Apoptotic and anti-apoptotic seromarkers for assessment of disease severity of non-alcoholic steatohepatitis

This study aimed to find out non-invasive markers for the assessment of severity of non-alcoholic steatohepatitis [NASH] in an attempt to decrease the need for liver biopsy. It also aimed to evaluate the key role of apoptosis in the pathogenesis of the disease and the suggested role of anti-apoptotic factors in therapeutic modalities and disease prognosis. The serum levels of soluble Fas [s. Fas], s. Fas ligand, cytokeratin 18 [CK-18] fragment and Bcl-2 were measured in 80 patients and 15 non-hepatic subjects as control. The patients were divided based on histological examination of liver biopsy into three groups. Group I included 40 patients with NASH, group II had 40 patients with non-alcoholic fatty liver disease [NAFLD] non-NASH and group III had 15 non-hepatic subjects as control. Apoptosis of hepatocytes was assessed by morphological examination using a light microscope and expressed as number per square millimeter. There was a significant increase in the serum levels of s. Fas, s. Fas ligand and CK-18 fragments in the NASH group. The anti-apoptotic protein Bcl-2 showed significantly low levels in NASH patients. Apoptosis of hepatocytes was significantly higher in the NASH group. The degree of apoptosis was inversely correlated with the level of Bcl-2. A significant correlation between both s. Fas and CK-18 fragment with liver histology with regard to lobular inflammation and ballooning was found. Increased serum levels of s. Fas and CK-18 fragment in the NASH group and its correlation with the severity of disease suggested the key role of apoptosis in NASH pathogenesis which can be used for the assessment of the severity of NASH. A high level of anti-apoptotic Bcl-2 in NAFLD suggests its protective role in disease progress

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy

Minimal hepatic encephalopathy [MHE] is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probi-otics as alternative therapy in MHE. This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic [Lactobacillus acidophilus] and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy [MRS] examination to study brain metabolites, mainly choline [Cho], myoinositol [ml], glutamine + glutamate [Glx] and creatinin [Cre]. Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4 weeks. The probiotic was better tolerated than lactulose. The relative risk reduction [RRR] of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat [NNT] of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The ml/Cre and [Cho + mI]/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1 month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group

Fibrosis severity and mannan-binding lectin [MBL]/MBL associated serine protease 1 [MASP-1] complex in HCV-infected patients

Mannan-binding lectin [MBL] is a collectin synthesised in the liver and secreted into the bloodstream. It binds micro-organisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes [MASPs]. Several studies have investigated the possible role for MBL in hepatitis C virus [HCV] infection by examining MBL levels and polymorphisms in relation to disease progression and in response to treatment. The aim of this study was to investigate the relation of the activity of MBL and MBL/MASP-1 complex in sera of patients with mild and severe chronic HCV infection and outcome of HCV infection. Serum level of MBL and functional assays for MBL/MASP-1 complex activity were assayed in sera of 80 patients with chronic HCV infection. Patients were divided into two groups according to the results of the liver biopsy, group I [40 HCV patients had mild hepatic fibrosis, Ishak fibrosis stages 0-1] and group II [40 HCV patients had severe hepatic fibrosis, Ishak fibrosis stages 5-6], in addition to 20 control subjects as group III. The analysis of the MBL/MASP-1 complex activity at 0, 3 and 6 months was performed in all patients. Serum levels of MBL and MBL/MASP-1 complex activity were higher in sera of patients with chronic HCV liver disease compared to those in control subjects. There was a correlation between the activity of the MBL/MASP-1 complex and the severity of fibrosis [P= 0.003]. MBL/MASP-1 complex activity was associated more significantly with severe fibrosis in comparison to MBL concentration. MBL and MBL/MASP-1 complex activities play a key role in first-line host defence mechanism against certain infectious agents including HCV infection. However, it is also likely that the role of MBL and MBL/MASP-1 complex activity extends beyond this restricted infection-related view in that it appears to be a key regulator of inflammation