Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease, coupled with metabolic syndrome, which may progress to non-alcoholic steatohepatitis (NASH). Diabetes, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia are considered to be the most common causes leading to the incidence of NAFLD. It is assumed that the accumulation of lipid deposits in hepatocytes leads to production of proinflammatory cytokines that triggers the development of liver inflammation. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in NASH, while T helper type 17 (Th17) might functionally oppose Treg-mediated responses. In addition, important mediators of hepatic steatosis are fatty hormones known as adipokines. We aimed to describe the significance and interaction between Treg and Th17-related cytokines as well as adipokines in pathogenesis and its potential use as biomarkers of NAFLD, especially with respect to progression to NASH.

Background: Minimal hepatic encephalopathy (MHE) refers to a number of neuropsychiatric and neurophysiological disorders in patients with cirrhosis who do not show abnormalities on physical examination or in clinical tests. The aim of this study was to determine the prevalence, risk factors, and predictive value of minimal hepatic encephalopathy and the usefulness of the inhibitory control test (ICT) in the diagnosis. Methods: Seventy patients (mean age 53 years, range 24−77) with liver cirrhosis were enrolled in the study. MHE was diagnosed based on PHES (psychometric hepatic encephalopathy score) and ICT. PHES and ICT were validated in a group of 56 control subjects. Results: Minimal hepatic encephalopathy was diagnosed using PHES in 21 patients (30%). ICT diagnosed MHE in 30 patients (42%), and the test had a sensitivity of 65% and a specificity of 57% compared to PHES. The ICT score (lures/target accuracy rate) correlated with the age of subjects (R = 0.35, p = 0.002) and only slightly with education (education in years R = −0.22, p = 0.06). MHE diagnosed with PHES or ICT was associated with a significantly higher model of end-stage liver disease (MELD) score in the follow-up. MHE diagnosed with ICT was correlated with a significantly higher incidence of symptoms of decompensated cirrhosis (p = 0.02) in the follow-up. Conclusions: ICT had moderate sensitivity and specificity in diagnosing MHE compared to PHES. Importantly, MHE detected with PHES or ICT was associated with poorer survival and a more severe progression of the disease.

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

In this study, the catechol 2,3-dioxygenase gene that encodes a 307- amino-acid protein was cloned from Planococcus sp. S5. The protein was identified to be a member of the superfamily I, subfamily 2A of extradiol dioxygenases. In order to study residues and regions affecting the enzyme's catalytic parameters, the c23o gene was randomly mutated by error-prone PCR. The wild-type enzyme and mutants containing substitutions within either the C-terminal or both domains were functionally produced in Escherichia coli and their activity towards catechol was characterized. The C23OB65 mutant with R296Q substitution showed significant tolerance to acidic pH with an optimum at pH 5.0. In addition, it showed activity more than 1.5 as high as that of the wild type enzyme and its K_m was 2.5 times lower. It also showed altered sensitivity to substrate inhibition. The results indicate that residue at position 296 plays a role in determining pH dependence of the enzyme and its activity. Lower activity toward catechol was shown for mutants C23OB58 and C23OB81. Despite lower activity, these mutants showed higher affinity to catechol and were more sensitive to substrate concentration than nonmutated enzyme.

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