Tiffany Wong

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).

Excellent outcomes of liver transplantation using severely steatotic grafts from brain‐dead donors

Liver grafts with macrovesicular steatosis of >60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain‐dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis >60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis >60%), and 354 patients had grafts with ≤60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End‐Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30‐day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1‐year and 3‐year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low‐risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation. Liver Transpl 22:226‐236, 2016.

Prevention of recurrent hepatitis B infection after liver transplantation.

BACKGROUND Recurrence of hepatitis B virus (HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival. The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients. DATA SOURCES Up to January 2013, studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed. RESULTS There have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation, from the discovery of hepatitis B immune globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine. With the development of newer and stronger antiviral agents, the need for life-long HBIG is doubtful. With their low resistance profile, oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome. CONCLUSIONS Restoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.

Hepatobiliary malignancies: lessons from Asia.

With the higher incidences of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in the East compared with the West, Asian centers have made significant contributions to the management of these malignancies. The major risk factor for HCC is hepatitis B infection in Asia in contrast to hepatitis C in Western populations. Barcelona Clinic for Liver Cancer (BCLC) staging that guides the treatment of patients with HCC in the West is considered too conservative by many Asian centers. In Asia, liver resection is widely offered to patients with multifocal, bilobar tumor or tumor invasion to the portal vein. The criteria for liver transplantation for HCC are also often more extended in Asian centers. Asian surgeons pioneered the development of living donor liver transplantation, which plays a major role in the management of early HCC associated with severe cirrhosis in Asia due to shortage of deceased donor graft. Asian centers have also made significant contributions to the modern management of CCA. A more aggressive surgical approach is generally adopted in Asia, including radical lymphadenectomy for intrahepatic CCA and simultaneous hepatic artery and portal vein resection with hepatectomy for hilar CCA. Eastern and Western centers should collaborate in further studies to establish the optimal treatment strategies for hepatobiliary malignancies.

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.

Outcomes of hepatectomy for hepatocellular carcinoma with bile duct tumour thrombus

BACKGROUND Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy. METHODS A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio. RESULTS Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child-Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not. DISCUSSION A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery.

Retransplantation using living-donor right-liver grafts

This study reviews the outcomes of retransplantation using living‐donor right‐liver grafts.

Emerging drugs for prevention of T-cell mediated rejection in liver and kidney transplantation

ABSTRACT Introduction: Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered: In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed. Newer immunosuppressive agents showing promising early data after liver and kidney transplantation will also be explored. Expert Opinion: Currently, calcineurin inhibitors continue to be a vital component of immunosuppressive therapy after solid organ transplantation. Although minimization and avoidance strategies have been developed, the ultimate goal of inducing tolerance remains elusive. Newer emerging agents should have potent and specific immunosuppressive activity, with minimal associated side effects. An individualized approach should be adopted to tailor immunosuppression according to the different needs of recipients.

Impact of intraoperative blood transfusion on long‐term outcomes of liver transplantation for hepatocellular carcinoma

To investigate the impact of intraoperative blood transfusion on the long‐term outcomes of liver transplantation for hepatocellular carcinoma.

Survival outcomes of hepatocellular carcinoma resection with postoperative complications - a propensity-score-matched analysis.

Abstract Curative resection remains the only hope of cure for hepatocellular carcinoma (HCC), but postoperative complications can have a significant impact on long-term survival. However, only scarce data on such impact can be found in the literature. This retrospective study reviewed the prospectively collected data of patients who underwent primary liver resection for HCC at our hospital during the period from December 1989 to December 2014. Patients with and without postoperative complications were compared. A 1:1 propensity score matching was adopted by matching age, comorbidity, Model of End-stage Liver Disease score, tumor stage, and extent of resection. Totally 1710 patients were eligible for the study. Four hundred and sixty-one (27.0%) of them developed postoperative complications while 1249 (73.0%) did not. After propensity score matching, 922 patients were compared in a 1:1 ratio (461 with postoperative complications and 461 without). Patients who developed postoperative complications were demographically similar to patients who did not, but had more intraoperative blood loss and transfusion (both P < 0.001), longer hospital stay (17 vs 9 days; P < 0.001), worse hospital mortality (12.1% vs 0%; P < 0.001), and shorter overall survival (P < 0.001). On multivariate analysis, factors that might have affected overall survival were cancer stage (HR 1.22, P < 0.001), tumor size (HR 1.02, P = 0.005), tumor number (HR 1.08, P < 0.001), venous invasion (HR 1.38, P = 0.003), extent of resection (HR 1.19, P = 0.045), intraoperative blood loss (HR 1.11, P < 0.001), postoperative complication (HR 1.37, P < 0.001), and era effect (HR 1.27, P = 0.01). Patients should be monitored closely after HCC resection. Prompt treatment of postoperative complications may be salvational.