Faisal Saud Dar

Liver transplantation for hepatoblastoma

From October 1993 to February 2007, 25 liver transplantations were performed for hepatoblastoma. Of these 25, 18 children received cadaveric grafts, and 7 received left lateral segments from living donors. Fifteen patients were at level IV in the pretreatment extent of disease staging system for hepatoblastoma (PRETEXT IV; 11 received cadaveric grafts and 4 underwent living related liver transplantation [LRLT]) and 10 were level III (PRETEXT III; 7 received cadaveric grafts and 3 underwent LRLT). Preoperative chemotherapy was given according to the risk stratification system for children with hepatoblastoma protocols of the International Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL): SIOPEL I in the first 3 patients, SIOPEL II in 6, SIOPEL III in 10, and SIOPEL IV in 3 patients. Patient and graft survival after cadaveric transplantation was 91%, 77.6%, and 77.6%, at 1, 5, and 10 years, respectively, with no retransplantations. Patient and graft survival for children undergoing LRLT was 100%, 83.3%, and 83.3%, at 1, 5, and 10 years, respectively. All surviving children but 1 remain disease‐free, with a median follow up of 6.8 years (range, 0.9‐14.9). There were 5 deaths at a median of 13 months post‐transplantation, secondary to tumor recurrence (4) and respiratory failure (1). Liver transplantation is an established treatment for unresectable hepatoblastoma confined to the liver following chemotherapy. LRLT is a therapeutic option given that the outcome is similar to that of resection and cadaveric transplantation. Liver Transpl 14:1614–1619, 2008.

Auxiliary Liver Transplantation for Acute Liver Failure in Children

Objective:The aim of this study is to present the largest experience of auxiliary liver transplantation for acute liver failure (ALF) in children over the past 19 years. Methods:Between 1990 and 2009, a total of 128 liver transplants were performed on children with ALF. Of these, 20 received auxiliary liver transplants (19 were cadaveric and 1 living graft). The recipient median age was 12 years (range: 1 –16). Indications for auxiliary partial orthotopic liver transplantation were seronegative non-A non-B hepatitis in 16 children, drug induced in 2, and 1 autoimmune hepatitis and 1 mushroom poisoning. The median waiting time for transplantation was 2 days (range: 1–9). After native liver partial hepatectomy, 20 grafts were implanted orthotopically and included 8 right lobes, 8 left lateral segments, 3 left lobes, and 1 whole liver. Regeneration of the native liver was assessed by radiologic, nuclear medicine imaging, and histology. Follow-up imaging and biopsies were performed at intervals of 3 to 6 months and yearly. Results:Patient survival was 85% at 1, 5, and 10 years. There were 3 deaths at a median of 9 days (range: 8–52) post-transplantation. There was 1 retransplant for chronic rejection 15 months post-transplantation. There were no biliary or vascular complications. Of 17 survivors, 14 (82%) have successfully regenerated their native liver and so far 11 children (65% of the survivors) have been withdrawn from immunosuppression at a median time of 23 months (range: 4–106) after transplantation. Conclusion:Auxiliary partial orthotopic liver transplantation should be considered in children presenting with ALF who fulfill criteria for liver transplantation.

Outcome of liver transplantation in hereditary hemochromatosis

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism. It is an uncommon indication for liver transplantation (LT). It has been suggested that patients who undergo LT for cirrhosis related to HH have higher morbidity and mortality from cardiac, infectious and malignant complications. The purpose of this retrospective review was to determine whether these observations hold true in the current era. We analysed the data of 22 patients who had LT for HH from 1996 to 2007 at our center. Thirteen patients had LT for complications of end‐stage liver disease, seven for hepatocellular carcinoma (HCC) and two for subacute liver failure. Cofactors promoting liver disease were identified in 15 patients. Ten patients had iron reduction with venesection before transplantation. Patient and graft survival at 1 and 5 years were 80.7%, and 74% respectively. There were seven deaths after a median follow up of 46 months either because of multiorgan failure, or caused by HCC recurrence. Bacterial infections were the commonest cause of morbidity. Patients with HH remain at a higher risk of developing HCC. Infectious complications are common. Iron reduction with preoperative venesection reduces the risk of cardiac and infection complications postoperatively. Improved survival post‐LT reflects changes in selection, disease modification through venesection, and improvement in immunosuppression.

The travails of setting up a living donor liver transplant program: Experience from Pakistan and lessons learned

Living donor liver transplantation (LDLT) is the only treatment option for patients with end‐stage liver disease (ESLD) where cadaveric donors are not available. In developing countries, the inception of LDLT programs remains a challenge. The first successful liver transplantation program in Pakistan started transplantation in 2012. The objective of this study was to report outcomes of 100 LDLT recipients in a developing country and to highlight the challenges encountered by a new LDLT program in a resource‐limited setting. We retrospectively reviewed recipients who underwent LDLT between April 2012 and August 2014. Demographics, etiology, graft characteristics, and operative variables were assessed. Outcome was assessed on the basis of morbidity and mortality. All complications of ≥ 3 on the Clavien‐Dindo grading system were included as morbidity. Estimated 1‐year survival was calculated using Kaplan‐Meier curves, and a Log‐rank test was used to determine the significance. Outcomes between the first 50 LDLTs (group 1) and latter 50 LDLTs (group 2) were also compared. Median age was 46.5 (0.5‐72) years, whereas the median MELD score was 15.5 (7‐37). The male to female ratio was 4:1. ESLD secondary to hepatitis C virus was the most common indication (73% patients). There were 52 (52%) significant (≥ grade 3) complications. The most common morbidities were bile leaks in 9 (9%) and biliary strictures in 14 (14%) patients. Overall mortality in patients who underwent LDLT for ESLD was 10.6%. Estimated 1‐year survival was 87%. Patients who underwent transplantation in the latter period had a significantly lower overall complication rate (36% versus 68%; P = 0.01). Comparable outcomes can be achieved in a new LDLT program in a developing country. Outcomes improve as experience increases. Liver Transpl 21:982‐990, 2015.

Outcome of liver transplantation for haemophilia

BACKGROUND Prior to routine screening of blood products many patients with haemophilia were infected with hepatitis C virus (HCV) and have subsequently gone on to develop end-stage liver disease (ESLD). PATIENTS AND METHODS We report our experience of liver transplantation (LT) in patients with haemophilia that developed ESLD secondary to HCV. Patients transplanted from 1994 to 2008 were identified retrospectively. Patient demographics pre-, intra- and post-operative details and outcome were documented. RESULTS A total of 3800 LT were performed of which 13 had haemophilia A, 4 haemophilia B and one factor (F)X deficiency. All patients were male with a median age of 52 years (range 26-59), all were HCV antibody positive, 5 (28%) were human immunodeficiency virus (HIV) positive and 4 (22%) had hepatocellular carcinoma. Median intra-operative blood loss was 4.2 l (range 0.8-12) and all received coagulation factor support peri-operatively. Coagulation was unsupported by 72 h post-operatively in all recipients. Two patients developed complications as a result of post-operative bleeding. At a median follow-up of 90 months, 8 patients have died, including 4 of the 5 patients that were HIV positive. The median survival of patients with and without HIV co-infection was 26 and 118 months, respectively. CONCLUSION LT in patients with haemophilia cures the coagulation disorder and in the absence of HIV/HCV co-infection is associated with long-term patient survival.

Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level.

Reversal of acquired hepatocerebral degeneration with living donor liver transplantation

Many patients with cirrhosis eventually develop complications of end-stage liver disease (ESLD). Deposition of toxins, eg, ammonia in the brain, results in hepatic encephalopathy (HE). In a subset of patients, there is a chronic form of non-Wilsonian encephalopathy called acquired hepatocerebral degeneration (AHD). The pathogenesis of AHD is thought to be due to an accumulation of manganese (Mn) in the brain, which can be seen as hyperintensities of globus pallidus (GP), lenticular nucleus, and substantia nigra on T1-weighted sequences of brain magnetic resonance imaging (MRI) scans. Clinically, AHD is characterized by extrapyramidal and neuropsychiatric symptoms, including delirium, apathy, lethargy, somnolence, emotional instability, and movement disorders, such as tremor, parkinsonism, akinesia, choreoathetosis, myoclonus, ataxia, asterixis, dystonia, pyramidal signs, and myelopathy. No medical treatment has been reported to reverse the progression of AHD. Before the advent of liver transplant, HE was considered reversible with the only exception of the AHD cases, which were labeled refractory to optimal available treatment. Recent studies suggest that liver transplant may be an effective therapy for AHD. In Pakistan, only 1 case report has been published on AHD. Shifa International Hospital, being the only liver transplantation center in the country, offers a needed platform to test this hypothesis. Herein, we describe findings of a retrospective study done to determine the radiological and clinical reversibility of AHD in chronic liver disease (CLD) patients treated with living donor liver transplantation (LDLT) or optimal medical treatment. The study was approved by the hospital ethics committee and funded by the Neurology Department Education and Research Fund. We reviewed a database of 531 patients diagnosed with CLD in the inpatient records of the gastroenterology and hepatology department of Shifa International Hospital. Data were extracted via an electronic timeline search from January 1, 2013 to December 31, 2013 using keywords “CLD,” “chronic liver disease,” “endstage liver disease,” and/or “cirrhosis.” A similar search was run in the radiology department of the hospital to screen patients who underwent a brain MRI. Sixty-three out of the 531 patients underwent MRI brain scans. We searched for patients with confirmed AHD in their diagnosis. Patients were filtered and selected on the basis of our set of inclusion and exclusion criteria: inclusion criteria—patients with CLD and AHD who underwent brain MRI from January 1, 2013 to December 31, 2013; exclusion criteria—patients with CLD but with other central nervous system findings on MRIs, ie, cerebrovascular accident (CVA), infectious diseases, space-occupying lesions (SOLs), or Wilson’s disease. Decompensated liver disease was documented by reviewing results from patients’ medical records. The severity of the liver disease was assessed by ChildTurcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores. Pretransplant and posttransplant signs and symptoms were separately listed. The motor impairment severity (MIS) index was used to assess the presence and severity (0, absent; 1, mild; 2, moderate; 3, severe; 4, extremely severe) of the following motor signs: bradykinesia, tremor, dystonia, dyskinesia, dysarthria, and ataxia. The graded

Liver transplantation for syndromic biliary atresia with a pedunculated accessory hepatic lobe

Faraj W, Dar F, Marangoni G, Alvarez FE, Howlader M, Mukherji D, Heaton N, Rela M. Liver transplantation for syndromic biliary atresia with a pedunculated accessory hepatic lobe.
Pediatr Transplantation 2010: 14: E1–E3.

Predictors of early graft survival after pediatric liver transplantation

The objective of this study was to identify peritransplant predictors of early graft survival and posttransplant parameters that could be used to predict early graft outcomes after pediatric liver transplantation (PLT). The response of children to liver dysfunction after liver transplantation (LT) is poor. No data have been reported for early predictors of poor graft survival, which would potentially be valuable for rescuing children at risk after LT. A retrospective cohort study of 422 PLT procedures performed from 2000 to 2010 at a single center was conducted. Multiple peritransplant variables were analyzed. Univariate and multivariate analyses using receiver operating characteristic curves were performed to identify predictors of early graft loss (ie, at 30, 60, and 90 days). The number needed to treat (NNT) was calculated when the risk factors were identified. Comparisons with the Olthoff criteria for early graft dysfunction in adults were performed. The overall 30‐, 60‐, and 90‐day graft survival rates were 93.6%, 92.6%, and 90.7%, respectively. A recipient age of 0 to 2 or 6 to 16 years, acute liver failure, and a posttransplant day 7 serum bilirubin level > 200 μmol/L were risk factors for graft loss in the 3‐strata Cox models. The product of the peak aspartate aminotransferase (AST) level, day 2 international normalized ratio (INR) value, and day 7 bilirubin level [with 30‐, 60‐, and 90‐day areas under the receiver operating characteristic curve (AUROCs) of 0.774, 0.752, and 0.715, respectively] and a day 7 bilirubin level > 200 μmol/L (with 30‐, 60‐, and 90‐day AUROCs of 0.754, 0.661, and 0.635, respectively) provided excellent prediction rates for early graft loss (30‐days for Day‐7‐bilirubin level > 200) in the pediatric population (sensitivity = 72.7%, specificity = 96.6%, positive predictive value = 95.5%, negative predictive value = 78%). The NNT with early retransplantation when the day 7 bilirubin level was >200 μmol/L was 2.17 (unadjusted) or 2.76 (adjusted for graft survival). In conclusion, 2 scores—the product of the peak AST level, day 2 INR value, and day 7 bilirubin level and a posttransplant day 7 bilirubin level > 200 μmol/L—have been identified as clinically valuable tools with high accuracy for predicting early graft loss. A more aggressive attitude to considering early retransplantation in this group may further improve survival after LT. Liver Transpl 18:1324–1332, 2012.

Liver transplantation from a non-heart-beating donor after pulmonary failure: Report of a case

We report a case of successful liver transplantation after controlled donor after cardiac death procurement from a donor who died of pulmonary failure. The donor was a 28-year-old woman with idiopathic pulmonary fibrosis, whose life support could not continue when her condition deteriorated rapidly while waiting for a suitable donor for lung transplantation. She was on noninvasive negative pressure ventilatory support before the donor organs were procured.