Epidemiological characteristics of de novo hepatitis B infection in liver transplant recipients—An experience from a tertiary care centre in Qatar

Background The emergence of hepatitis B surface antigen in a patient with previously negative hepatitis B virus (HBV) serology post-orthotropic liver transplant (OTLX) is known as de novo hepatitis B (DNHB). As there are no data on patients with DNHB available from Qatar, we aim to do a pioneer study indexing their clinical profile and epidemiology of patients with DNHB in Qatar. Materials and Methods This descriptive epidemiological study was done by retrospectively reviewing records of 159 post-OTLX patients. HBV serology of these patients post-OTLX was reviewed, and 17 were identified as DNHB cases. Baseline epidemiological characteristics were defined and compared between DNHB cases and the rest. DNHB cases were analyzed statistically using the chi-square test and Kaplan-Meier curve. Results The majority of the subjects were men (65%) and Qataris (40%). Mean age was 57.4 ± 12.5 years. Bulk of them underwent OTLX in China (44%). The overall incidence of DNHB was 10.7%, with transplants in China having significantly higher incidence than transplants from all other countries. The mortality rate was 23.5% in DNHB cases compared to 2.8% in non-DNHB. 67% of patients survived at least 64 months after the diagnosis of DNHB. Five-year survival did not vary significantly between those with DNHB and those without. Conclusion Orthotropic liver transplant in centers selecting donors liberally without screening for HBV poses the risk of DNHB. We recommend having protective levels of HBs antibodies before OTLX. Prophylactic antiviral treatment should be considered until peri-operative HBV transmission has been excluded by screening hepatic tissue for HBV DNA. Other Information Published in: Transplant Infectious Disease License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1111/tid.13444</p

Incidence of safety-related dose reductions or discontinuations (sr-RD) (A) and SVR24 rates (B) according to the number of baseline risk factors for sr-RD in the overall population (N = 2881).

Patients with missing data (n = 300) for risk factors were excluded (BMI n = 18; HCV genotype n = 23; baseline hemoglobin n = 45; baseline platelets n = 56; baseline neutrophils n = 245). Baseline risk factors for sr-RD based on results of Cox proportional hazards analysis include: female sex, age >50 years, body mass index ≤22 kg/m2, HCV G1 or 4 infection, presence of cardiovascular disease, presence of pulmonary disease, hemoglobin ≤140 g/L, platelets ≤115 x 109/L, neutrophils ≤2.0 x 109/L.</p

Baseline characteristics of patients included in the analyses.

Baseline characteristics of patients included in the analyses.</p

SVR rates according to exposure and baseline prediction score in subgroup 2.

<p>SVR rates according to exposure and baseline prediction score in subgroup 2.</p

Multiple logistic regression analysis of baseline and on-treatment factors associated with SVR24 in Caucasian, treatment-naive, G1, noncirrhotic patients assigned to 48 weeks of treatment with PegIFN alfa-2a/RBV.

<p>Patients who discontinued therapy for efficacy or other non-safety reasons were excluded. ^aEffect P-value: P = 0.0316 for sr-RD and 0.0001 for missed ribavirin days in percentage of target.</p

Cox proportional hazards analysis for time to first safety-related dose reductions or discontinuations in patients treated for 24 or 48 weeks with peginterferon alfa-2a or alfa-2b and ribavirin.

<p>(A) All treatment-naive patients (G1–6) assigned to 24 or 48 weeks of treatment with peginterferon alfa-2a or alfa-2b/RBV (N = 3181); (B) Subgroup 2: treatment-naive Caucasian, G1 noncirrhotic patients assigned to 48 weeks of treatment with peginterferon alfa-2a/RBV (n = 951).</p

Enrollment and patient disposition.

<p>^aOther reasons (more than one reason may apply to a given patient): no final confirmation from the investigator (n = 56); contraindications to therapy (n = 15); HCV RNA-negative at screening/baseline (n = 12); end-stage renal disease (n = 7); major organ transplantation (n = 2); not treated with peginterferon alfa (n = 1) or ribavirin (n = 2); acute hepatitis C (n = 1); co-infection with HIV (n = 115); co-infection with HBV (n = 74); treatment with regimen other than peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin (n = 14); treatment-naive and intended treatment duration of 72 weeks (n = 6).</p

Scoring system used to identify patients in subgroup 2^a with a high or low probability of achieving SVR24.

<p>Scoring system used to identify patients in subgroup 2<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151703#t001fn001" target="_blank">^a</a> with a high or low probability of achieving SVR24.</p

SVR24 rates by baseline predictive score and by incidence of safety-related dose reductions or discontinuations by Week 4 and Week 12 of treatment in subgroup 2 (Caucasian, treatment-naive, G1 noncirrhotic patients assigned to 48 weeks of treatment with peginterferon alfa-2a/ribavirin).

<p>Fisher’s exact test, two-sided P-value. Please note that 34 patients had unknown baseline score.</p

SVR24 rates by incidence of safety-related dose reductions or discontinuations by Week 4 and Week 12 of treatment in genotype 1 patients assigned to 48 weeks of treatment with peginterferon alfa-2a/ribavirin.

<p>Fisher’s exact test, two-sided P-value. (A) Subgroup 1: all treatment-naive genotype 1 patients (n = 1497); (B) Subgroup 2: treatment-naive, genotype 1, noncirrhotic Caucasian patients (n = 951).</p