Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease.Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively.A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate.This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.

Comparison study between open and laparoscopic liver resection in a Saudi tertiary center.

OBJECTIVES: To compare King Saud University Medical City experience in laparoscopic liver resection with our previously established database for open resections. METHODS: A retrospective study was conducted at King Saud University Medical City, Riyadh, Saudi Arabia. All adult patients who underwent liver resection from 2006 to 2017 were included. Patients who had their procedure converted to open were excluded. RESULTS: Among the 111 liver resections included, 22 (19.8%) were performed laparoscopically and 89 (80.1%) were performed using the open technique. Malignancy was the most common indication in both groups (78.5%). The mean operative time was 275 min (SD 92.2) in the laparoscopic group versus 315 min (SD 104.3) in the open group. Intraoperative blood transfusion was required in the laparoscopic (9%) and open groups (31.4%). The morbidity rate was 13.6% in the laparoscopic group and 31.4% in the open group, and the mortality rate was 0% in the laparoscopic group and 5.6% in the open group. CONCLUSION: Laparoscopic liver resection appears to be a safe technique and can be performed in various benign and malignant cases.

Morbidity and mortality and predictors of outcome following hepatectomy at a Saudi tertiary care center.

BACKGROUND: Hepatic resection is a major surgical procedure. Data on outcomes of hepatectomy in Saudi Arabia are scarce. OBJECTIVE: To measure morbidity and mortality and assess predictors of outcome after hepatectomy. DESIGN: Descriptive study. SETTING: Tertiary care center in Saudi Arabia with well established hepatobiliary surgery unit. PATIENTS AND METHODS: All patients undergoing liver resection in our institute during 2006-2014. Data were analyzed by Kaplan-Meier survival analysis. MAIN OUTCOMES MEASURE(S): Postoperative morbidity and 90-day mortality. Secondary outcomes were risk factors associated with increased morbidity and mortality. RESULTS: Data on 77 resections were collected; 56 patients (72.7%) had a malignant etiology, mainly colorectal liver metastases and hepatocellular carcinoma (45.5% and 14.3% respectively). Complications developed following 30 resections (39.0%), with the majority being Clavien grades I-III. In the univariate analysis, predicting factors were the total bilirubin level preoperatively, operative time, extent of resection (i.e., major resection), use of epidural anesthesia, and postoperative liver dysfunction. In the multivariate analysis, the Schindl liver dysfunction score showed the strongest correlation with the development of complications (P=.006). The 90-day postoperative mortality was 5.2% (4/77 patients); 3 patients fulfilled the 50:50 liver dysfunction criteria. Significant predictors were concurrent intra-abdominal surgery, postoperative liver dysfunction, and multiple complications. CONCLUSION: Factors that predicted development of complications were elevated total bilirubin level preoperatively, operative time, extent of the resection, use of epidural anesthesia and a postoperative need for blood transfusion. Liver resection is a safe and feasible option at our center. LIMITATIONS: The small number of indications for resection and consequent reduction in variety of risk factors limited ability to make inferences. Additionally, only a handful of cases were performed laparoscopically.

Recipient characteristics and outcome of pediatric kidney transplantation at the King Fahad Specialist Hospital-Dammam.

The success of a pediatric kidney transplantation program can only be judged by reviewing its results. We aim to audit our short-term outcome of pediatric kidney transplantation at the King Fahad Specialist Hospital-Dammam. A retrospective chart review was performed to collect data about recipient demographics, etiology of end-stage kidney disease, type of dialysis, type of donor and outcome. Between September 2008 and April 2012, 35 pediatric kidney trans-plantations (<16 year) were performed of a total of 246 kidney transplants (14.2%). The mean age was 8.1 years, with a mean weight of 23.3 kg, and there were 21 (60%) boys in the study. Kidney dysplasia/hypoplasia was the most common etiology (51.4%). Preemptive kidney transplantation was performed in six (17%) patients. Peritoneal dialysis was the most common mode of dialysis [24 (69%) children]. Living donation was the source of kidney allografts in 13 (37%) cases. During a mean follow-up of 1.5 years, one patient died and one graft was lost due to kidney vein thrombosis. The one year patient and graft survival rates were 97% and 94%, respectively. Efforts should now be focused on achieving optimal long-term results. There is also a need to encourage preemptive transplantation and living donation in this population.

Assessment of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma in Middle Eastern patients.

BACKGROUND: Alpha-fetoprotein (AFP) levels for the diagnosis of hepatocellular carcinoma (HCC) may vary by geographical region and racial background. No data exists for this test in the Middle Eastern population. In addition, there is limited data on the impact of virological status on AFP levels. METHODS: In a multicenter, case-control study involving 206 cases, 199 cirrhotic and 197 chronic hepatitis controls, we assessed the utility of AFP in the diagnosis of HCC (sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive likelihood ratios (LR). PPV and NPV were evaluated for three additional HCC prevalence rates (5, 10, and 20%). RESULTS: The best discriminating AFP value was 11.7 ng/ml. The sensitivity ranged from 32 to 79.5% at different AFP levels with the specificity increasing sequentially from 47.7 to 98.5%. Sensitivity of AFP at the best cut-off level for hepatitis C virus (HCV), hepatitis B virus (HBV) and non-viral etiology for HCC was 73.7, 65.6, and 59.5%, respectively. Specificity at this level for HCV, HBV, and non-viral etiology was 36.6, 30.1, and 29.4%, respectively. AFP cut-off levels of 102, 200, and 400 ng/ml showed similar sensitivity (39.8, 35.9, and 32%, respectively) and specificity (96, 98.5, and 98.5% respectively). Positive LR for AFP at >11.7, >20, >102, >200, >400 ng/ml were 2.8, 3.3, 9.9, 23.8, and 21.2, respectively. CONCLUSIONS: In cirrhotic patients, AFP has a poor screening and diagnostic value for HCC. Underlying viral etiology fails to influence the diagnostic accuracy of this test. An AFP level greater than 100 ng/ml has a high degree of specificity and may be used as a confirmatory test.

Portal vein embolization with radiolabeled polyvinyl alcohol particles in a swine model: hepatic distribution and implications for pancreatic islet cell transplantation.

The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 microm (Contour SE) and labeled with (99m)Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for (99m)Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulate labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 +/- 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with (99m)Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-microm particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.

Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide.

Although insulin independence is maintained in most islet recipients at 1 yr after transplant, extended follow-up has revealed that many patients will eventually require insulin therapy. Previous studies have shown that islet autografts are prone to chronic failure in large animals and humans, suggesting that nonimmunological events contribute to islet graft functional decay. Early intervention with therapies that promote graft stability should provide a measurable benefit over time. In this study, the efficacy of the long-acting glucagon-like peptide-1 analog liraglutide was explored in a porcine marginal mass islet autograft transplant model. Incubation with liraglutide enhanced porcine islet survival and function after prolonged culture. Most vehicle-treated (83%) and liraglutide-treated (80%) animals became insulin independent after islet autotransplantation. Although liraglutide therapy did not improve insulin independence rates or blood glucose levels after transplant, a significant increase in insulin secretion and acute-phase insulin response was observed in treated animals. Surprisingly, no evidence for deterioration of graft function was observed in any of the transplanted animals over more than 18 months of follow-up despite significant weight gain; in fact, an enhanced response to glucose developed over time even in control animals. Histological analysis showed that intraportally transplanted islets remained highly insulin positive, retained alpha-cells, and did not form amyloid deposits. This study demonstrates that marginal mass porcine islet autografts have stable long-term function, even in the presence of an increasing metabolic demand. These results are discrepant with previous large animal studies and suggest that porcine islets may be resistant to metabolic failure.

Adult intussusception: a retrospective review.

PURPOSE: Whereas intussusception is relatively common in children, it is clinically rare in adults. The condition is usually secondary to a definable lesion. This study was designed to review adult intussusception, including presentation, diagnosis, and optimal treatment. METHODS: A retrospective review of 22 cases of intussusception occurring in individuals older than aged 18 years encountered at two university-affiliated hospitals in Winnipeg between 1989 and 2000. The 22 cases were divided to benign and malignant enteric, ileocolic, colonic lesions respectively. The diagnosis and treatment of each case were reviewed. RESULTS: There were 22 cases of adult intussusception. Mean age was 57.1 years. Abdominal pain, nausea, and vomiting were the commonest symptoms. There were 14 enteric, 2 ileocolic, and 6 colonic intussusceptions. Eighty-six percent of adult intussusception was associated with a definable lesion. Twenty-nine percent of enteric lesions were malignant. All ileocolic lesions were malignant. Of colonic lesions, 33 percent were malignant and 67 percent were benign. All cases required surgical interventions except one. CONCLUSIONS: Adult intussusception is a rare entity and requires a high index of suspicion. Our review supports that small-bowel intussusception should be reduced before resection if the underlying etiology is suspected to be benign or if the resection required without reduction is deemed to be massive. Large bowel should generally be resected without reduction because pathology is mostly malignant.

Sirolimus-induced ulceration of the small bowel in islet transplant recipients: report of two cases.

Sirolimus (SRL) has been used for most islet recipients over the past 5 years. It provides balanced immunosuppression in combination with low-dose calcineurin inhibitors, while avoiding corticosteroids. This regimen decreases the risk of nephrotoxicity, neurotoxicity and diabetogenicity. SRL has also been used selectively in clinical liver and kidney transplantation. A number of common side effects including anemia, leucopenia, thrombocytopenia, hypercholesterolemia, mouth ulceration, joint pain, extremity edema and impaired wound healing have been associated with the use of SRL. As SRL is used more frequently, evidence has been gathered on its rare but severe side effects. We report 2 patients who underwent islet transplantation and developed symptomatic small bowel ulceration that resolved after complete withdrawal of SRL. Although small bowel ulceration is rare, it can potentially progress to more serious complications if not treated adequately. Our experience highlights an uncommon but potentially serious adverse effect of high-dose SRL in islet recipients.