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Nutritional status and skeletal muscle mass affect the prognosis of hepatocellular carcinoma (HCC). Nutritional status is closely associated with skeletal muscle mass. Here, we investigate the effect of controlling preoperative nutritional status and skeletal muscle mass on the prognosis of HCC after curative treatment.This retrospective analysis contained 181 patients who received curative treatment of HCC including liver resection or radiofrequency ablation (RFA) therapy. Nutritional status and skeletal muscle mass were evaluated prior to therapy using the controlling nutritional status (CONUT) score and psoas muscle mass index (PMI), respectively. Associations of predictor variables with overall survival (OS) and progression-free survival (PFS) were determined using Cox proportional hazards regression and CHAID decision tree algorithm analysis.A total of 111 patients (61.3%) were determined to be of poor nutritional status and 100 patients (55.2%) had muscle mass depletion. Patients with PS 0, Barcelona clinic liver cancer (BCLC) stage 0, low CONUT score, and high PMI showed significantly better OS than those with PS 1, BCLC stage A, high CONUT score, and low PMI. Multivariate analysis indicated that a high CONUT score [hazard ratio (HR) 4.130; 95% confidence interval (CI), 1.713-9.958; P lt; 0.01) and low PMI (HR 4.625; 95% CI, 1.704-12.549; P lt; 0.01) found to be useful for predicting OS in patients after curative treatment of HCC. Regarding PFS, a significant predictor was only tumor numbers in univariate analysis (HR 2.147; 95% CI, 1.350-3.414; P = 0.001). In decision tree analysis, the mortality rate was 28.8%, 12.5%, and 1.9% in patients with a high CONUT score, with a low CONUT score-low PMI, or with a low CONUT score-high PMI, respectively.The combined CONUT score and PMI were found to be independent predictors of OS in HCC patients after liver resection or RFA.

Background Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non‐cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin. Methods This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast‐enhanced computed tomography (CE‐CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected. Results A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non‐formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT‐SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT‐SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment. Conclusions EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin‐containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture., We aimed to identify the characteristics of patients who developed esophagogastric varices (EGV) after treatment with oxaliplatin. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin‐containing chemotherapy, EGV should be confirmed by endoscopy for avoiding subsequent rupture.

Background:Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate; however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-chain amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition.Methods:The correlation between serum BA levels and psoas muscle mass index (PMI) was examined in 73 CLD patients. Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy.Results:In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist.Conclusions:Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival.Funding:This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115. Maintaining cirrhotic rats were partially supported by Otsuka Pharmaceutical Company.

Background Measurement of the tricuspid regurgitation pressure gradient (TRPG) by echocardiography is recommended as the most objective examination for the detection of portopulmonary hypertension (PoPH). This prospective study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a screening method for identifying patients most likely to benefit from investigation with echocardiography.Results Four hundreds and eighty-six patients with cirrhosis underwent Doppler echocardiography, and were analyzed in the present study. Of the 486 patients, 51 (10.5%) had TRPG ≥35 mmHg. The median BNP was 39.5 (range, 3.3–712.0) pg/mL. Ninety-one (18.7%) patients reported shortness of breath. Multivariate analysis identified female, shortness of breath, and BNP ≥49 pg/mL as independent factors for TRPG ≥35 mmHg. The risk score for predicting TRPG ≥35 mmHg was calculated: risk score = −3.230 + 0.622 × gender (female: 1, male: 0) + 1.403 × shortness of breath (presence: 1, absence: 0) + 0.726 × BNP (≥ 49pg/mL: 1, −8).Conclusions We clarified the characteristics of patients with suspected PoPH, and developed a scoring model for identifying patients at high risk of PoPH, which may have utility in selecting patients with cirrhosis that may benefit from echocardiography.

Rifaximin (RFX) treatment can attenuate not only hyperammonemia but also Enterococcus faecalis translocation and 10‐7G values, suggesting that RFX treatment may improve intestinal inflammation and result in better overall survival.

A 70-year-old man was diagnosed with hepatocellular carcinoma (HCC) with portal vein invasion and lung metastases, for which atezolizumab plus bevacizumab (ATZ/BEV) was initiated. After two months, computed tomography revealed tumor growth accompanied by ascites, right ventricular invasion, exacerbation of the lung metastases, and main portal vein invasion. However, continuation of ATZ/BEV caused remarkable size reductions in all lesions, finally resulting in the disappearance of the vascular invasion and lung metastases after nine cycles of treatment. The tumor growth was considered to reflect pseudoprogression, which is difficult to distinguish from hyperprogression. We herein report a remarkable HCC case of pseudoprogression on ATZ/BEV.

[Background & aims] Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate, however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition. [Methods] Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy. The correlation between serum BA levels and psoas muscle area index (PMI) was examined in 73 CLD patients. [Results] Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist. In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. [Conclusion] Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival. [Funding] This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115.

Objectives To identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function. Methods We selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS. Results Low value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence. Conclusions Patients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS.

Aim Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). Methods Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. Results Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. Conclusions Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.

Aim Clinical evaluations are generally used to verify the effectiveness of detoxification treatments for alcohol dependence, but new objective biomarkers are essential for accurate diagnosis. We aim to assess the accuracy of % carbohydrate-deficient transferrin (CDT) in a cohort of Japanese patients admitted to a psychiatric hospital specializing in alcohol dependence. In addition, we investigated the kinetics of %CDT during alcohol moderation or cessation. Methods The study cohort consisted of 126 alcohol-dependent patients. The levels of serum %CDT were assessed by the N Latex CDT direct immuno-nephelometric assay. Results Alcohol consumption was significantly correlated with %CDT. The only independent predictive factor of alcohol consumption was %CDT, with glutamyl transpeptidase (GGT) and albumin-bilirubin (ALBI) score proving insufficient. The cut-off value of %CDT was 1.9 % with high sensitivity and specificity in detecting alcohol abstinence beyond 30 days (68.6% sensitivity, 91.8% specificity) and excessive alcohol drinking (77.9% sensitivity, 77.1% specificity). %CDT levels were significantly decreased at 30-days of abstinence when compared with baseline. Notably, %CDT values were significantly changed even in the light alcohol drinking cohort (P = 0.0009), whereas GGT levels were not significantly changed. Conclusions Our results indicate that %CDT is an accurate and specific biomarker of alcohol consumption and is useful in detecting alcohol abstinence even in a low alcohol intake patient cohort. These results suggest that %CDT may be a useful objective biomarker of chronic alcohol abuse during clinical treatment for alcoholism. This article is protected by copyright. All rights reserved.

Background: The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of tolvaptan response in decompensated liver cirrhosis (LC) has started to attract more attention. Our aim is to elucidate predictive factors using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) that portend a good response to tolvaptan in LC patients with ascites.Methods: We enrolled 113 LC patients and divided into tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites and a follow-up assessment occurred after a 7-day tolvaptan treatment regimen. Results: We revealed predictive ability for kidney and/or liver damage in serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. Post 7-day tolvaptan treatment, 19 patients lost more than 1.5 kg of their body weight (Responders), while 19 patients did not change their body weight significantly (Non-responders). Basal blood urea nitrogen (BUN) (p=0.0014), serum copeptin (p=0.0265) and serum ZAG levels (p=0.0142) were significantly higher in the Non-responders. BUN (odds ratio 7.43, p=0.0306), copeptin (odds ratio 9.12, p=0.0136) and ZAG (odds ratio 7.43, p=0.0306) were determined to be predictive factors of drug responsiveness using multivariate logistic regression analysis.Conclusion: Serum BUN, copeptin and ZAG levels predict patient response to tolvaptan even when measured prior to treatment.

Aim The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with refractory ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of tolvaptan response in decompensated liver cirrhosis (LC) is also attracts attention. Our aim is to elucidate predictive factors using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) that portend a good response to tolvaptan in LC patients with ascites. Methods We enrolled 113 LC patients and divided into tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites and a follow-up assessment occurred after a 7-day tolvaptan treatment regimen. Results We revealed predictive ability for kidney and/or liver damage in serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. Post 7-day tolvaptan treatment, 19 patients lost more than 1.5 kg of their body weight (Responders), while 19 patients did not change their body weight significantly (Non-responders). Basal blood urea nitrogen (BUN) levels (p = 0.0014), serum copeptin (p = 0.0265) and serum ZAG levels (p = 0.0142) were significantly higher in the Non-responders. BUN (odds ratio 7.43, p = 0.0306), copeptin (odds ratio 9.12, p = 0.0136) and ZAG (odds ratio 7.43, p = 0.0306) were determined to be predictive factors of drug responsiveness using multivariate logistic regression analysis. Conclusion Serum BUN, copeptin and ZAG levels predict patient response to tolvaptan even when measured prior to treatment.

BACKGROUND AND AIM Copeptin is a stable cleavage product of the arginine vasopressin precursor and is equimolarly secreted with arginine vasopressin. We aimed to assess whether copeptin is the surrogate marker for complications related chronic liver disease (CLD) such as ascites, hepatic encephalopathy (HE), portosystemic shunts (PSSs), and all causes of mortality in CLD. METHODS Serum copeptin was measured in 170 CLD patients upon hospital admission. The association of copeptin levels with liver enzymes, liver functional reserve, and clinical parameters was investigated. Cox proportional hazard regression, logistic regression, and Kaplan-Meier analyses were performed to evaluate the associations of copeptin and ascites, HE and PSS formation, and prognostic factors with short-term (1 year) and long-term (4 years) mortality. RESULTS Serum copeptin levels were significantly correlated with liver and renal function, elevated in parallel with liver disease progression, and also associated with HE. Serum copeptin, albumin-bilirubin score and hepatocellular carcinoma were independent predictors of PSS formation and decreased rate of survival. Serum copeptin and albumin-bilirubin scores were independent predictors of ascites retention. The short-term and long-term cumulative mortality rate was significantly decreased in patients with serum copeptin >5.5 or >4.8 pmol/mL compared with patients in whom serum copeptin levels were

Aims Interferon-free direct-acting antiviral agent (DAA) regimens for chronic hepatitis C virus (HCV) patients have improved their health-related quality of life (HRQOL). Currently, there are no published data assessing the impact of DAAs regimens without sofosbuvir on HRQOL. The aim of this study was to investigate the improvement of HRQOL in Japanese HCV patients treated with a protease inhibitor and a nonstructural protein 5A inhibitor. Methods and Results A total of 123 Japanese genotype 1b HCV patients receiving daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks were enrolled. HRQOL was assessed using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ) at baseline; weeks 4, 12, and 24; and post-24 weeks. Changes in CLDQ scores were calculated by subtracting the CLDQ score at each time point from the baseline value. Improvement in the mean change of the Japanese version of the CLDQ score became statistically significant as early as week 4 after the initiation of treatment (+9.3%; P

Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre-existence of Y93 H resistance-associated variants (RAVs) in the non-structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post-treatment was possible. Pre-treatment RAVs in the non-structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)-Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR-Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1-25% in 5 patients, 26-75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of

Background/aims We compared the predictive abilities of the Abbott Real Time hepatitis C virus (HCV) assay (ART) with those of standard serum HCV ribonucleic acid (RNA) detection methods in patients undergoing triple therapy, which involves treatment with a protease inhibitor combined with pegylated interferon and ribavirin. Materials and methods In this study, 28 patients underwent triple therapy. The hepatitis C virus ribonucleic acid (HCV RNA) level of each patient was measured at weeks 0, 4, 8, and 12 after the initiation of therapy using the Roche COBAS AmpliPrep/COBAS TaqMan HCV assay version 1.0 (CAP/CTM v1.0) and ART. Results At week 8 after the initiation of therapy, the sustained virological response (SVR) rate among patients who tested negative and positive for HCV RNA using CAP/CTM v1.0, was 80.0% (20/25) and 33.3% (1/3), and using ART, it was 91.3% (21/23) and 0.0% (0/5), respectively. Although at week 8, the predictive capability of CAP/CTM v1.0 was 78.5%, ART was found to be a more accurate predictor of future SVR status with a rate of 92.9%. Conclusion These results indicate that the presence or absence of serum HCV RNA, evaluated using ART at week 8 after the initiation of therapy, may be useful for predicting therapeutic outcomes in patients receiving triple therapy.

BackgroundCopper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib.MethodsWe enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy.ResultsThe serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratioConclusionsThe Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.

Oxaliplatin, a chemotherapeutic agent for colorectal cancer, has been associated with pathological evidence of sinusoidal endothelial injury in the liver. However, esophagogastric varices are a poorly recognized outcome of oxaliplatin-based chemotherapy. We report a 78-year-old man, whose past history of colon cancer was resection and treatment with mFOLFOX6 for 20 weeks, as adjuvant chemotherapy. After 3.5-year follow-up of the oxaliplatin-based chemotherapy, he was diagnosed with esophageal varices without liver dysfunction, indicating that the hepatotoxicity caused by oxaliplatin could be prolonged after its administration. Patients who have received oxaliplatin-based chemotherapy should be followed up carefully over the long term.

Fusobacterium nucleatum is an invasive, adherent, and pro-inflammatory anaerobic bacterium involved in various infections and colorectal cancer. We report a case with pyogenic liver abscess, diagnosed with advanced sigmoid colon cancer, in whom F. nucleatum was simultaneously detected. In this patient, F. nucleatum was systematically analyzed using the molecular biological techniques of metagenome analysis, conventional PCR, and microbial fluorescence in situ hybridization.

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus with the capabilities of tumorigenesis. We present an HCV-infected patient affected with B-cell lymphomas after suffering from hepatocellular carcinoma. The patient exhibited curative effects for lymphomas after treatment with sofosbuvir and ledipasvir, which is shown clearly with a positron emission tomography scanner.

Aims: The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C). Methods: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results: In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

Background/Aims: To evaluate the usefulness and safety of treating disseminated intravascular coagulation (DIC) compli-cating cholangitis primarily with antithrombin (AT) and throm-bomodulin (rTM). Methods: A DIC treatment algorithm was determined on the basis of plasma AT III levels at the time of DIC diagnosis and DIC score changes on treatment day 3. Laboratory data and DIC scores were assessed prospec-tively at 2-day intervals. Results: DIC reversal rates >75% were attained on day 7. In the DIC reversal group, statistically significant differences from baseline were observed in inter-leukin-6 and C-reactive protein levels within 5 days. Patients with no DIC score improvements after treatment with AT alone experienced slow improvement on a subsequent com-bination therapy with rTM. Although a subgroup with biliary drainage showed greater improvement in DIC scores than did the nondrainage subgroup, the mean DIC score showed improvement even in the nondrainage subgroup alone. Gas-tric cancer bleeding that was treated conservatively occurred in one patient. As for day 28 outcomes, three patients died from concurrent malignancies. Conclusions: Although this algorithm was found to be useful and safe for DIC patients with cholangitis, it may be better to administer rTM and AT si-multaneously from day 1 if the plasma AT III level is less than 70%. (Gut Liver 2013;7:363-370)Key Words: Disseminated intravascular coagulation; Cholan-gitis; Antithrombins; ThrombomodulinINTRODUCTION

Purpose: The goal of this work was to develop a method of calculating blood flow and xenon solubility coefficient (λ) in the hepatic tissue by xenon-enhanced computed tomography (Xe-CT) and to demonstrate λ can be used as a measure of fat content in the human liver. Methods: A new blood supply model is introduced which incorporates both arterial blood and portal venous blood which join and together flow into hepatic tissue. We applied Fickˈs law to the model. It was theoretically derived that the time course of xenon concentration in the inflow blood (the mixture of the arterial blood and the portal venous blood) can be approximated by a monoexponential function. This approximation made it possible to obtain the time-course change rate (KI) of xenon concentration in the inflow blood using the time course of xenon concentration in the hepatic tissue by applying the algorithm we had reported previously. KI was used to calculate blood flow and λ for each pixel in the CT image of the liver. Twenty-six patients (49.2 ± 18.3 years) with nonalcoholic steatohepatitis underwent Xe-CT abdominal studies and liver biopsies. Steatosis of the liver was evaluated using the biopsy specimen and its severity was divided into ten grades according to the fat deposition percentage [(severity 1) ⩽ 10%, 10 %

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre-existence of Y93 H resistance-associated variants (RAVs) in the non-structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post-treatment was possible. Pre-treatment RAVs in the non-structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)-Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR-Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1-25% in 5 patients, 26-75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of1%, 1-25%, 26-75%, and ≥76% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (P 0.0001). The dominancy of pre-treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct-acting antiviral agent treatments. J. Med. Virol. 89:99-105, 2017. © 2016 Wiley Periodicals, Inc.

We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess.

A 66-year-old female patient with acute myeloid leukemia underwent remission-induction therapy and allogeneic peripheralstem cell transplantation. The patient was found to have a resolved hepatitis B virus (HBV) infection, as shown by her positivityfor the hepatitis B surface (HBs) antibody and hepatitis B core antibody and negativity for the HBs antigen and HBV-DNA. Administration of an immunosuppressant was started after transplantation for the prevention of graft-versus-host disease (GVHD), and hepatic impairment developed four months after transplantation. No changes were observed in serum HBV-related markerlevels, and a liver biopsy revealed GVHD. The course of hepatic impairment was followed up with the diagnosis of liverGVHD, without determining the level of HBV-related markers. Hepatic impairment recurred 13 months after transplantation. Determination of the HBV-related markers showed that the patient was positive for the HBs antigen and HBV-DNA. The patientwas diagnosed as having de novo hepatitis B, and the hepatitis improved after the start of anti-viral therapy. In administering immunosuppressive therapy and chemotherapy for patients with a resolved HBV infection, it is important to test for viral markersregularly by paying constant attention to the possible onset of de novo hepatitis B, despite the existing hepatic disease.