Mohammed Al Sebayel

Liver transplantation for hepatitis B virus: Decreasing indication and changing trends

AIM To evaluate the indication and outcome of hepatitis B virus (HBV)-related liver transplantation (LT) in the era of newer antiviral agents. METHODS We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center. These data included demographic, perioperative and long-term postoperative follow-up data including viral serological markers, HBV DNA, and repeated liver imaging. Between January 1990 and January 2012, 133 patients (106 males and 27 females) underwent LT for HBV-related cirrhosis at our center. All patients were followed up frequently during the first year following transplantation, according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter. Breakthrough infection was defined as re-emergence of HBV-DNA or hepatitis B surface antigen (HBsAg) while on treatment. Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HBIG and at least one nucleos(t)ide analog. RESULTS One hundred and thirty-three patients underwent LT for HBV and were followed for a median of 82 mo (range: 1-274). The rates of post-LT survival and HBV recurrence during the follow-up period were 89% and 11%, respectively. The following factors were associated with disease recurrence: younger age (44.3 ± 16.2 years vs 51.4 ± 9.9 years, P = 0.02), positive pretransplant hepatitis B e antigen (HBeAg) (60% vs 14%, P < 0.0001), detectable pretransplant HBV DNA (60% vs 27%, P = 0.03), positive posttransplant HBsAg (80% vs 4%, P < 0.0001) and positive posttransplant HBeAg (27% vs 1%, P < 0.0001). Forty-four (33%) patients had hepatocellular carcinoma (HCC). In the first (pre-2007) group, HBV was the second leading indication for LT after hepatitis C virus infection. A total of 64 transplants were performed, including 46 (72%) for decompensated HBV cirrhosis, 12 (19%) for decompensated cirrhosis complicated by HCC and 6 (10%) for compensated cirrhosis complicated by HCC. In the second group, nonalcoholic steatohepatitis surpassed HBV as the second leading indication for LT. A total of 69 HBV related transplants were performed, including 43 (62%) for decompensated HBV cirrhosis, 7 (10%) for decompensated cirrhosis complicated by HCC and 19 (27.5%) for compensated cirrhosis complicated by HCC. There was a significant (P = 0.007) increase in the number of transplants for compensated cirrhosis complicated by HCC. CONCLUSION The use of potent anti-HBV agents has led to a changing trend in the indications for LT. HBV is currently the third leading indication for LT in this hyperendemic area.

Liver transplantation in Wilson’s disease: Single center experience from Saudi Arabia

AIM To determine liver transplantation outcomes in Wilsons disease (WD) patients, focusing on neurological manifestations. METHODS This retrospective study assessed data from 16 WD patients (nine males, 56%) who had liver transplants between 1991 and 2007. Survival, graft function, and neurological complications were assessed during a follow-up period of up to 15 years. In addition, each patients medical record was reviewed in detail to find the type of Wilsons disease (hepatic or hepatic plus neurological WD), indication for liver transplantation, use of chelating agents prior to transplantation, immediate and long term complications following transplantation, the donor details, and the pathology of explanted liver. RESULTS End-stage liver disease was the indication for transplantation in all 16 WD patients. Four patients displayed WD-related neurological symptoms in addition to liver disease. Living-related liver transplantation was done in three cases. One patient died on postoperative day 6 due to primary graft non-function. One-year post liver transplant survival was 94%. Neurological manifestations of all four patients disappeared during their follow-up. Four patients developed acute cellular rejection, but all responded to treatment. One patient developed chronic ductopenic rejection after 15 years post-transplantation and their graft failed; this patient is currently waiting for re-transplantation. Fourteen patients (88%) are still living. The long-term average survival is currently 10.5 years, with a current median survival of 8 years. Long-term graft survival is currently 81%. CONCLUSION Short- and long-term survival in WD patient liver transplantation was excellent, and neurological and psychological WD manifestations disappeared during long-term follow-up.

Day-of-surgery rejection of donors in living donor liver transplantation

AIM To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT). METHODS This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donors serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholangiopancreatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation. RESULTS Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, narcotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras, open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparoscopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results. CONCLUSION The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.

Coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma (collision tumors) after liver transplantation: a case report.

Coincidental occurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma, known as “collision tumors”, within a cirrhotic liver is rare. Herein, we report a case of liver transplantation (LT) in a patient with such collision tumors. Our patient was a 56-year-old woman with hepatitis C virus-related cirrhosis and 2 focal hepatic lesions, measuring 1.5 and 3 cm, in the liver segments 8 and 5, respectively. The lesion on segment 8 showed the typical radiological characteristics of HCC; however, the lesion in segment 5 showed an atypical vascular pattern and was closely associated with the inferior vena cava. Serum alpha-fetoprotein level was normal and serum carbohydrate antigen 19-9 (CA19-9) level was slightly elevated (63 U/mL); the extrahepatic spread of HCC was ruled out. The patient underwent an uneventful deceased-donor LT. Histopathological examination of the explant confirmed that the lesion on segment 8 was an HCC, but surprisingly, the lesion on segment 5 was found to be a cholangiocarcinoma. Six months after LT, the serum CA19-9 level was markedly elevated (255 U/mL), and the patient began experiencing abdominal pain. Magnetic resonance imaging showed enlarged hilar and paraaortic lymph nodes that were suggestive of metastases; histopathological analysis using ultrasound (US)-guided biopsy confirmed recurrent cholangiocarcinoma. Unfortunately, the patient died because of tumor recurrence 9 months after LT. Collision tumor resulting from the co-existence HCC and cholangiocarcinoma in a cirrhotic liver is rare and has a negative impact on the outcome of LT. Atypical vascular pattern and elevated serum CA19-9 levels are suggestive of such tumors; patients with these findings should undergo a targeted biopsy to rule out the coincidental occurrence of HCC and cholangiocarcinoma.

Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting

Background Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. Methods This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. Results A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. Conclusions LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.

Liver transplantation in the Kingdom of Saudi Arabia

The first liver transplantation (LT) in Saudi Arabia was performed in 1991; however, it was not until 1994 that the first structured LT program was launched. Until 1997, all LTs in the Kingdom of Saudi Arabia (KSA) were deceased donor liver transplantations. Programs performing LTs needed the authorization of the Saudi Center for Organ Transplantation (SCOT), which provides the essential support for organ procurement and allocation as well as regulatory support for organ transplantation in the country. Currently, there are 4 LT centers in the KSA. Three centers are in Riyadh, the capital city of KSA, and 1 is in the city of Dammam in the Eastern province. Pediatric living donor liver transplantation (LDLT) began in 1997, while the adult LDLT program started 4 years later in 2001. Currently, more than 2000 LTs have been performed by the 4 centers in the KSA. Over 50% of those were performed at King Faisal Specialist Hospital and Research Center in Riyadh. The outcomes of these transplants have been comparable with the international standards. The aim of this review is to provide an overview of LT in KSA. Liver Transplantation 23 1312–1317 2017 AASLD.

Surgical management of biliary complications following living donor liver transplantation.

Khalaf H, Alawi K, Alsuhaibani H, Hegab B, Kamel Y, Azzam A, Albahili H, Alsofayan M, Al Sebayel M. Surgical management of biliary complications following living donor liver transplantation.
Clin Transplant 2011: 25: 504–510.

Utility of post-liver transplantation Meld and delta Meld in predicting early and late mortality

Introduction The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (&Dgr;MELD) in predicting the mortality after LT is still controversial. Aim The aim of this study was to assess the ability of absolute and &Dgr;MELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. Patients and methods Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. Results One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and &Dgr;MELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14–1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14–1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. Conclusion Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.

Aggressive recurrence of primary hepatic epithelioid hemangioendothelioma after liver transplantation.

HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.