown that patients with de novo HBV infection usually have a mild clinical course and infection can be prevented with prophylaxis [15,32•]. However, a recent study from Spain demonstrated that 63% of patients developed severe de novo HBV infection and 21% died, demonstrating that de novo HBV can have an aggressive course [15].…”

“…HBV infection has been reported to occur in 25% to 100% of recipients with detectable antiHBc who received an anti-HBc-positive graft [2,5,7,8,14]. De novo HBV infection can lead to severe allograft dysfunction and death [15]. Retransplantation for de novo infection is associated with a 6-month patient survival rate of 5% [16].…”

“…HBV infection in the transplant recipient can be classified as de novo or recurrent. De novo HBV infection follows a mild course, but aggressive and fulminant hepatitis can occur [15]. AntiHBc-negative recipients are at greatest risk of developing de novo HBV infection and prophylactic strategies should be used.…”