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Hepatocyte growth factor (HGF) has various effects especially on epithelial cells. However, the precise role of HGF on lipogenesis is still not fully understood. A high-fat diet was administered to HGF transgenic mice and wild-type control mice in vivo. Furthermore, recombinant human HOE (rhHGF) was administered to HepG2 cell line in vitro. We performed an analysis regarding the factors relating to lipid metabolism. An overexpression of HGF dramatically ameliorates a high-fat diet-induced fatty liver. HGF transgenic mice showed an apparently reduced lipid accumulation in the liver. The activation of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (ApoB) accompanying higher triglyceride levels in the serum were found in HGF transgenic mice on a normal diet. Interestingly, this upregulation of the MTP activation became more apparent in the high-fat diet. In addition, the administration of rhHGF stimulated MTP and ApoB expression while reducing reduced the intracellular lipid content in HepG2 cell line. However, this induction of MTP and ApoB by HOF was clearly inhibited by PD98059 (MAPK inhibitor). In conclusion, the data presented in this study indicated that HGF ameliorates a high-fat diet-induced fatty liver via the activation of MTP and ApoB. [ABSTRACT FROM AUTHOR]

Adult onset type II citrullinemia (CTLN2) is an autosomal recessive disease accompanied with hyperammonemia and a sudden onset of psychiatric disorders. We demonstrated three male patients with CTLN2 having a liver histology of non-alcoholic steatohepatitis (NASH). Patients with NASH were analyzed for the causative gene of CTLN2, SLC25A13 and discussed. [Copyright &y& Elsevier]

Background: The incidence of acute hepatitis A infection in Japan peaked 10 years ago and has been decreasing since then. However, an increase in severe cases of the disease has been documented recently. We experienced an outbreak in 1998–1999, and compared the clinical features of the disease in 1998–1999 (recent outbreak) and in 1987–1988 (past outbreak) in our prefecture (Gunma). Methods: Forty patients with acute hepatitis A were admitted to nine Gunma hospitals from October 1998 to September 1999. Their clinical features were compared with those of 100 patients with acute hepatitis A admitted to the same hospitals in 1987–1988. Results: Both outbreaks occurred mostly during the winter-spring season. Secondary familial infection was significantly decreased in the recent outbreak. Patients in the recent outbreak were 7 years older than those in the past outbreak. Laboratory findings, such as serum aspartatate aminotransferase (AST) and alanine aminotransferase (ALT) levels and prothrombin time, were worse in the recent than in the past outbreak. Severe-type hepatitis and fulminant hepatitis occurred in 5 patients (12.5%) in the recent outbreak but in only 2 patients (2.0%) in the past outbreak. Conclusions: Clinical data and manifestations were more severe in the recent outbreak than in the past outbreak of acute hepatitis A. It is important to be aware of hepatitis A virus infection and to take into account the available vaccination against hepatitis A virus in Japan. [ABSTRACT FROM AUTHOR]

The UDP-glucuronosyltransferase UGT1A1 plays a critical role in the detoxification of potentially neurotoxic bilirubin by conjugating it with glucuronic acid. We identified a polymorphism that results in a T to G substitution at nucleotide number −3263 of the phenobarbital-responsive enhancer module of the UGT1A1 gene, thereby significantly decreasing transcriptional activity as indicated by the luciferase-reporter assay. At least one T-3263G allele was found in 21 of 25 subjects with mild hyperbilirubinemia (Gilbert''s syndrome); this frequency (0.58) was significantly higher than that in normobilirubinemic controls (0.17; n = 8 of 27). Homozygous mutations in the TATA element (A[TA]7TAA) or at nucleotide 211 of exon 1 (G to A substitution) were found in 5 and 2 of the hyperbilirubinemic group, respectively, while 12 of these subjects were double heterozygotes for the T-3263G and G211A mutations. Plasma total bilirubin levels in these double heterozygotes were significantly higher than those in control subjects carrying one or other of these mutations singly, indicating that compound heterozygous mutations may result in more strongly reduced UGT1A1 activity. Our results indicate that homozygosity and compound heterozygosity for mutations in the UGT1A1 gene promoter (T-3263G and A[TA]7TAA) and/or exon 1 of the gene (G211A) could explain the hyperbilirubinemia seen in the majority of individuals with Gilbert''s syndrome. [Copyright &y& Elsevier]

A 14-year-old girl with blood type B with late onset hepatic failure (LOHF) of unknown cause has survived through living-related liver transplantation (LRLT). No hepatitis virus, including HAV, HBV, HCV, and HGV, was positive at the onset of LOHF. Autoimmune hepatitis was thought to be the cause because of positive results for serum anti-nuclear antibody at 80 times dilution and elevated gamma-globulin, but treatment with glucocorticoid did not suppress the progressive hepatic failure. Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure. She was treated by repeated plasmapheresis and plasma absorption for 10 months, and then received the left lobe of her mother's liver. (Her mother's blood type was AB). The patient had been well, being treated with tacrolimus and prednisolone, although the serum titer of anti-blood type B antibody was high just after LRLT and mild liver dysfunction continued for more than 3 years after LRLT. Follow-up biopsy 3 years after LRLT revealed chronic hepatitis and progression to liver cirrhosis. Re-transplantation is now under consideration; the patient is now aged 19 years. [ABSTRACT FROM AUTHOR]

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-β twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25–67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-β. Three million units (MU) of IFN-β was administered twice daily every day for 4 weeks followed by 10 MU of IFN-α2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-β, 148 MU; IFN-α2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor® assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml–1 (1 MEq ml–1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml–1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml–1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-β. The combination of twice-daily administration of IFN-β for 4 weeks followed by IFN-α showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low.... [ABSTRACT FROM AUTHOR]

Background: We compared clinical outcomes of carbon ion radiotherapy and transarterial chemoembolization in the treatment of hepatocellular carcinoma.Methods: Data of 477 patients with hepatocellular carcinoma who had undergone carbon ion radiotherapy or transarterial chemoembolization between April 2007 and September 2016 were retrospectively reviewed. Treatment naïve patients with single HCC, who underwent carbon ion radiotherapy or transarterial chemoembolization as a primary treatment were included. Clinical outcomes of the treatments were compared after utilizing propensity score matching.Results: Of 124 patients who received carbon ion radiotherapy and 353 patients who received transarterial chemoembolization, 31 and 23 patients met our inclusion criteria, respectively. After utilizing propensity score matching, 17 matched pairs of patients from each treatment group were analyzed. The median follow-up durations after carbon ion radiotherapy and transarterial chemoembolization were 43 and 32 months, respectively. The 3-year overall survival, local control, and progression-free survival rates in the carbon ion radiotherapy versus transarterial chemoembolization groups were 88% versus 58% (p < 0.05), 80% versus 26% (p < 0.01), and 51% versus 15% (p < 0.05), respectively.Conclusions: Carbon ion radiotherapy showed more favorable clinical outcomes than did transarterial chemoembolization for patients with single hepatocellular carcinoma after matching patient characteristics utilizing propensity score matching. Further studies with larger patient numbers are required to confirm our results.Trial Registration: UMIN000036455 : date of registration 22 March 2019, retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: To evaluate the safety and efficacy of carbon ion radiotherapy (C-ion RT) for 80 years or older patients with hepatocellular carcinoma (HCC).Methods: Eligibility criteria of this retrospective study were: 1) HCC confirmed by histology or typical hallmarks of HCC by imaging techniques of four-phase multidetector-row computed tomography or dynamic contrast-enhanced magnetic resonance imaging; 2) no intrahepatic metastasis or distant metastasis; 3) no findings suggesting direct infiltration of the gastrointestinal tract; 4) performance status ≤2 by Eastern Cooperative Oncology Group classification; and 5) Child-Pugh classification A or B. Patients received C-ion RT with 52.8 Gy (RBE) or 60.0 Gy (RBE) in four fractions for usual cases and 60.0 Gy (RBE) in 12 fractions for close-to-gastrointestinal tract cases. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0).Results: Between March 2011 and November 2015, 31 patients were treated. The median follow-up period of all patients was 23.2 months (range: 8.4-55.3 months). Median age at the time of registration of C-ion RT was 83 years (range: 80-95 years). Child-Pugh grade A and B were 27 patients and 4 patients, respectively. The 2-year estimated overall survival, local control, and progression-free survival rates were 82.3%, 89.2%, and 51.3%, respectively. No patients had Grade 2 or higher acute toxicities (within 3 months after C-ion RT). One patient experienced progression in Child-Pugh classification from A to B within 3 months after C-ion RT. In late toxicities, Grade 3 encephalopathy was observed in 3 patients, and 2 improved with medication.Conclusions: C-ion RT was effective with minimal toxicities for 80 years or older patients with hepatocellular carcinoma.Trial Registration: UMIN000020571 : date of registration, 14 January 2016, retrospectively registered. [ABSTRACT FROM AUTHOR]