Bandar Al-Judaibi

Toward a personalized medicine approach to the management of inflammatory bowel disease.

The medical management of inflammatory bowel disease (IBD) is evolving toward a personalized medicine-based model. Modern therapeutic algorithms that feature use of tumor necrosis factor (TNF) antagonists in combination with immunosuppressive are highly effective when initiated in high-risk patients early in the course of disease. Defined targets that guide intensification of therapy are critical interventions. In this model, therapy is optimized through appropriate pretreatment testing, therapeutic drug monitoring, and patient-based monitoring strategies. This review discusses the current application of personalized medicine to the management of IBD.

Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

Background This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. Methods One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. Results One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. Conclusions Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.

The safety and efficacy of gastric fundal variceal obliteration using N-butyl-2-cyanoacrylate; the experience of a single canadian tertiary care centre

Background/Aim: Bleeding from Gastric Varices (GV) is not only life threatening, but also leads to many hospitalizations, contributes to morbidity and is resource intensive. GV are difficult to diagnose and their treatment can be challenging due to their location and complex structure. To assess the safety and efficacy of endoscopic gastric fundal variceal gluing using periodic endoscopic injections of N-butyl-2-cyanoacylate (NBCA) and to assess the utility of endoscopic ultrasound (EUS) in assessing for the eradication of GV post-NBCA treatment. Materials and Methods: Analysis of prospectively collected data of a cohort of patients with GV who underwent periodic endoscopic variceal gluing from 2005 to 2011. Outcomes included success of GV obliteration, incidence of rebleeding, complications from the procedure, and analysis of factors that might predict GV rebleeding. The success of GV eradication was assessed by both EUS and direct endoscopy. Results: The cohort consisted of 29 consecutive patients that had undergone NBCA injection for GV. The mean age was 60.8 years standard deviations (SD 13.3, range 20-81). The average follow-up was 28 months (SD 19.61, range 1-64) and the most common cause for GV was alcoholic liver cirrhosis (34.48%). A total of 91 sessions of NBCA injections were carried out for 29 patients (average of 3.14 sessions/patient, SD 1.79, range 1-8) with a total of 124 injections applied (average of 4.28 injections/patient, SD 3.09, range 1-13). 24 patients were treated for previously documented GV bleeding while five were treated for primary prevention. Overall, 79% of patients were free of rebleeding once three sessions of histoacryl® injection were completed. None of the patients treated for primary prevention developed bleeding during follow-up. 11 of the 24 patients (46%) with previous bleeding however had rebleeding. 4/11 (36%) patients had GV rebleeding while awaiting scheduled additional NBCA sessions. 19/29 (60%) patients had complete eradication of GV, 11/19 (58%) documented by endoscopic assessment alone, 4/19 (21%) by EUS alone and 4/19 (21%) by both techniques. Two of the 11 (18%) patients that had rebleeding had recurrence of GV bleeding after documented eradication by EUS compared to 5/11 (45%) patients documented eradication by endoscopic assessment and 2/11 (18%) patients that had rebleeding after documented eradication by both modalities. Twenty five patients in total had documented residual GV by EUS (14, 56%), direct endoscopic assessment (18, 72%) or both modalities (9, 36%), two of which developed recurrent bleeding (13%). No immediate or long-term complications of NBCA injection occurred, nor any related endoscopic complications were reported in any of these cases during the time of follow-up. Conclusion: NBCA injection of GV is a safe and successful therapeutic intervention. A minimum of three endoscopic sessions is required to significantly decrease the risk of bleeding/rebleeding. In this small sample of patients, neither EUS nor direct endoscopic assessment was reliable in predicting the recurrence of GV bleeding.

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

BACKGROUND The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-plate-let-ratio-index score among HCV-patients. CONCLUSION A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.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 < 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.

An unusual case of collagenous gastritis in a middle- aged woman with systemic lupus erythromatosis: a case report

IntroductionCollagenous gastritis is a rare histopathologic disease. It is characterized by marked subepithelial collagen deposition with associated inflammatory infiltrate. It is considered an uncommon disease among the general population. Collagenous gastritis without colonic involvement is an extremely rare disease. It is not known to be associated with systemic lupus erythromatosis. This is the first report of this type of association.Case presentationWe present a 47-year-old woman from southeast Asia with dyspepsia and mild anemia. Her past medical history was significant for systemic lupus erythromatosis, autoimmune hemolytic anemia as well as hypothyroidism. Her gastroscopy and colonoscopy results were normal from an endoscopic point of view. However, the histopathology showed collagenous gastritis.ConclusionsTo the best of our knowledge, this is the first case reported of a patient with systemic lupus erythromatosis associated with collagenous gastritis. Further studies are needed to evaluate the association between both diseases from a pathophysiological and immunological perspective.

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

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.

Abernethy malformation: Congenital absence of the portal vein

1Department of Internal Medicine; 2Department of Gastroenterology and Hepatology, Western University, London, Ontario; 3Department of Gastroenterology, King Khalid University Hospital, King Saud University, Saudi Arabia Correspondence: Dr Lukasz Kwapisz, Department of Internal Medicine, Western University, 147 Ocean Pearl Street, Whitby, Ontario L1N 0C7. Telephone 226-919-4034, e-mail lukaszkwapisz84@hotmail.com Received for publication June 29, 2014. Accepted September 17, 2014 CASE PRESENTATION A 20-year-old previously well man presented with unintentional 6.75 kg (15 lb) weight loss over a six-month period, vague abdominal discomfort and bilateral patchy rash. Blood work was notable for elevations in alanine aminotransferase (75 U/L [normal range <41 U/L]), aspartate aminotransferase (101 U/L [<40 U/L]), alkaline phosphatase (310 U/L [40 U/L to 129 U/L]) and total bilirubin (15.7 μmol/L [3.4 μmol/L to 17 μmol/L]) levels. An abdominal ultrasound revealed hepatic nodules. On further characterization, magnetic resonance imaging revealed a portosystemic shunt (PSS) between the main portal vein and inferior vena cava (IVC) (Figure 1). Both vessels were dilated, with no definite intrahepatic portal venous branches identified (Figure 2). Multiple large regenerative nodules could also be identified. Hepatic portal venous Doppler confirmed an extrahepatic PSS, with a markedly distended infrahepatic IVC (Figure 3). The confluence of the splenic vein and superior mesenteric vein drained directly into the IVC. The morphology suggested a type Ib Abernethy malformation.

Hepatic metastasis from adrenocortical carcinoma fifteen years after primary resection

We report the case of a 73-year-old man who presented with an asymptomatic hepatic mass during investigation of mild chronic obstructive pulmonary disease by a plain chest radiograph, followed by ultrasonography, which revealed a solitary hepatic lesion measuring 7.1 cm × 6.5 cm × 5.8 cm in dimension. Fine- needle aspiration of the mass revealed malignant cells compatible with hepatocellular carcinoma. Interestingly, the patient had a left adrenalectomy and complete left nephrectomy in 1987, for a non-functioning left adrenocortical carcinoma (ACC). The ACC was diagnosed as stage two, with no evidence of local invasion or distant metastases. No adjuvant therapy was recommended postoperatively. After a five-year follow-up, there was no evidence of ACC recurrence and the patient was declared cured from his ACC. The patient underwent a complete segmental resection of the right lobe of the liver successfully. The final diagnosis of the mass was a well-differentiated metastatic adrenocortical carcinoma.

Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.

Background/Aim: In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence. Patients and Methods: A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed. Results: A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years’ post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007). Conclusions: This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.

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

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%, p > 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, p < 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.