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Background & Aims: Studies have described prominent histologic improvement in patients with nonalcoholic steatohepatitis (NASH) using thiazolidinedione (TZD); however, these were all short term with moderate sample size, no liver‐related long‐term outcomes could be noted. Methods: This retrospective cohort study enrolled patients with newly diagnosed type 2 diabetes mellitus (T2DM) from Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2013. We matched TZD users and nonusers at a 1:1 ratio through propensity score matching. This study included 5095 paired TZD users and nonusers. Cox proportional hazard models were used to compare the risks of cirrhosis, hepatic decompensation, hepatic failure and all‐cause mortality between TZD users and nonusers. The Kaplan‐Meier method was used to compare the cumulative incidence of these main outcomes. Results: The incidence rates of cirrhosis, hepatic decompensation, hepatic failure and all‐cause mortality during follow‐up were 0.77 vs 1.95, 1.43 vs 1.75, 0.36 vs 0.70, and 4.89 vs 3.78 per 1000 person‐years between TZD users and nonusers. The adjusted hazard ratios of cirrhosis, hepatic decompensation, hepatic failure and all‐cause mortality were 0.39 (95% confidence interval [CI]: 0.21‐0.72), 0.86 (95% CI: 0.52‐1.44), 0.46 (95% CI: 0.18‐1.17) and 1.18 (95% CI: 0.87‐1.61) respectively. Conclusions: Our study demonstrated that TZD use could significantly lower the risk of cirrhosis. In clinical settings, TZD use might be able to improve liver‐related long‐term outcomes. [ABSTRACT FROM AUTHOR]

Background & Aims Sleep preparation/onset are associated with peripheral vasodilatation and a decrease in body temperature. The hyperdynamic syndrome exhibited by patients with cirrhosis may impinge on sleep preparation, thus contributing to their difficulties falling asleep. The aim of this study was the assessment of skin temperature, in relation to sleep-wake patterns, in patients with cirrhosis. Methods Fifty-three subjects were initially recruited, and 46 completed the study. Of the final 46, 12 were outpatients with cirrhosis, 13 inpatients with cirrhosis, 11 inpatients without cirrhosis and 10 healthy volunteers. All underwent baseline sleep-wake evaluation and blood sampling for inflammatory markers and morning melatonin levels. Distal/proximal skin temperature and their gradient ( DPG) were recorded for 24 hours by a wireless device. Over this period subjects kept a sleep-wake diary. Results Inpatients with cirrhosis slept significantly less well than the other groups. Inpatients and outpatients with cirrhosis had higher proximal temperature and blunted rhythmicity compared to the other groups. Inpatients with/without cirrhosis had higher distal temperature values and blunted rhythmicity compared to the other groups. Inpatients and outpatients with cirrhosis had significantly lower DPG values compared to the other groups, and DPG reached near-zero values several hours later. Significant correlations were observed between temperature and sleep-wake variables and inflammatory markers. Conclusions Alterations of distal/proximal skin temperature, their gradient and their time-course were observed in patients with cirrhosis, which may contribute to their sleep disturbances. [ABSTRACT FROM AUTHOR]

Background & Aims Serum concentrations of miR-122 were proposed as a marker for various inflammatory diseases, but the mechanisms driving alterations in miR-122 serum levels are unknown. Methods We analysed miR-122 serum levels and hepatic miR-122 expression in mice after hepatic ischaemia and reperfusion (I/R) injury. These data were compared with data from mice after caecal pole ligation and puncture ( CLP) procedure. To translate these data into the human, we analysed miR-122 serum concentrations in a cohort of 223 patients with critical illness and 57 patients with cirrhosis. Results We detected strongly elevated levels of miR-122 in mice after hepatic I/R injury. miR-122-concentrations correlated with the degree of liver damage according to AST/ ALT and were associated with the presence of hepatic cell death detected by TUNEL staining. miR-122 levels were elevated in the cellular supernatants in an in vitro model of hepatocyte injury, supporting the hypothesis that the passive release of miR-122 represents a surrogate for hepatocyte death in liver injury. Moreover, miR-122 levels were almost normal in patients with cirrhosis without ongoing liver damage, but were elevated when liver injury was present. In contrast to previous assumptions, miR-122-concentrations were independent of the presence of infection/sepsis in mice or human patients. miR-122 levels did not correlate with disease severity or mortality in critically ill patients. In contrast, serum miR-122 levels strictly correlated with the presence of hepatic injury in these patients. Conclusion In mice and humans, miR-122 levels represent an independent and potent marker of ongoing liver injury and hepatic cell death regardless of the underlying disease. [ABSTRACT FROM AUTHOR]

Imazeki F, Yokosuka O, Fukai K, Kawai S, Kanda T, Kojima H, Saisho H. Lower incidence of hepatic failure than hepatocellular carcinoma in Japanese patients with chronic Hepatitis C. Liver International DOI: 10.1111/j.1478-3231.2005.01062x. © Blackwell Munksgaard 2005 Previous studies have shown that the development of hepatic failure was found more frequently than that of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C in the United States and European countries. We investigated the status in Japan in a retrospective cohort study. The incidences of HCC and hepatic failure were accessed in 459 patients with biopsy-proven C-viral chronic liver disease with a mean follow-up period of 8.9±3.2 years and the cause of death was also analyzed in the cohort. HCC developed in 63 patients, 46 of 355 interferon (IFN)-treated and 17 of 104 untreated patients. In contrast, the development of hepatic failure was found in 18 patients, 12 of 355 IFN-treated and six of 104 untreated patients. HCC developed in four of 116 with sustained virological response (SVR), and hepatic failure developed in one of them. Thirty-two of 63 patients developing HCC and eight of 18 patients developing hepatic failure died. Development of hepatic failure was less frequent than that of HCC in Japan. It is important for a favorable prognosis of patients with C viral chronic liver disease to achieve a higher SVR and thus inhibit the development of HCC in Japan. [ABSTRACT FROM AUTHOR]

Rittler P, Ketscher C, Inthorn D, Jauch K-W, Hartl WH. Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction – preliminary results. Liver International 2004: 24: 136–141. © Blackwell Munksgaard 2004 Molecular adsorbent recycling system (MARS) has been applied successfully in patients with a variety of liver diseases. However, preliminary results in patients with multiple organ failure (MOF) and sepsis were disappointing, possibly because the number of applied MARS cycles was too low. To determine potential effects of prolonged MARS treatment in patients with postsurgical MOF we evaluated five postoperative patients with acute liver failure and septic multiple organ dysfunction in a retrospective observational study. MARS cycles (13.4±1.9) were applied during an average time period of 17.2±5.2 days. Fresh frozen plasma, thrombocyte units and blood units were transfused to maintain pre-MARS Quick values and thrombocyte counts, and to keep the hemoglobin concentration above 8 g/dl. Plasma bilirubin concentrations declined significantly during treatment. In contrast, ammonia concentration remained constant, and parameters of the clotting system (Quick value) did not get better or even worsened (partial thromboplastin time) despite significantly increasing the substitution frequency of coagulatory factors. Due to poor clotting, we observed significant bleeding complications during MARS therapy causing a simultaneous rise in the number of transfused blood units. All patients demonstrated persistent, severe abdominal infection during MARS therapy. After discontinuing MARS treatment because of insufficient efficiency, all patients died of progressive septic organ malfunction. Our preliminary findings do not support use of MARS in patients with postoperative hepatic failure and progressive septic multiple organ dysfunction, particularly if the septic focus cannot be eliminated. If MARS is still applied, special attention should be paid to simultaneous clotting disorders and bleeding complications. [ABSTRACT FROM AUTHOR]