Nonalcoholic steatohepatitis (NASH) is emerging worldwide because life-styles have changed to include much over-eating and less physical activity. The clinical and pathophysiological features of NASH are very different from those of HBV- and HCV-chronic liver diseases. The prognosis of NASH is worse among those with nonalcoholic fatty liver diseases (NAFLD), and some NASH patients show HCC with or without cirrhosis. In the present review we discuss fibrogenesis and the relationship between fibrosis and HCC occurrence in NASH to clarify the role of MMPs and TIMPs in both mechanisms. Previously we proposed MMP and TIMP expression in the multi-step occurrence of HCC from the literature based on viral-derived HCC. We introduce again these expressions during hepatocarcinogenesis and compare them to those in NASH-derived HCC, although the relationship with hepatic stem/progenitor cells (HPCs) invasion remains unknown. Signal transduction of MMPs and TIMPs is also discussed because it is valuable for the prevention and treatment of NASH and NASH-derived HCC.

Patients were discharged without any complications. The umbilical wounds were almost invisible 1 month after surgery. We believe that SILS, with some technical refinements, can be safely applied for distal pancreatectomy. Although the cosmetic benefits of single-incision laparoscopic distal pancreatectomy are obvious, several issues such as the extent of invasiveness, cost, indications, and learning curve need to be investigated.

IntroductionThe PINPOINT® Endoscopic Fluorescence Imaging System (Novadaq, Mississauga, Canada) allows surgeons to visualize the bile ducts during laparoscopic cholecystectomy. Surgeons can continue operation while confirming the bile ducts’ fluorescence with a bright‐field/color image. However, strong fluorescence of the liver can interfere with the surgery. Here, we investigated the optimal timing of indocyanine green administration to allow fluorescent cholangiography to be performed without interference from the liver fluorescence.MethodsA total of 72 patients who underwent laparoscopic cholecystectomy were included in this study. The timing of indocyanine green administration was set immediately before surgery and at 3, 6, 9, 12, 15, 18, and 24 h before surgery. The luminance intensity ratios of gallbladder/liver, cystic duct/liver, and common bile duct/liver were measured using the ImageJ software (National Institutes of Health, Bethesda, USA). Visibility of the gallbladder and bile ducts was classified into three categories (grades A, B, and C) based on the degree of visibility in contrast to the liver.ResultsThe luminance intensity ratio for the gallbladder/liver, cystic duct/liver, and common bile duct/liver was ≥1 in the 15‐, 18‐, and 24‐h groups. The proportion of cases in which evaluators classified the visibility of the gallbladder and bile ducts as grade A (best visibility) reached a peak in the 15‐h group and decreased thereafter.ConclusionsIn the present study, the optimal timing of indocyanine green administration for fluorescent cholangiography during laparoscopic cholecystectomy using the PINPOINT Endoscopic Fluorescence Imaging System was 15 h before surgery.

Background/AimsNonalcoholic steatohepatitis (NASH) is prevalent in both economically developed and developing countries. Twenty percent of NASH progresses to cirrhosis with/without hepatocellular carcinoma, and there is an urgent need to find biomarkers for early diagnosis and monitoring progression of the disease. Using immunohistochemical and immunoelectron microscopic examination we previously reported that expression of matrix metalloproteinase-1 (MMP-1) increased in monocytes, Kupffer cells and hepatic stellate cells in early stage NASH. The present study investigated whether serum MMP-1 levels reflect disease activity and pharmaceutical effects in NASH patients.MethodsWe measured the serum levels of MMPs, tissue inhibitors of metalloproteinases (TIMPs), and several cytokines/chemokines in patients with histologically proven early and advanced stages of NASH and compared them with those in healthy controls.ResultsSerum MMP-1 levels in stage 1 fibrosis, but not in the more advanced fibrosis stages, were significantly higher than in healthy controls (P=0.019). There was no correlation between serum MMP-1 level and fibrosis stage. Serum MMP- 1 levels in NASH patients represented disease activity estimated by serum aminotransferase values during the follow-up period. In contrast, MMP-2, MMP-9 and TIMPs did not change with disease activity. Consistent with the finding that MMP-1 is expressed predominantly in monocytes and Kupffer cells, serum levels of monocyte chemotactic protein-1 and granulocyte-colony stimulating factor were significantly increased in NASH with stage 1 fibrosis.ConclusionsThese results suggest that serum MMP-1 levels represent disease activity and may serve as a potential biomarker for monitoring the progression of NASH.