LS values at CVR are useful for predicting forthcoming LRE development. Thus, in the era of potent antiviral therapy, tailored surveillance strategies might be established based upon LS values at CVR.

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Backgrounds/Aims Monitoring fibrosis is mandatory for detailed prognostification in patients with chronic liver disease. We developed optimized cut‐offs for liver stiffness (LS) values, based on the histological subclassification of cirrhosis, and investigated whether early on‐treatment changes in LS values can predict long‐term prognosis in patients with hepatitis B virus (HBV)‐related advanced liver fibrosis receiving antiviral therapy. Methods Between 2005 and 2008, 103 patients with F3 or F4 fibrosis on liver biopsy were enrolled prospectively. Cirrhosis was subclassified into three groups (F4A, F4B and F4C) according to Laennec system. The primary end‐point was occurrence of liver‐related event (LRE), including decompensation, hepatocellular carcinoma and liver‐related death. Results Suggested LS cut‐offs for predicting F4B‐FC (vs. F3‐F4A) and F4C (vs. F3‐F4B) were 11.6 and 18.2 kPa respectively. As proportions of patients with LRE occurrence increased according to histological subclassifications stage F3‐4A vs. F4B‐4C (7.4% vs. 17.1%) and stage F3‐4B vs. F4C (13.8% vs. 18.8%), they also increased according to LS cut‐off value of 11.6 kPa (5.9% vs. 23.1%) and 18.2 kPa (9.8% vs. 33.3%) respectively (all P < 0.05). Similarly, according to stratified LS values (<11.6, 11.6–18.2 and ≥18.2 kPa), overall incidence of LREs and each constituent event increased significantly (all P < 0.05). In addition, the observed changes in LS values between baseline and 6 months of follow‐up showed significant correlations with LRE development. Conclusions Stratified LS values based on Laennec system and dynamic changes in LS values on follow‐up may be helpful in assessing risk of LREs in subjects with HBV‐related advanced liver fibrosis receiving antiviral therapy.

Serum fibrosis markers, such as the enhanced liver fibrosis (ELF) test, have been suggested as alternatives for liver biopsy (LB) in assessing liver fibrosis. We investigated the efficacy of the ELF test in predicting development of liver-related events (LREs) in patients with chronic hepatitis B (CHB). A total of 170 patients (103 men; 60.6%) with CHB who underwent LB and serological tests for determining ELFs were enrolled. All patients were followed up to monitor LRE development, defined as hepatic decompensation, hepatocellular carcinoma, and/or liver-related death. The mean age was 45.3 years. During the follow-up period (median, 41 months), 39 (22.9%) patients experienced LREs. In patients with LREs, age, proportion of male gender, ELF test results, age-spleen-platelet ratio (ASPRI), liver stiffness (LS) value, and proportion of histological cirrhosis were significantly higher than those in patients without LREs (all P < 0.05). Areas under the receiver operating characteristic curves to predict LRE development were 0.808 for the ELF test, 0.732 for LS value, 0.713 for histological fibrosis stages using Batts and Ludwig's scoring system, and 0.687 for ASPRI. On multivariate analysis, along with age, the ELF test was an independent predictor of LRE development (adjusted hazard ratio [HR], 1.438; P < 0.001). When we applied a three-tier stratification of our study population using cut-off ELF values of 8.10 and 10.40, patients with low (P 5 0.002; adjusted HR: 0.045; 95% confidence interval [CI]: 0.006-0.330) and intermediate (P < 0.001; adjusted HR: 0.239; 95% CI: 0.122-0.469) ELF range were found less likely to develop LREs, compared to those with high ELF range. Conclusion: ELF is useful in a noninvasive prediction of LRE development. Transient elastography showed a statistically similar prognostic performance for LREs as the ELF, but other noninvasive tests were inferior. (HEPATOLOGY 2014;60:1911-1919

Diabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing in mind the paucity of effective treatment for DN and progressive CKD, novel targets for treatment are sorely needed. We previously reported that increased activity of tonicity-responsive enhancer-binding protein (TonEBP) in monocytes was associated with early DN in humans. We now extend these findings by testing the hypotheses that TonEBP in macrophages promotes hyperglycemia-mediated proinflammatory activation and chronic renal inflammation leading to DN and CKD, and TonEBP genetic variability in humans is associated with inflammatory, renal, and vascular function-related phenotypes. In a mouse model of DN, compared with the wild-type phenotype, TonEBP haplodeficiency associated with reduced activation of macrophages by hyperglycemia, fewer macrophages in the kidney, lower renal expression of proinflammatory genes, and attenuated DN. Furthermore, in a cohort of healthy humans, genetic variants within TonEBP associated with renal function, BP, and systemic inflammation. One of the genetic variants associated with renal function was replicated in a large population-based cohort. These findings suggest that TonEBP is a promising target for minimizing diabetes- and stress-induced inflammation and renovascular injury.