Bastiaan de Boer

Validation of the FibroTest Biochemical Markers Score in Assessing Liver Fibrosis in Hepatitis C Patients

BACKGROUND Determining the stage of fibrosis by liver biopsy is important in managing patients with hepatitis C virus infection. We investigated the predictive value of the proprietary FibroTest score to accurately identify significant fibrosis in Australian hepatitis C patients. METHODS Serum obtained from 125 confirmed hepatitis C patients before antiviral therapy was analyzed for haptoglobin, alpha(2)-macroglobulin, apolipoprotein A1, bilirubin, and gamma-glutamyltransferase activity, and the FibroTest score was computed. Liver fibrosis pathology was staged according to a defined system on a scale of F0 to F4. We used predictive values and a ROC curve to assess the accuracy of FibroTest scores. RESULTS The prevalence of significant fibrosis defined by liver biopsy was 0.38. The most useful single test for predicting significant fibrosis was serum alpha(2)-macroglobulin (cutoff value, 2.52 g/L; sensitivity, 75%; specificity, 67%). The negative predictive value of a FibroTest score <0.1 was 85%, and the positive predictive value of a score >0.6 was 78%. Although 33 of the 125 patients had FibroTest scores <0.1 and were therefore deemed unlikely to have fibrosis, 6 (18%) had significant fibrosis. Conversely, of the 24 patients with scores >0.6 who were likely to have significant fibrosis, 5 (21%) had mild fibrosis. Of the 125 patients in the cohort, 57 (46%) could have avoided liver biopsy, but discrepant results were recorded in 11 of those 57 (19%). CONCLUSION The FibroTest score could not accurately predict the presence or absence of significant liver fibrosis.

Prediction of morbidity and mortality in patients with chronic hepatitis C by non-invasive liver fibrosis models

Liver fibrosis is prognostic of outcomes among patients with chronic hepatitis C (CHC). We evaluated the accuracy of non‐invasive markers and liver biopsy in predicting morbidity and mortality in CHC patients.

Laparoscopic surgery for orthotopic kidney transplant in the pig model.

BACKGROUND Laparoscopic surgery has become the preferred approach in surgical practice due to multiple benefits. Over the last decade, kidney transplant by laparoscopic or robotic techniques have been explored. The aim of this study is to establish a new laparoscopic technique for kidney orthotopic transplant. MATERIALS AND METHODS The study was approved by the Animal Ethics Committee of the University. Ten live female pigs (Sus scrofa), weighing 45-50 kg, underwent laparoscopic kidney orthotopic transplant on left side under general anesthesia, and the opposite right kidney was defunctioned by complete ligation of the ureter at the same time. RESULTS The vital signs of all pigs were stable during the surgery and postoperative period. There were no intraoperative complications and no conversion to open surgery. The laparoscopic kidney transplant was successful in seven of 10 pigs. Seven pigs were observed up to 4 wk as planned in the study. DISCUSSION To our knowledge, this is the first study of laparoscopic kidney orthotopic transplant in pig model with satisfactory immediate graft function. It was demonstrated that laparoscopic kidney transplant is a feasible, reliable, and safe procedure. However, it is a very demanding technique. Adequate training is mandatory for performing laparoscopic kidney transplant. This study could be used as a training model for surgeons who wish to perform human laparoscopic kidney transplant in the future.

Domestically acquired hepatitis e successfully treated with ribavirin in an Australian liver transplant recipient

A 48-year-old Australian man of European ancestry received his third liver transplant in February 2013 for hepatic failure precipitated by ischaemic cholangiopathy and secondary biliary cirrhosis. His first liver transplant was performed 10 years earlier for complications of cirrhosis arising from autoimmune hepatitis – primary sclerosing cholangitis overlap syndrome, but required retransplantation after 3 months due to hepatic vein thrombosis and hepatic infarction. The second liver transplant was complicated by hepatic artery thrombosis, resulting in ischaemic cholangiopathy.

Iron-induced oxidative rat liver injury after non-heart-beating warm ischemia is mediated by tumor necrosis factor α and prevented by deferoxamine.

This study investigated iron‐induced injury after warm ischemia in a non–heart‐beating (NHB) rat liver model and the effects of deferoxamine (DFO). Livers from heart‐beating (HB) rats or rats that were NHB for 60 minutes were stored in University of Wisconsin solution for 5 hours at 4°C [cold storage (CS)] and then were subjected to 2 hours of machine reperfusion (MRP) at 37°C. Three NHB groups were compared: (1) no DFO, (2) DFO 30 minutes before cardiac arrest and during CS and MRP, and (3) DFO during CS and MRP. Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the NHB perfusate were significantly elevated (P < 0.01) in comparison with levels in HB controls after CS and MRP. After CS, the levels of iron and tumor necrosis factor α (TNF‐α) were 0.077 ± 0.007 μmol/g and 151 ± 26 pg/g, respectively, in the NHB group and 0.022 ± 0.004 μmol/g and 17 ± 7 pg/g, respectively, in the HB group (P < 0.01). After MRP, LDH significantly correlated with iron (R2 = 0.81, P < 0.01). The DFO pretreatment of NHB donors decreased AST (7.3 ± 0.8 versus 4.0 ± 0.5 U/g of liver, P < 0.05) and LDH (42.5 ± 4.1 versus 20.4 ± 2.5 U/g of liver, P < 0.05) with 2 hours of MRP and increased bile flow during MRP (142 ± 34 versus 240 ± 18 μL/g, P < 0.05). It also reduced the levels of iron (0.077 ± 0.007 versus 0.050 ± 0.008 μmol/g, P < 0.05) and TNF‐α (151 ± 26 versus 51 ± 13 pg/g, P < 0.05) after CS and the levels of lipid peroxidation products F2‐isoprostane (149 ± 11 versus 99 ± 10 ng/g, P < 0.05) and malondialdehyde (1.58 ± 0.1 versus 1.14 ± 0.08 μmol/g, P < 0.05) after MRP. In conclusion, iron‐initiated oxidative stress is likely involved in NHB donor liver injury, and importantly, DFO pretreatment reduces liver damage. Liver Transpl 20:904–911, 2014.

Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease

INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non‐alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced. RESULTS: Among 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3‐60) g over an average of 18 years. Modest consumption (1‐70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14‐0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a binge‐type fashion. Exclusive wine drinkers but not exclusive beer drinkers, had lower mean fibrosis stage and lower odds of advanced fibrosis (OR 0.20, 95% CI 0.06‐0.69, p = 0.01), compared to lifetime abstinent subjects. No interaction between gender and alcohol quantity, type, or binge consumption on fibrosis was observed. DISCUSSION: Modest (1‐70 g per week) alcohol consumption, particularly wine in a non‐binge pattern, is associated with lower fibrosis in patients with NAFLD. Prospective longitudinal studies into fibrosis progression, cardiovascular outcomes, and mortality are required before clinical recommendations can be made.

Diabetes impacts prediction of cirrhosis and prognosis by non-invasive fibrosis models in non-alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) patients with diabetes are at increased risk of cirrhosis and liver‐related death, and thus accurate fibrosis assessment in these patients is important. We examined the ability of non‐invasive fibrosis models to determine cirrhosis and outcomes in NAFLD patients with and without diabetes.