Publications by authors named "Bandar Al-Judaibi"

40 Publications

Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

Biomed Pharmacother 2021 Nov 22;143:112195. Epub 2021 Sep 22.

Department of Medical Genetics, University of British Columbia, Vancouver, Canada; BC Children's Hospital Research Institute, Vancouver, Canada; Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, Canada; Pharmaceutical Outcomes Program, British Columbia Children's Hospital, Vancouver, Canada. Electronic address:

Background: The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia.

Methods: We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants.

Results: We identified a novel association in the gene coding glycophorin C (rs6741425; OR:0.12, 95%CI:0.04-0.34, P = 2.94 × 10) that predicts protection against ribavirin-induced anemia. We also replicated the associations of ITPA and VDR genetic variants with the development of ribavirin-induced anemia (rs1127354; OR:0.13, 95%CI:0.04-0.41, P = 8.66 ×10; and rs1544410; OR:1.65, 95%CI:1.01-2.70, P = 0.0437).

Conclusions: GYPC variation affecting erythrocyte membrane strength is important in predicting risk for developing ribavirin-induced anemia. ITPA and VDR genetic variants are also important predictors of this adverse reaction.
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http://dx.doi.org/10.1016/j.biopha.2021.112195DOI Listing
November 2021

Use of COVID-19 vaccines in patients with liver disease and post-liver transplantation: Position statement of the Saudi association for the study of liver diseases and transplantation.

Saudi J Gastroenterol 2021 Jul-Aug;27(4):201-207

College of Medicine, Alfaisal University, Riyadh; Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Patients with chronic liver disease (CLD) and liver transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). Although several studies demonstrated the safety and efficacy of COVID-19 vaccines in the general population, data in CLD patients and liver transplant recipients are lacking. Two COVID-19 vaccines were approved by the Saudi Food and Drug Authority and rolled out to several million recipients in Saudi Arabia. These vaccines are mRNA-based vaccine BNT162b2 from Pfizer/BioNTech and adenovirus-based AZD1222 from Oxford/AstraZeneca from three manufacturing sites (EU Nodes, Serum Institute of India, and South Korea Bio). The Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has reviewed the available evidence and issued interim recommendations for COVID-19 vaccination in CLD and liver transplant recipients. Since there is no evidence contradicting the safety and immunogenicity of the currently approved COVID-19 vaccines in patients with CLD and hepatobiliary cancer and liver transplant recipients, the SASLT recommends vaccination in those patient populations. CLD and hepatobiliary cancer patients and liver transplant recipients should be prioritized depending on the risk factors for severe COVID-19. In transplant recipients, the optimal timing of vaccination remains unknown; however, immunization is recommended after the initial immunosuppression phase. Patients with CLD and liver transplant candidates or recipients should be closely monitored after COVID-19 vaccination. These patient populations should be included in future clinical trials to provide further evidence on the efficacy and safety of COVID-19 vaccines.
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http://dx.doi.org/10.4103/sjg.sjg_223_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448010PMC
September 2021

Barriers to research productivity among physicians in Saudi Arabia: Taking a deep dive into the world of academia.

Saudi J Gastroenterol 2021 Mar-Apr;27(2):61-63

Division of Transplantation, University of Rochester, Rochester, New York, United States of America.

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http://dx.doi.org/10.4103/sjg.sjg_7_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183357PMC
May 2021

Estimating the effect of increasing utilization of living donor liver transplantation using observational data.

Transpl Int 2021 04 26;34(4):648-656. Epub 2021 Feb 26.

Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, Rochester, NY, USA.

There has been a recent increase in enthusiasm for expansion of living donor liver transplantation (LDLT) programmes. Using all adults initially placed on the waiting list in the United States, we estimated the risk of overall mortality under national strategies which differed in their utilization of LDLT. We used a generalization of inverse probability weighting which can estimate the effect of interventions in the setting of finite resources. From 2005 to 2015, 93 812 eligible individuals were added to the waitlist: 51 322 received deceased donor grafts while 1970 underwent LDLT. Individuals who underwent LDLT had more favourable prognostic factors, including lower mean MELD score at transplant (14.6 vs. 20.5). The 1-year, 5-year and 10-year cumulative incidence of death under the current level of LDLT utilization were 18.0% (95% CI: 17.8, 18.3%), 41.2% (95% CI: 40.8, 41.5%) and 57.4% (95% CI: 56.9, 57.9%) compared to 17.9% (95% CI: 17.7, 18.2%), 40.6% (95% CI: 40.2, 40.9%) and 56.4% (95% CI: 55.8, 56.9%) under a strategy which doubles LDLT utilization. Expansion of LDLT utilization would have a measurable, modest effect on the risk of mortality for the entire cohort of individuals who begin on the transplant waiting list.
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http://dx.doi.org/10.1111/tri.13835DOI Listing
April 2021

Cholestasis and disseminated histoplasmosis in a psoriatic patient on infliximab: case report and review of literature.

BMC Gastroenterol 2020 May 8;20(1):141. Epub 2020 May 8.

Division of Gastroenterology and Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 646, Rochester, NY, 14642, USA.

Background: Histoplasma capsulatum is the most common endemic mycosis in the United States and frequently presents as an opportunistic infection in immunocompromised hosts. Though liver involvement is common in disseminated histoplasmosis, primary gastrointestinal histoplasmosis of the liver in absence of lung involvement is rare. Similarly, cholestatic granulomatous hepatitis in liver histoplasmosis is rarely seen.

Case Presentation: We present a rare case of primary gastrointestinal histoplasmosis manifesting with acute granulomatous hepatitis and cholestasis in a 48-year-old female with psoriatic arthritis, receiving methotrexate and infliximab. The epidemiology, risk factors, clinical presentation, diagnosis, and treatment of histoplasmosis is discussed. Furthermore, we review the published cases of biopsy-proven disseminated histoplasmosis with cholestatic jaundice to highlight histoplasmosis involvement in the liver.

Conclusion: Histoplasmosis should be considered in immunosuppressed patients with fever, chills, abdominal pain and cholestasis with progressive jaundice, particularly in subjects without evidence of biliary obstruction. Future studies are needed to accurately assess the risk of this fungal infection, specifically in patients on immunomodulatory therapy for autoimmune disease.
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http://dx.doi.org/10.1186/s12876-020-01290-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206703PMC
May 2020

Gastrointestinal and liver manifestations of COVID-19.

Saudi J Gastroenterol 2020 Sep-Oct;26(5):226-232

Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, United Sates of America.

The novel coronavirus 2 (SARS-CoV-2) has spread worldwide. While patients typically present with fever and symptoms of a respiratory illness, patients have also presented with gastrointestinal symptoms such as diarrhea, vomiting and abdominal pain. In addition, some patients were reported to have liver injury. In this article, we review gastrointestinal and liver aspects of COVID-19. In addition, we provide general gastroenterologists with guidance on the management of patients with gastrointestinal and liver disorders from COVID-19.
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http://dx.doi.org/10.4103/sjg.SJG_147_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739995PMC
October 2020

Saudi association for the study of liver diseases and transplantation position statement on liver transplantation during the COVID-19 pandemic.

Saudi J Gastroenterol 2020 Sep-Oct;26(5):233-239

Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia.

The World Health Organization (WHO), on March 11 2020, upgraded the status of the novel coronavirus disease (COVID-19) from epidemic to pandemic. Over two million individuals have been infected with SARS-CoV-2, the virus causing COVID-19, and as of April, 14 2020, there were over 5000 confirmed cases in Saudi Arabia (SA). Many countries, including SA, have imposed major restrictions on travel, and everyday life, and the implications of these necessary changes are being felt in liver transplant (LT) centers in SA. Concerns remain that there is an increased risk for individuals over 65 years of age, with underlying medical conditions, or for those who are immunocompromised. Therefore, the Saudi Association for the Study of Liver Diseases and Transplantation (SASLT) established an urgent task force to launch a statement that can be utilized by LT centers as a guidance in the management of patients with advanced liver disease from the time of LT listing to the post-operative care of transplanted patients.
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http://dx.doi.org/10.4103/sjg.SJG_131_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739988PMC
October 2020

Exercise Training for Liver Transplant Candidates.

Transplant Proc 2019 Dec 13;51(10):3330-3337. Epub 2019 Nov 13.

Department of Medicine, Division of Gastroenterology, Western University and London Health Sciences Centre, London, Ontario, Canada; Multi-Organ Transplant Program, Western University and London Health Sciences Centre, London, Ontario, Canada.

Background And Aims: Frailty is associated with increased morbidity and mortality, and this is tightly linked to liver decompensation and increased complication rates among liver transplant (LT) candidates. The aim of the study was to evaluate the efficacy of a structured in- and outpatient exercise training program for cirrhotic patients who were referred for liver transplant evaluation.

Methods: We retrospectively reviewed 458 consecutive LT patients. There were 200 patients who underwent LT prior to the implementation of an exercise training program (non-ETP) and 258 LT patients who underwent a comprehensive exercise training program (ETP). Baseline characteristics, readmission rate, and length of hospital stay (LOS) were analyzed and compared between the 2 groups.

Results: The ETP group were more likely to have diabetes mellitus and coronary artery disease. However, there was no significant difference in the postoperative complication rates between the 2 groups except for more infections in the ETP group compared to the non-ETP group. There was a trend toward lower 90-day readmission rate in the ETP group (17.9% vs 20%) and shorter LOS (14 vs 17 days).

Conclusion: There was a trend toward reduced 90-day readmission and shorter length of stay after implementation of an exercise training program.
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http://dx.doi.org/10.1016/j.transproceed.2019.08.045DOI Listing
December 2019

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials.

Intensive Care Med 2020 01 7;46(1):1-16. Epub 2019 Oct 7.

Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Purpose: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure.

Methods: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.

Results: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain.

Conclusions: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.
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http://dx.doi.org/10.1007/s00134-019-05783-yDOI Listing
January 2020

Position statement on the diagnosis and management of non-alcoholic fatty liver disease.

Saudi Med J 2019 Jun;40(6):531-540

Department of Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.
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http://dx.doi.org/10.15537/smj.2019.6.23980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778754PMC
June 2019

The role of imaging in determining prognosis for primary sclerosing cholangitis: A systematic review.

Saudi J Gastroenterol 2019 May-Jun;25(3):152-158

Department of Medicine, University of Rochester, Rochester, New York, USA.

Background/aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression.

Materials And Methods: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS).

Results: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression.

Conclusion: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.
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http://dx.doi.org/10.4103/sjg.SJG_478_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526736PMC
April 2020

Surgical resection vs radiofrequency ablation in older adults with early stage hepatocellular carcinoma: Where do we stand?

Saudi J Gastroenterol 2018 Nov-Dec;24(6):309-310

Division of Transplantation, University of Rochester, Rochester, New York, United States of America.

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http://dx.doi.org/10.4103/sjg.SJG_501_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253914PMC
December 2018

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Can J Surg 2019 02;62(1):44-51

From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro).

Background: Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre.

Methods: We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate.

Results: Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era.

Conclusion: We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.
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http://dx.doi.org/10.503/cjs.012017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351268PMC
February 2019

The Effect of the Opioid Epidemic on Donation After Circulatory Death Transplantation Outcomes.

Transplantation 2019 05;103(5):973-979

Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, Rochester, NY.

Background: The opioid epidemic and the deaths of otherwise healthy individuals due to drug overdose in the United States has major implications for transplantation. The current extent and safety of utilization of liver and kidney grafts from donation after circulatory death (DCD) donors who died from opioid overdose is unknown.

Methods: Using national data from 2006 to 2016, we estimated the cumulative incidence of graft failure for recipients of DCD grafts, comparing the risk among recipients of organs from donors who died of anoxic drug overdose and recipients of organs from donors who died of other causes.

Results: One hundred seventy-nine (6.2%) of 2908 liver graft recipients and 944 (6.1%) of 15520 kidney graft recipients received grafts from donors who died of anoxic drug overdose. Grafts from anoxic drug overdose donors were less frequently used compared with other DCD grafts (liver, 25.9% versus 29.6%; 95% confidence interval [CI] for difference, -6.7% to -0.7%; kidney, 81.0% versus 84.7%; 95% CI for difference, -7.3% to -0.1%). However, the risk of graft failure at 5 years was similar for recipients of anoxic drug overdose donor grafts and recipients of other grafts (liver risk difference, 1.8%; 95% CI, -7.8% to 11.8%; kidney risk difference, -1.5%; 95% CI, -5.4% to 3.1%).

Conclusions: In the context of the current opioid epidemic, utilization of anoxic drug overdose DCD donor grafts does not increase the risk of graft failure and may help to address waitlist demands.
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http://dx.doi.org/10.1097/TP.0000000000002467DOI Listing
May 2019

Exercise in cirrhosis: Translating evidence and experience to practice.

J Hepatol 2018 11 30;69(5):1164-1177. Epub 2018 Jun 30.

Physical Therapy, Faculty of Rehabilitation, University of Alberta, Edmonton, AB, Canada.

Physical inactivity, sarcopenia, and frailty are highly prevalent, independent predictors of morbidity and mortality in patients with cirrhosis. Across a range of chronic diseases, exercise training is a key recommendation supported by guidelines and, for some conditions, even by governmental funding of exercise programmes. Consistent with the broader chronic disease literature, the evidence for a benefit of exercise in cirrhosis is promising. Several small trials have reported significant improvements in muscle health (mass, strength, functional capacity), quality of life, fatigue, and reductions in the hepatic venous pressure gradient, without adverse events. With strong emerging evidence surrounding the substantial risks of sarcopenia/frailty and our first-hand experiences with liver pre-transplant exercise programmes, we contend that routine patient care in cirrhosis should include an exercise prescription. Some clinicians may lack the resources and necessary background to translate the existing evidence into a practicable intervention. Our team, comprised of physiotherapists, exercise physiologists, hepatologists, transplant specialists, and knowledge translation experts from six North American centres, has distilled the essential background information, tools, and practices into a set of information ready for immediate implementation into clinics ranging from a family practice setting to specialty cirrhosis clinics. Augmenting the rationale and evidence are supplementary materials including video and downloadable materials for both patients and the physician. Supporting the exercising patient is a section regarding information about nutrition, providing practical tips suitable for all patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2018.06.017DOI Listing
November 2018

Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience.

Ann Hepatol 2018 May-June;17(3):437-443. Epub 2018 Apr 9.

Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada.

Introduction And Aim: Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status.

Material And Methods: A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status.

Results: 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported.

Conclusions: SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list .
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http://dx.doi.org/10.5604/01.3001.0011.7388DOI Listing
May 2019

Apixaban and Rosuvas--tatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease.

Drug Metab Dispos 2018 05 22;46(5):485-492. Epub 2018 Feb 22.

Department of Physiology and Pharmacology (R.G.T., C.Z., U.I.S, R.B.K.), Division of Clinical Pharmacology, Department of Medicine (R.G.T., C.Z., M.L., U.I.S., R.B.K.), Department of Medical Imaging (Z.K.), Division of Gastroenterology, Department of Medicine (B.A.-J., M.D.B.), and Lawson Health Research Institute (R.G.T., Z.K., R.S., M.R., U.I.S., R.B.K., M.D.B.), University of Western Ontario, London, Ontario, Canada; and Department of Medicine, University of Rochester, Rochester, New York (B.A.-J.)

There is little known about the impact of nonalcoholic fatty liver disease (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously in subjects with magnetic resonance imaging-confirmed NAFLD ( = 22) and healthy control subjects ( = 12). The area under the concentration-time curve to the last sampling time (AUC) values for apixaban were not different between control and NAFLD subjects (671 and 545 ng/ml × hour, respectively; = 0.15). Similarly, the AUC values for rosuvastatin did not differ between the control and NAFLD groups (25.4 and 20.1 ng/ml × hour, respectively; = 0.28). Furthermore, hepatic fibrosis in NAFLD subjects was not associated with differences in apixaban or rosuvastatin pharmacokinetics. Decreased systemic exposures for both apixaban and rosuvastatin were associated with increased body weight ( < 0.001 and < 0.05, respectively). In multivariable linear regression analyses, only participant weight but not NAFLD, age, or // genotypes, was associated with apixaban and rosuvastatin AUC ( < 0.001 and = 0.06, respectively). NAFLD does not appear to affect the pharmacokinetics of apixaban or rosuvastatin.
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http://dx.doi.org/10.1124/dmd.117.079624DOI Listing
May 2018

Optimizing associated liver partition and portal vein ligation for staged hepatectomy outcomes: Surgical experience or appropriate patient selection?

Can J Surg 2017 Dec;60(6):408-415

From the Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ont. (Al Hasan, Tun-Abraham, Garcia-Ochoa, Hernandez-Alejandro); the Department of Surgery, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Al-Judaibi); the Division of Transplantation, University of Rochester Medical Center, Rochester, Minn. (Levstik); and the Department of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia (Al-Judaibi).

Background: Early reports of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) outcomes have been suboptimal. The literature has confirmed that learning curves influence surgical outcomes. We have 54 months of continuous experience performing ALPPS with strict selection criteria. This study aimed to evaluate the impact of the learning curve on ALPPS outcomes.

Methods: We retrospectively compared patients who underwent ALPPS between April 2012 and March 2016. Patients were grouped into 2 24-month (early and late) periods. All candidates had a high tumour load requiring staged hepatectomy after chemotherapy response, a predicted future liver remnant (FLR) less than 30% and good performance status.

Results: Thirty-three patients underwent ALPPS during the study period: 16 in the early group (median age 65 yr, mean body mass index [BMI] 27) and 17 in the late group (median age 60 yr, mean BMI 25). Bilobar disease was comparable in both groups (94% v. 88%, > 0.99). Duration of surgery was not statistically different. Intraoperative blood loss and need for transfusion were significantly lower in the late group (200 ± 109 mL v. 100 ± 43 mL, < 0.05). The late group had a higher proportion of monosegment ALPPS (4:1). There were no deaths within 90 days in either cohort. Rates of postoperative complications were not statistically significant between groups. The R0 resection rate was similar. The entire 1-year disease-free and overall survival were 52% and 84%, respectively.

Conclusion: Excellent results can be obtained in innovative complex surgery with careful patient selection and good technical skills. Additionally, the learning curve brought confidence to perform more complex procedures while maintaining good outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726970PMC
http://dx.doi.org/10.1503/cjs.005817DOI Listing
December 2017

Tobacco Use is a Modifiable Risk Factor for Post-Transplant Biliary Complications.

J Gastrointest Surg 2017 Oct 7;21(10):1643-1649. Epub 2017 Aug 7.

Division of Solid Organ Transplantation, Department of Surgery, University of Rochester Medical Center, 601 Elmwood Ave, Box SURG - TRANSPLANT, Rochester, NY, 14642, USA.

Purpose: Biliary complications following liver transplantation are a significant source of morbidity, potentially leading to graft failure necessitating retransplantation. We sought to evaluate smoking as an independent risk factor for post-transplant biliary complications.

Methods: The clinical course of all adult primary deceased donor liver transplants at our center from 1992 to 2012 was reviewed. Eligible patients were assigned to cohorts based on their lifetime tobacco exposure: never smokers indicating 0 pack-year exposure and all others were ever smokers. Biliary complications were defined as strictures, leaks, or bilomas requiring intervention. Complication rates were analyzed using univariate regression models correlated with donor and recipient characteristics. Associations found during univariate analysis were included in the final multivariate Cox model.

Results: Eight hundred sixty-five subjects were followed for a median of 65 months; 482 (55.7%) of patients had a positive smoking history at the time of transplant. In univariate analysis, positive tobacco smoking history (HR = 1.36; p = 0.037) and increased time from quit date to transplantation (HR = 0.998; p = 0.011) were positive and negative predictors of biliary complication, respectively. Lifetime tobacco exposure remained a significant predictor of biliary complication on multivariate analysis (HR = 1.408; p = 0.023).

Conclusions: Smoking status is an independent predictor of post-transplant biliary complications, and the data presented reinforces the importance of early smoking cessation in the pre-transplantation period.
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http://dx.doi.org/10.1007/s11605-017-3519-6DOI Listing
October 2017

Clinical Impact of Portal Vein Thrombosis Prior to Liver Transplantation: A Retrospective Cohort Study.

Ann Hepatol 2017 March-April;16(2):236-436

Division of Surgery (Transplantation), University of Alberta, Edmonton, Canada.

Introduction: To identify the impact of portal vein thrombosis (PVT) and associated medical and surgical factors on outcomes post liver transplant (LT).

Material And Methods: Two analyses were performed. Analysis One: cohort study of 505 consecutive patients who underwent LT (Alberta) between 01/2002-12/2012. PVT was identified in 61 (14%) patients. Analysis Two: cohort study of 144 consecutive PVT patients from two sites (Alberta and London) during the same period. Cox multivariable survival analysis was used to identify independent associations with post-LT mortality.

Results: In Analysis One (Alberta), PVT was not associated with post-LT mortality (log rank p = 0.99). On adjusted analysis, complete/occlusive PVT was associated with increased mortality (Hazard Ratio (HR) 8.4, p &lt; 0.001). In Analysis Two (Alberta and London), complete/occlusive PVT was associated with increased mortality only on unadjusted analysis (HR 3.7, p = 0.02). On adjusted analysis, Hepatitis C (HR 2.1, p = 0.03) and post-LT portal vein re-occlusion (HR 3.2, p = 0.01) were independently associated with increased mortality.

Conclusion: Well-selected LT patients who had PVT prior to LT had similar post-LT outcomes to non-PVT LT recipients. Subgroups of PVT patients who did worse post-LT (complete/occlusive thrombosis pre-LT, Hepatitis C or post-LT portal vein re-occlusion) warrant closer evaluation in listing and management post-LT.
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http://dx.doi.org/10.5604/16652681.1231582DOI Listing
April 2017

Building a hepatitis C virus treatment strategy to achieve the 2030 vision for Saudi Arabia.

Saudi J Gastroenterol 2017 Jan-Feb;23(1):71

Division of Gastroenterology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia; Division of Gastroenterology, Department of Medicine, University of Rochester, United States of America; Division of Gastroenterology, Department of Medicine, Western University, Canada.

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http://dx.doi.org/10.4103/1319-3767.199119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329981PMC
June 2017

Is vitamin e or ursodeoxycholic acid a valid treatment option for nonalcoholic fatty liver disease in 2016?

Saudi J Gastroenterol 2016 May-Jun;22(3):169-70

Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; Department of Medicine, King Saud University, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.4103/1319-3767.182462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898083PMC
December 2016

The new era of hepatitis C virus therapy.

Saudi J Gastroenterol 2015 Nov-Dec;21(6):345-54

Department of Medicine, Multi-Organ Transplant Unit, Western University, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia, .

The hepatitis C virus (HCV) has a significant medical and economic impact on societies around the world, and it has been estimated that 130-180 million people are infected with HCV. Therapies for HCV are currently undergoing a revolution. In recent years, several new treatments have been approved by the United States Food and Drug Administration, and many other treatments are in phase II or III clinical trials, including direct antiviral agents (DAAs). Due to recent major advances in the field of HCV therapy, a summary of findings on new HCV therapies are provided in this review article, including reports on new DAAs.
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http://dx.doi.org/10.4103/1319-3767.170947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707801PMC
October 2016

Ribavirin-free treatment may soon be a reality.

Saudi J Gastroenterol 2015 Jul-Aug;21(4):260-1

Department of Medicine, Multi-Organ Transplant Unit, Western University, London, Ontario, Canada; Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia, .

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http://dx.doi.org/10.4103/1319-3767.161633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542427PMC
January 2016

Duct-to-Duct Biliary Anastomosis Yields Similar Outcomes to Roux-en-Y Hepaticojejunostomy in Liver Transplantation for Primary Sclerosing Cholangitis.

Hepat Mon 2015 May 23;15(5):e18811. Epub 2015 May 23.

Multi Organ Transplant Unit, Departments of Medicine and General Surgery, University of Western Ontario, London, Canada.

Background: While Roux-en-Y hepaticojejunostomy (RYH) is the common anastomotic technique for liver transplantation (LT) in patients with primary sclerosing cholangitis (PSC), duct-to-duct (DD) reconstruction may be used if the recipient common bile duct is normal. There are conflicting observational data on the rate of success of DD reconstruction versus RYH, in PSC.

Objectives: The aim of this study was to assess the safety and efficacy of DD anastomosis, compared to RYH reconstruction, among adults transplanted for PSC.

Patients And Methods: All adult patients, who underwent primary LT for PSC between 1990 and 2012, were evaluated, according to type of biliary reconstruction. Recipient and graft survival, postoperative medical and surgical complications, and postoperative resource utilization rates were compared between the two groups.

Results: Totally, 73 patients fulfilled the inclusion criteria. Of them, 58 had RYH and 15 had DD reconstruction. A total of 53 subjects (73%) were male, with the mean age ± standard deviation at LT of 43.3 ± 14.4 years. Rates of recipient mortality, graft failure, biliary complications, acute cellular rejection, and reoperation were similar in both groups. Postoperative cholangiography was used more frequently in patients with DD reconstruction (33.3% vs. 8.6%, P = 0.026).

Conclusions: In selected recipients with PSC, DD reconstruction is a safe and efficacious technique, with long-term clinical outcomes comparable to RYH.
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http://dx.doi.org/10.5812/hepatmon.15(5)2015.18811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451269PMC
May 2015

An elderly lady with significant weight loss.

Arab J Gastroenterol 2015 Mar 14;16(1):31-2. Epub 2015 Mar 14.

Department of Medicine, Division of Gastroenterology, London Health Science Center, The University of Western Ontario London, Ontario, Canada; Department of Pathology, London Health Science Center, The University of Western Ontario London, Ontario, Canada.

We present a rare case of collagenous sprue in an elderly woman with significant weight loss and malnutrition. Collagenous sprue is a rare, female-predominant and immune-mediated gastrointestinal disease that can affect any part of the gut, and shares a strong association with Coeliac disease. The diagnosis is confirmed by gut histopathology demonstrating a subepithelial collagenous band and inflammatory infiltrate in the lamina propria. The pathogenesis and natural history is poorly elucidated, and treatment involves a gluten-free diet and/or immunomodulatory therapy.
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http://dx.doi.org/10.1016/j.ajg.2014.10.003DOI Listing
March 2015

Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience.

Ann Hepatol 2014 Sep-Oct;13(5):525-32

Toronto General Hospital, University of Toronto. Ontario, Canada.

Introduction: Hepatitis C (HCV) continues to be the leading indication for liver transplantation (LT). Sustained virological response (SVR) rates to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for recurrent HCV in Genotype 1 (G1) LT recipients have been disappointing (30-40%). Experience with triple therapy using protease inhibitors (PI) boceprevir (BOC), telaprevir (TVR) in these patients has been limited.

Material And Methods: This national multicenter retrospective study included 76 patients (64 male, mean age 57 ± 6 years), treated for G1 HCV recurrence with either BOC (n = 41) or TVR (n = 35), who were non-responders or relapsers (n = 54), treatment naïve (n = 22) or had fibrosing cholestatic HCV (n = 3). 53 patients were on cyclosporine, 22 on tacrolimus and one patient on prednisone alone.

Results: On treatment virologic response was observed in 84% (64/76), 83% in BOC and 85% in TVR group. A higher week 4 response after starting triple therapy (RVR) was noted in TVR group 25/35 (81%) as compared to BOC group 26/41 (63%); p value = 0.02. The end of treatment response was 78% and 75% in BOC and TVR group, respectively. SVR 12 weeks after treatment discontinuation was observed in 59.5% (22/37); 58.3% in the BOC group and 61.5% in TVR group. Treatment was discontinued early in 23 patients (serious adverse effects n = 19, treatment failure n = 4). Infections occurred in 5 patients with 2 deaths (all in BOC). Anemia was the most common side effect (n = 55, 72%) requiring erythropoietin and RBV dose reduction. In the BOC group, cyclosporine dose reduction was 2.2 ± 1.0 fold and 8.6 ± 2.4 fold with tacrolimus. In TVR group, dose reduction was 3.0 ± 1.4 with cyclosporine and 12 ± 5.7 fold with tacrolimus.

Conclusions: PI-based triple therapy appears more effective in producing HCV-RNA clearance than dual therapy. Tolerability is a serious issue and drug-drug interactions are manageable with close monitoring.
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May 2015
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