Schouten, J.N.

External Validation of the Fatty Liver Index for Identifying Nonalcoholic Fatty Liver Disease in a Population-based Study (Article)

2013-04-09T00:00:00Z

Background & Aims: We aimed to validate the fatty liver index (FLI), an algorithm that is based on waist circumference, body mass index, and levels of triglyceride and γ-glutamyltransferase. We calculated its ability to identify fatty liver disease from any cause or nonalcoholic fatty liver disease (NAFLD) in a large population of white elderly persons. Methods: We collected ultrasonography and FLI data from participants of the Rotterdam Study from February 2009 to February 2012; 2652 subjects (mean age, 76.3 ± 6.0 years) were interviewed and received a clinical examination that included abdominal ultrasound, analysis of blood samples during fasting, and anthropometric assessment. The ability of the FLI to detect (nonalcoholic) fatty liver was assessed by using area under the receiver operator characteristic (AUROC) curve analysis. Results: FLI score was associated with NAFLD in multivariable analysis (odds ratio, 1.05; 95% confidence interval [CI], 1.04-1.05; P < .001). FLI identified patients with NAFLD with an AUROC curve of 0.813 (95% CI, 0.797-0.830) and those with fatty liver from any cause with an AUROC curve of 0.807 (95% CI, 0.792-0.823). Conclusions: The FLI (an algorithm that is based on waist circumference, body mass index, and levels of triglyceride and γ-glutamyltransferase) accurately identifies NAFLD, confirmed via ultrasonography, in a large, white, elderly population.

Letter: Non-cirrhotic portal hypertension and end-stage liver disease - Authors' reply (Article)

2012-10-01T00:00:00Z

Risk factors and outcome of HIV-associated idiopathic noncirrhotic portal hypertension (Article)

2012-09-17T00:00:00Z

Background: Idiopathic noncirrhotic portal hypertension (INCPH) has been reported increasingly in patients with HIV infection. Aim: To evaluate the number of nationwide diagnosed HIV-associated INCPH cases and to assess its clinical features, risk factors and outcome. Methods: All HIV centres in the Netherlands were contacted and requested to notify INCPH cases diagnosed in their population. A case-control study was performed to identify the risk factors of INCPH. The cases were group-matched for duration of follow-up after HIV diagnosis to controls. Controls were selected from a database of HIV patients with negative screening for signs of portal hypertension on abdominal ultrasound. Univariate and multivariate conditional logistic regression analyses were performed. Results: On 1st of July 2011, 18.085 individuals were infected with HIV in the Netherlands. Within this population, sixteen patients with clinically overt INCPH were identified. At the time of INCPH diagnosis, cases had a lower platelet count and a higher ALT level. In univariate and multivariate analyses, didanosine [OR: 1.9 (1.3-2.8)], concomitant didanosine and stavudine treatment [OR: 6.3 (2.1-19.1)] and concomitant didanosine and tenofovir treatment [OR: 5.1 (1.2-22.6)] were independently associated INCPH. During follow-up, 4 patients died [malignancy (n = 3), liver failure (n = 1)]. A significant decline in platelets was observed after didanosine discontinuation (P = 0.003). Conclusions: HIV-associated clinically relevant idiopathic noncirrhotic portal hypertension appears to be a rarely diagnosed disease. Long-term exposure to didanosine and short-term combination of didanosine and stavudine or tenofovir exposure are associated with idiopathic noncirrhotic portal hypertension. Mortality in HIV-associated idiopathic noncirrhotic portal hypertension is mainly related to HIV-associated disorders. Portal hypertension continues despite didanosine discontinuation.

Risk factors and outcome of HIV-associated idiopathic noncirrhotic portal hypertension (Article)

2012-09-17T00:00:00Z

Reply (Article)

2011-12-01T00:00:00Z

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma (Article)

2011-11-01T00:00:00Z

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10-8to P = 10-190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

Idiopathic noncirrhotic portal hypertension (Article)

2011-09-02T00:00:00Z

Idiopathic noncirrhotic portal hypertension (INCPH) is characterized by an increased portal venous pressure gradient in the absence of a known cause of liver disease and portal vein thrombosis. In contrast to the high prevalence of this disorder in India, INCPH is a rare disease in the Western world. The etiology of INCPH can be divided in five categories: chronic infections, exposure to medication or toxins, thrombophilia, immunological disorders, and genetic disorders. Multifactorial etiology can also be encountered. Chronic abdominal infection is incriminated as the most important etiological factor in Eastern patients and thrombophilia in Western patients. The majority of patients with INCPH initially present with signs or complications of portal hypertension (mainly variceal bleeding and splenomegaly). These patients usually have preserved liver function. Liver function impairment occurs mainly in the context of intercurrent conditions. Patients with INCPH are often clinically and radiologically misdiagnosed as liver cirrhosis, so that a liver biopsy is indispensable to discriminate cirrhosis from INCPH. Histopathological characteristics of INCPH are heterogeneous, demonstrating overlap between several pathological entities (e.g., hepatoportal sclerosis, nodular regenerative hyperplasia, and incomplete septal cirrhosis). Even though hemodynamical changes in INCPH patients are not comparable to those in cirrhotics, prophylaxis and treatment of variceal bleeding are recommended to be similar. Anticoagulation therapy must be considered only in patients who develop portal vein thrombosis. INCPH has been considered a disorder with a relatively benign disease course. However, liver failure, hepatic encephalopathy, and hepatopulmonary syndrome can occur and are considered indications for liver transplantation.