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Long‐term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years

Long‐term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long‐term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow‐up. The median duration of follow‐up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg‐positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9‐year survival was 85%. There were 37 deaths during the follow‐up period, of which none were due to hepatitis B recurrence. Conclusion: Long‐term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long‐term survival of 85% at 9 years. (Hepatology 2017;66:1036‐1044).

Outcomes including liver histology after liver transplantation for chronic hepatitis B using oral antiviral therapy alone

The outcomes of hepatitis B virus (HBV)–related hepatitis after liver transplantation (LT) without hepatitis B immune globulin (HBIG) is not well documented. This study aims to determine the outcomes of chronic hepatitis B (CHB) patients using an HBIG‐free regimen. All biopsies performed 3 months or more after LT in consecutive CHB patients transplanted from 2003 to 2012 were reviewed. None of the patients received HBIG. Results of all liver histologies were reviewed to determine the cause of graft dysfunction. Of the 435 patients transplanted during this period, 263 liver biopsies were performed in 144 patients. Thirty‐six patients were positive for hepatitis B surface antigen (HBsAg) with undetectable HBV DNA at the time of biopsy, and none had histological evidence of HBV infection. Of the 263 biopsies, 44 (17%) had evidence of fibrosis. There was a significantly higher rate of fibrosis in those with large duct obstruction compared to those without (51% versus 9%, respectively; P < 0.001). Of the 291 patients without a liver biopsy during the same period, 43 were HBsAg+. Seven patients had evidence of virological rebound, of whom 6 had evidence of rtM204V/I mutation and 1 had recurrence of hepatocellular carcinoma with low‐level rebound and wild‐type virus. In conclusion, for patients without virological rebound, positive serum HBsAg was not associated with histological evidence of HBV‐related hepatitis after LT. To prevent virological rebound, nucleos(t)ide analogues with higher barriers to resistance should be used. Liver Transpl 21:1504‐1510, 2015.

Clinical factors affecting rejection rates in liver transplantation

BACKGROUND With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection. METHOD We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors. RESULTS Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P<0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR. CONCLUSIONS Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

Oral Nucleos(t)ide Analogs Alone After Liver Transplantation in Chronic Hepatitis B With Preexisting rt204 Mutation

Background There is currently limited data regarding the use of oral antiviral therapy alone without hepatitis B immune globulin for chronic hepatitis B patients with preexisting lamivudine (LAM) resistance (LAM-R) undergoing liver transplantation. Methods This is a cohort study determining the effectiveness and long-term outcome in this group of patients. Results Fifty-seven consecutive chronic hepatitis B patients with preexisting rt204 LAM-R mutations or virological load refractory to LAM undergoing liver transplantation were included, with a median follow-up of 73 months. Fifty-five (96.5%) patients received a regimen that included the use of nucleotide analogs. The cumulative rate of hepatitis B surface antigen seroclearance at 1, 5, and 10 years was 82%, 88%, and 91%, respectively. At the time of transplantation, 39 (72%) patients had detectable hepatitis B virus (HBV) DNA, with a median of 4.5 log copies/mL. The cumulative rate of HBV undetectability was 91% at 1 year, increasing to 100% by 5 years. After 1 year of liver transplantation, over 90% of the patients had undetectable HBV DNA, and from 8 years onward, 100% had undetectable HBV DNA. The overall long-term survival was excellent, with a 12-year survival of 87%. There was no HBV-related graft loss, and no retransplantation or deaths due to HBV reactivation. Conclusion Oral antiviral therapy alone without hepatitis B immune globulin is highly effective in preventing HBV reactivation and graft loss from recurrent hepatitis B after liver transplantation in patients with preexisting LAM resistance HBV. The long-term outcome was excellent, with survival of 87% at 12 years after transplantation, without any mortality related to HBV reactivation.

Liver transplantation: a life-saving procedure following amatoxin mushroom poisoning

In April 2013, a 48-year-old man and his wife picked wild mushrooms near Shing Mun Reservoir. After eating the cooked mushrooms, they developed symptoms resembling gastroenteritis and attended accident and emergency department (A&E) around 12 hours later. The husband was alert with normal blood test results at 18 hours following ingestion. Thirty hours later, his total bilirubin increased to 54 μmol/L (reference range, 4-23 μmol/L), serum alanine transaminase (ALT) to 2928 IU/L (reference range, 8-58 IU/L), serum creatinine to 229 μmol/L (reference range, 67-109 μmol/L), and international normalised ratio (INR) to 1.56 (reference level, <1.1). Mushroom poisoning was suspected and the Hong Kong Poison Information Centre was contacted. He was given N-acetylcysteine (NAC), silibinin, and penicillin G in the intensive care unit. Subsequent blood tests showed no improvement and around 48 hours after ingestion, his serum ALT climbed to 4856 IU/L and INR to 2.25. He was transferred to the intensive care unit of Queen Mary Hospital (QMH) for further care. At QMH, computed tomography of the abdomen revealed hypo-enhancement of the liver parenchyma. Liver transplant workup was initiated in view of impending liver failure. Fortunately his liver function started to stabilise 8 hours after admission to QMH, with a serum ALT peak at 3856 IU/L and INR at 3.5. He then made progressive recovery and was discharged 10 days after admission.