Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection

Saidy, Ramin Raul Ossami; Sud, Irina; Eurich, Franziska; Aydın, Mustafa; Postel, M; Dobrindt, Eva Maria; Pratschke, Johann; Eurich, Dennis

doi:10.3390/v13050904

Cited by 5 publications

(5 citation statements)

References 23 publications

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“…Besides the fact that HDV‐coinfected patients have a low replication of HBV, which, by definition, puts them in a low‐risk for recurrence group, available data, together with our current findings, show that HBIg discontinuation while continuing on NA is not associated with reactivation of HDV from the latent state. To date, 99 LT recipients from various series have already been reported to have discontinued HBIg, with variable lengths of follow‐up, while being continued on NA 11,12,23–26 . Only three showed HDV recurrence, including one who received the liver from an HBsAg positive donor graft.…”

Section: Discussionmentioning

confidence: 99%

“…To date, 99 LT recipients from various series have already been reported to have discontinued HBIg, with variable lengths of follow-up, while being continued on NA. 11,12,[23][24][25][26] Only three showed HDV recurrence, including one who received the liver from an HBsAg positive donor graft. Importantly, no HDV recurrences were observed in the other 11 patients from these series who became HBsAg positive after HBIg discontinuation.…”

Section: Discussionmentioning

confidence: 99%

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Successful clinical and virological outcomes of liver transplantation for HDV/HBV‐related disease after long‐term discontinuation of hepatitis B immunoglobulins

Lenci

Tariciotti

Manzia

et al. 2023

Clinical Transplantation

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Background Indefinite, long‐term administration of hepatitis B immunoglobulins (HBIg), together with a third generation nucleos(t)ide analog (NA), is the currently recommended prophylactic strategy to prevent viral recurrence after liver transplantation (LT) for Hepatitis Delta virus (HDV)/Hepatitis B virus (HBV)‐related disease. Methods We retrospectively analyzed the safety and long‐term clinical and virological outcomes of a consecutive cohort of 16 patients (10 males, median age 64.5, range 41–75) transplanted for HDV/HBV‐related cirrhosis at our Institution, who discontinued HBIg after a median of 24.5 months (range 15–116) after transplant. All patients continued prophylaxis with same NA used before LT. Recurrence of HDV/HBV infection was defined as reappearance of serum HDV‐RNA with detectable serum HBsAg and/or HBV‐DNA. Results The median follow‐up after LT was 138 months (range 73–316) and 110 months (range 52–200) after HBIg withdrawal. All patients were HBsAg‐positive, HBV‐DNA negative, and anti‐HDV positive at the time of LT and without coinfections with HCV or HIV. Patients were followed with biochemical and virological tests every 3–6 months after HBIg withdrawal. No recurrences of HDV/HBV infection or disease were observed during monoprophylaxis with NA. In addition, eight patients (50%) spontaneously developed anti‐HBs titers above 10 IU/L at a median of 74 months (range 58–140) following HBIG discontinuation. Conclusions HBIg withdrawal after LT is a safe and efficacious strategy in patients transplanted for HDV/HBV disease and is frequently associated with the spontaneous development of serological immunity against HBV. These data call for a revision of current prophylactic recommendations in this setting.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Successful clinical and virological outcomes of liver transplantation for HDV/HBV‐related disease after long‐term discontinuation of hepatitis B immunoglobulins

Lenci

Tariciotti

Manzia

et al. 2023

Clinical Transplantation

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“…Thirty-four, 25, and 17 HDV recipients recruited by Cholongitas et al, 49 Öcal et al, 51 and Ossami Saidy et al 47 were initially given prophylaxis with HBIg and NA and then discontinued HBIg and were followed for 12 to 58 mo (median 28), 3 to 120 mo (median 59), and 6 to 360 mo (median 120), respectively. Two patients became HDV reinfected in the series of Cholongitas; however, one received the liver from a HBsAg-positive donor, and reinfection was virtually inevitable.…”

Section: Perspectives Of Prophylaxismentioning

confidence: 99%

“…HDV patients NA after HBIg discontinuation Follow-up after HBIg discontinuation median (range) HBV/HDV recurrence Ossami Saidy et al 47 17 LAM or ETV or TDF 120 mo (6-360 mo) 5 HBV recurrence and 1 HDV recurrence Manini et al 39 8 ETV or TDF 61 mo (31-78 mo) 0 Caccamo 48 5 LAM 20 y (18-20 y) 0 Cholongitas et al 49 arises about the future of HDV transplant in high-income countries where LT centers are more numerous and more active.…”

Section: Referencesmentioning

confidence: 99%

Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients

et al. 2022

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Hepatitis D is caused by the hepatitis D virus (HDV); it is the most severe form of viral hepatitis in humans, running an accelerated course to cirrhosis. There is no efficacious therapy, and liver transplantation provides the only therapeutic option for terminal HDV disease. However, HDV infection is prevalent in poor countries of the world with no access to liver transplant programs; liver grafting has been performed in high-income countries, where the prevalence of the infection has much diminished as a secondary effect of hepatitis B virus vaccination, and the demand for liver transplantation outlives in aging cirrhotics who acquired hepatitis D decades ago. This review describes the evolution of liver transplantation for HDV disease from its inception in 1987 to the present time, with an outlook to its future. It reports the progress in the prophylaxis of HDV reinfections to the success of the current standard of indefinite combination of hepatitis B virus antivirals with immunoglobulins against the hepatitis B surface antigen; however, the unique biology of the virus provides a rationale to reducing costs by limiting the administration of the immunoglobulins against the hepatitis B surface antigen.

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“…In a study from Germany 21 , the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV‐/HDV‐associated end‐stage liver disease was evaluated retrospectively. Seventeen patients eventually discontinued HBIg therapy for various reasons with a median time after LT of 72 (0–312.0) months.…”

Section: Is Hepatitis B Immunoglobulins Immunoprophylaxis Needed Afte...mentioning

confidence: 99%

Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins?

Ferenci

Reiberger

Stadlbauer

et al. 2022

Liver International

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The introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long‐term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short‐term (i.e. 4–8 weeks) HBIg prophylaxis after LT followed by the long‐term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co‐infected patients, the need for long‐term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post‐LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10–13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post‐LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post‐LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co‐infection did not lead to impaired overall survival or a higher recurrence rate in this long‐term follow‐up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended.

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Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection

Cited by 5 publications

References 23 publications

Successful clinical and virological outcomes of liver transplantation for HDV/HBV‐related disease after long‐term discontinuation of hepatitis B immunoglobulins

Successful clinical and virological outcomes of liver transplantation for HDV/HBV‐related disease after long‐term discontinuation of hepatitis B immunoglobulins

Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients

Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins?

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