Akio Moriya

Alcohol consumption appears to protect against non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2011; 33: 378–388

Roles of alcohol consumption in fatty liver: A longitudinal study

BACKGROUND & AIMS Roles of alcohol consumption in non-alcoholic fatty liver disease are still controversial, although several cross-sectional studies have suggested the beneficial effect of light to moderate drinking on fatty liver. We analyzed the longitudinal relationship between drinking pattern and fatty liver. METHODS We included 5297 Japanese individuals (3773 men and 1524 women) who underwent a baseline study in 2003 and follow-up at least once from 2004 to 2006. Generalized estimating equation was used to estimate any association between drinking pattern and fatty liver assessed by ultrasonography. RESULTS At baseline, 1179 men (31.2%) and 235 women (15.4%) had fatty liver; 2802 men (74.2%) and 436 women (28.6%) reported alcohol consumption. At the latest follow-up, 348 of 2594 men (13.4%) and 101 of 1289 women (7.8%) had newly developed fatty liver; 285 of 1179 men (24.2%) and 70 of 235 women (29.8%) demonstrated a remission of fatty liver. In men, drinking 0.1-69.9 g/week (odds ratio, 0.79 [95% confidence interval, 0.68-0.90]), drinking 70.0-139.9 g/week (0.73 [0.63-0.84]), drinking 140.0-279.9 g/week (0.69 [0.60-0.79]), and drinking ⩾280.0 g/week (0.68 [0.58-0.79]) were inversely associated with fatty liver after adjusting for obesity, exercise, and smoking. In women, drinking 0.1-69.9 g/week (0.71 [0.52-0.96]) and drinking 70.0-139.9 g/week (0.67 [0.45-0.98]) were inversely associated with fatty liver after the adjustment. CONCLUSIONS Light to moderate alcohol consumption, or even somewhat excessive amounts especially in men, was likely to protect most individuals against fatty liver over time.

Long-term monitoring of platelet count, as a non-invasive marker of hepatic fibrosis progression and/or regression in patients with chronic hepatitis C after interferon therapy.

Background:  Platelet count has been shown to correlate with the hepatic fibrosis stage in chronic hepatitis C (CHC). The aim of the present study was to assess hepatic fibrosis progression or regression of CHC patients by long‐term monitoring of the platelet count.

Intrahepatic mRNA levels of type I interferon receptor and interferon-stimulated genes in genotype 1b chronic hepatitis C. Association between IFNAR1 mRNA level and sustained response to interferon therapy.

Objective: The aim of this study was to determine the association between pretreatment intrahepatic mRNA levels of interferon receptor and interferon-stimulated genes and response to interferon therapy for genotype 1b chronic hepatitis C. Methods: Forty-four patients with genotype 1b chronic hepatitis C who underwent liver biopsy and then received interferon therapy participated in this study. Pretreatment intrahepatic mRNA levels of interferon receptor genes (IFNAR1, IFNAR2b, and IFNAR2c) and interferon-stimulated genes (OAS1 and PKR) were quantified by competitive polymerase chain reaction. Results: In the genes examined, only IFNAR1 mRNA level was significantly higher in patients with sustained virological and biochemical response to interferon therapy versus those with nonsustained response (p < 0.01). Moreover, mRNA expression ratios of IFNAR1 to IFNAR2 were also significantly higher in patients with sustained virological and biochemical response to IFN therapy (p < 0.01 and p < 0.05, respectively). On the other hand, mRNA levels of IFNAR2b, IFNAR2c, and PKR were significantly higher in patients with histologically active or advanced liver rather than patients with mild or less advanced liver. Conclusions: High intrahepatic mRNA levels of IFNAR1 and mRNA ratio of IFNAR1 to IFNAR2 before treatment may be associated with a favorable response to interferon therapy.

Hepatitis B Virus Gene in Liver Tissue Promotes Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients

The hepatitis B virus (HBV) gene has been detected in hepatocellular carcinoma (HCC) tissue negative for the hepatitis B surface antigen and positive for the hepatitis C virus (HCV) antibody, but the precise role of the HBV gene in hepatocarcinogenesis has yet to be clarified. We studied the HBV gene in liver tissue several years before the emergence of HCC. Eleven patients diagnosed with HCV-positive chronic liver disease and who developed HCC were assigned to group A. HBV DNA was detected in 8 of the 11 patients (73%). Twenty-five patients, who did not develop HCC, were selected as group B. Six of the group B patients were classified as DNA-positive (24%). The HBV DNA in liver tissue was found to be significantly related to HCC development (P < 0.01). Thus, the presence of the HBV gene in patients with chronic HCV associated-liver injury appears to promote hepatocarcinogenesis, although prospective studies are needed to confirm this result.

A target-controlled infusion system with bispectral index monitoring of propofol sedation during endoscopic submucosal dissection

Background and study aims: Propofol administration via a target-controlled infusion system with bispectral index monitoring (BIS/TCI system) is expected to prevent complications from sedation during complex and long endoscopic procedures. We evaluated the feasibility of setting the BIS/TCI system for non-anesthesiologist administration of propofol (NAAP) during endoscopic submucosal dissection (ESD). Patients and methods: From May 2009 to February 2013, 250 patients with esophagogastric neoplasms were treated with ESD using the BIS/TCI system with NAAP. In the TCI system, the initial target blood concentration of propofol was set at 1.2 μg/mL. The titration speed of propofol was adjusted according to the BIS score and the movement of the patient. The BIS target level ranged from moderate to deep sedation, at which a stable BIS score between 60 and 80 was obtained. Results: In 80.4 % of patients, it was possible to maintain stable sedation with a blood concentration of propofol of less than 1.6 µg/mL using TCI throughout the ESD procedure. The default setting for ideal blood concentration of propofol was 1.2 μg/mL, because the medians of the lower and upper bounds of blood concentration were 1.2 μg/mL (range 0.6 – 1.8 μg/mL) and 1.4 μg/mL (range 1.0 – 3.8 μg/mL), respectively. Although hypotension occurred in 27 patients (10.8 %), oxygen desaturation occurred in only nine patients (3.6 %), and severe desaturation in only two patients (0.8 %). Conclusions: Using our settings, it is possible for a non-anesthesiologist to maintain stable sedation during a lengthy endoscopic procedure through propofol sedation with a BIS/TCI system.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

Objective: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. Methods: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. Results: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). Conclusion: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan

BackgroundThe real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1.MethodsThe rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics.ResultsOverall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment.ConclusionsThe EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.

854 IMPACT OF ALCOHOL CONSUMPTION ON THE PRESENCE, DEVELOPMENT, AND IMPROVEMENT OF FATTY LIVER IN MEN AND WOMEN

854 IMPACT OF ALCOHOL CONSUMPTION ON THE PRESENCE, DEVELOPMENT, AND IMPROVEMENT OF FATTY LIVER IN MEN AND WOMEN A. Moriya, Y. Iwasaki, S. Ohguchi, E. Kayashima, T. Mitsumune, H. Taniguchi, F. Ikeda, K. Yamamoto. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Junpukai Health Maintenance Center, Okayama, Japan E-mail: moriyaakio@gmail.com

P1016 : Factors associated with the development of fatty liver or glucose intolerance

measuring different quantities and so bias cannot be assessed directly. The recently cleared (FDA, CE Mark, and TGA) HepaFatScan MRI method reports a volumetric fraction of liver tissue that is fat, a measure that can be directly compared with measurements from biopsy histological sections. This study measures the degree of bias of the HepaFat-Scan method against unbiased stereological measurements from biopsies. Stereological analysis (SA) is a method of obtaining unbiased estimates of volume fractions of a phase of material in a 3D matrix from a cross section through the matrix. Methods: Volumetric fractions of fat in liver tissue of 59 patients (autoimmune hepatitis 3, alcoholic liver disease 2, viral hepatitis 16, NAFLD 10, NASH 17, normal 3, primary sclerosing cholangitis 4, other 4) recruited from the hepatology outpatient clinics at Fremantle and Sir Charles Gairdner Hospitals (Western Australia) were measured by SA of digital images of histological sections of liver biopsies and with non-invasive HepaFat-Scan measurements. Bland–Altman (BA) statistics were used to assess the bias between the two methods of measurement. A steatosis grade for each biopsy was also assessed by an experienced hepatopathologist. ROC curve analysis was used to determine sensitivity and specificity of HepaFat-Scan for predicting steatosis grade. Results: Figure 1 shows a plot of the volumetric fraction of fat measured by HepaFat-Scan plotted against that measured by SA of biopsy histological sections. The straight line is the line of equivalence (not a fitted regression line). BA analysis indicates a small systematic bias with HepaFat-Scan reporting volumetric liver fat fractions 1.4% higher than SA of biopsy. Sensitivities, specificities and areas under ROC curve for HepaFat-Scan predicting steatosis grade >0 were 97%, 96%, and 0.963; >1 were 100%, 94%, and 0.996; and >2 were 100%, 88%, and 0.971. Conclusions: The 1.4% bias between HepaFat-Scan and SA of biopsy is not clinically significant since it represents less than 5% of the overall range of fat fractions measured. The observed high sensitivities and specificities indicate that overall accuracy of HepaFat-Scan is sufficient for clinical patient management.