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AIM Sarcopenia has a high prevalence and can be an adverse predictor in patients with chronic liver diseases (CLDs). We sought to assess the prevalence of sarcopenia and its prognostic significance in patients with CLDs at multiple centers in Japan. METHODS In this retrospective study, we collated the data of 1624 patients with CLDs (976 men). The diagnosis of sarcopenia was determined by the sarcopenia assessment criteria of the Japan Society of Hepatology. Predictors of mortality were identified using univariate and multivariate analyses. RESULTS Muscle weakness and skeletal muscle loss occurred in 33.5% and 29.3% of all subjects, respectively, while sarcopenia occurred in 13.9% of all patients. Patients with sarcopenia had a poorer prognosis among all patients, patients with hepatocellular carcinoma (HCC), and those without HCC by log-rank test. The multivariate Cox proportional hazards model identified female gender (hazard ratio [HR], 0.59; p = 0.03), alcoholic liver disease (HR, 4.25; p

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

AIM Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically. METHODS A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically. RESULTS The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p

High‐level synthesis (HLS), which automatically synthesizes a register‐transfer level (RTL) circuit from a behavioral description written in a high‐level programming language such as C/C++, is becoming a more popular technique for improving design productivity. In general, HLS tools often generate a circuit with a larger area than those of hand‐designed ones. One reason for this issue is that HLS tools often generate multiple instances of the same module from a function. To eliminate such a redundancy in circuit area in HLS, HLS tools are capable of sharing modules. Function‐level module sharing at a behavioral description written in a high‐level programming language may promote function reuse to increase effectiveness and reduce circuit area. In this paper, we present two HLS techniques for module sharing at the function level.

AIM We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all

AIM Transient elastography (TE) is the gold standard for measurement of liver stiffness. The usefulness of shear wave elastographies (SWE) is well accepted. However, the measurement values cannot be equivalently compared because cut-off values for the diagnosis of liver fibrosis are different among those devices. We aimed to clarify correlations, to generate the regression equations between TE and SWEs, and to compare the diagnostic ability of each device to diagnose liver fibrosis. METHODS A total of 109 patients with chronic liver disease who underwent liver biopsy and same-day evaluation of liver stiffness using six ultrasound devices were analyzed. The diagnostic ability of liver stiffness from each ultrasound device and correlations between TE and each SWE were analyzed. RESULTS Liver stiffness measured by all six ultrasound devices increased significantly as liver fibrosis stage advanced (P

AIM We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy. METHODS Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n = 57), and those who received previous NA therapy were assigned to the validation cohort (n = 69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA levels was constructed. Next, the reproducibility of that formula was assessed. RESULTS In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P = 0.0227), hepatitis B e antigen (HBeAg) (P = 0.0067) and log10 (HB surface antigen [HBsAg]) (P = 0.0497) were significant, whereas HB core-related antigen (HBcrAg) tended to be significant (P = 0.0562). The formula was constructed and named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg, and HBsAg). The FBS-cres score was calculated as: 3.1686 - (0.0148 × FBS) + (0.1982 × HBcrAg) + (0.0008168 × HBeAg) + (0.1761 × log10 (HBsAg)). In the training cohort, a significant correlation was noted between HBcrAg and IH-cccDNA levels (P

BACKGROUND Although the mumps vaccine has not been included in the national immunization program (NIP) in Japan, it has been shown that a two-dose routine vaccine program would be highly cost-effective. In this study, we carried outa questionnaire-based study to investigate how many Japanese parents want the mumps vaccine to be included in the NIP with proper information. METHODS The questionnaire was given to parents who visited the Pediatrics or neonatal intensive care unit of Nara Prefecture General Medical Center, Nara City, Japan, between 1 March 2017 and 31 August 2017. The questionnaire consisted of information about mumps and six questions, for example (i) do parents know that mumps can be prevented by vaccine; (ii) do they know that they need to pay for mumps vaccines; and (iii) do they hope that the government will resume routine mumps vaccination. RESULTS In total, 1,224 parents answered the questionnaire. A total of 81% and 75.4% of parents knew that mumps can be prevented by vaccination and that mumps vaccine is not included in the NIP, respectively, before reading the information. After reading the information, 95.0% of parents thought that mumps vaccine should be included in the NIP. While 61.7% of parents answered that they would choose two-dose vaccination without governmental financial support, 92.1% of them would choose two-dose vaccination with governmental financial support (P < 0.0001). CONCLUSION Japanese parents want the mumps vaccine to be included in the NIP. Japan is able to start routine use of the mumps vaccine now.

Background We aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC). Methods A total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm2/m2). The study cohort was divided into two groups based on the median myostatin value in each gender. Results Our study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4–12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4–8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child–Pugh A patients (n = 123) was 2726.0 pg/mL (578.4–12667.2 pg/mL), whereas that for Child–Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3–12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1-, 3-, 5-, and 7-year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high-myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low-myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1-, 3-, 5-, and 7-year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high-myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low-myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (P

Aims To develop and validate a simple predictive model using easily obtained clinical parameters to predict decreased skeletal muscle mass (DSMM) in chronic liver disease (CLD) patients (n = 652). Methods Study subjects were divided into a training set (n = 326) and a validation set (n = 326). DSMM was diagnosed based on skeletal muscle mass index measured by bioimpedance analysis. Variables significantly associated with DSMM were identified using univariate and multivariate analyses in the training set and used to construct a predictive formula. Receiver operating characteristic (ROC) curve analysis was performed and the predictive model was validated in the validation set. Subgroup analyses were performed based on gender, age or cirrhosis status of patients. Results Body mass index (BMI), age, serum albumin and branched-chain amino acid to tyrosine ratio (BTR) were determined to be significant predictive factors for DSMM. A composite formula “BALB score” was constructed [-7.740 + (0.539 × BMI) + (-0.112 × Age) + (1.358 × Albumin) + (-0.264 × BTR)]. BALB score had the best predictive characteristics among all variables in both population sets (Area under the ROC curve; 0.877-0.898). Patients with DSMM were stratified into three BALB score categories (>4, 0-4, and

Aims To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). Methods A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis. Results Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients. Conclusion In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM.

Sarcopenia is defined by muscle loss and muscle dysfunction. Sarcopenia is classified into primary and secondary types, based on the cause. Primary sarcopenia is mainly aging-related sarcopenia, whereas secondary sarcopenia is the reduced muscle mass and strength that accompanies an underlying disease. Given the essential role of the liver in metabolism, secondary sarcopenia due to nutritional disorders or other factors can frequently occur in liver disease. In 2015, the Japan Society of Hepatology (JSH) decided to establish its own assessment criteria for sarcopenia in liver disease because the number of liver disease patients with sarcopenia is expected to increase and there is cumulative evidence to indicate sarcopenic patients have poor clinical outcomes. A working group to create assessment criteria for sarcopenia has thus been established by the JSH. In this article, we summarize the current knowledge with regard to sarcopenia and present the assessment criteria for sarcopenia in liver disease proposed by the JSH (1st edition). To the best of our knowledge, this is globally the first proposed assessment criteria for sarcopenia specializing in liver disease.

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P

Aim To examine the impact of pretreatment Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level on hepatitis B e-antigen (HBeAg) loss or HBeAg seroconversion (SC) for patients with nucleoside/nucleotide analog (NUC) therapy naive HBeAg positive chronic hepatitis B (CHB). Methods A total of 57 patients were analyzed. All subjects were initially treated with NUC. We examined the impact of pretreatment WFA+ -M2BP level on HBeAg loss and HBeAg SC using univariate and multivariate analyses. Results There were 36 men and 21 women (median age, 39 years). The WFA+ -M2BP cut-off index (COI) level ranged 0.43-12.9 (median, 1.55). WFA+ -M2BP level in patients with F3 or F4 was significantly higher than that with F0-F2. WFA+ -M2BP level in patients with A2 or 3 was significantly higher than that with A0 or 1. For all cases, the 1- and 3-year cumulative HBeAg loss rates were 10.5% and 34.4% and the corresponding cumulative HBeAg SC rates were 8.8% and 29.0%, respectively. In the multivariate analysis, in terms of HBeAg loss, pretreatment HBV DNA of 5 log copies/mL or more and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be significant factors linked to loss of HBeAg, while in terms of HBeAg SC, pretreatment HBV DNA of 5 log copies/mL or more was an independent predictor and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be a significant factor. Conclusion Pretreatment WFA+ -M2BP level may be a useful predictor for HBeAg loss or SC after NUC therapy for patients with HBeAg positive CHB.

Aim We aimed to construct a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) level in patients with chronic hepatitis C (CHC) and to validate its accuracy in an independent cohort. Methods A total of 386 patients with CHC were retrospectively analyzed. For the purpose of this study, we formed a training set (n = 210) and a validation set (n = 176). In the training set, we investigated variables linked to the presence of advanced fibrosis using univariate and multivariate analyses. We constructed a formula for predicting advanced fibrosis and validated its accuracy in the validation cohort. Receiver operating characteristic curve (ROC) analysis was carried out for calculating the area under the ROC (AUROC). Results In multivariate analyses, WFA+-M2BP (P = 0.029) and prothrombin time (PT) (P = 0.018) were found to be significant predictive factors linked to the presence of advanced fibrosis; platelet count (P = 0.098) and hyaluronic acid (P = 0.078) showed borderline statistical significance for the presence of advanced fibrosis. Using these four variables (with the initials MPPH), we constructed the following formula: MPPH score = −3.584 − (0.275 × WFA+-M2BP) + (0.068 × platelet count) + (0.042 × PT) − (0.005 × hyaluronic acid). In the training and validation sets, MPPH score yielded the highest AUROCs (0.87 and 0.83) for predicting advanced fibrosis among eight serum liver fibrosis markers. Similarly, in the training and validation sets, MPPH score had the highest diagnostic accuracies for predicting advanced fibrosis among eight serum variables (81.4% and 74.4%). Conclusion Our proposed MPPH scoring system can be useful for predicting advanced fibrosis in patients with CHC.

Aim To examine the relationship between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) levels and liver histological findings for patients with treatment naive chronic hepatitis B (CHB). Methods A total of 189 treatment naive-CHB patients were analyzed. We examined the effect of pretreatment serum WFA+-M2BP levels on histological findings compared with other laboratory markers, including aspartate aminotransferase (AST) to platelet ratio index, Fibrosis-4 index, platelet count, AST to alanine aminotransferase (ALT) ratio, and hyaluronic acid as liver fibrosis markers, and AST value, ALT value, and serum interferon-γ-inducible protein-10 level as liver inflammation markers. Results The WFA+-M2BP value ranged from 0.3 cut-off index (COI) to 12.9 COI (median value, 1.2 COI). The degree of liver fibrosis was significantly stratified according to WFA+-M2BP level in each group except for groups F2 and F3 and the degree of liver inflammation activity was significantly stratified according to WFA+-M2BP level in each group. For predicting F4, WFA+-M2BP level yielded the highest area under the receiver operating characteristic curve (AUROC) with a level of 0.87 and for predicting advanced liver fibrosis (≥F3) and significant liver fibrosis (≥F2), WFA+-M2BP level yielded the second highest AUROCs (both, 0.77) among six fibrotic markers. For predicting severe (A3) or significant liver inflammation activity (≥A2), AUROCs of WFA+-M2BP level were 0.78 and 0.76. Conclusion The WFA+-M2BP level can be a useful marker for assessing liver histological findings in patients with treatment-naive CHB, although it has several limitations.

This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy. Methods Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy. Results In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline. Conclusion Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.

Aim To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-M2BP) level and histological findings for patients with non-alcoholic steatohepatitis (NASH). Methods A total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFA+-M2BP level on severity of liver fibrosis comparing with other laboratory markers, including aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), FIB-4 index, platelet count and hyaluronic acid as serum liver fibrosis markers. Receiver–operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). Results The WFA+-M2B P-value ranged from 0.2 cut-off index (COI) to 9.6 COI (median, 0.9). The median values in each fibrosis stage were: 0.7 COI in F1, 0.7 COI in F2, 1.2 COI in F3 and 2.4 COI in F4 (P

AIM We aimed to examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) level and high-sensitivity C-reactive protein (hCRP) concentration and liver histological findings for patients with autoimmune hepatitis (AIH). METHODS A total of 84 AIH patients (median age, 64 years) were analyzed. We examined the effect of pretreatment WFA(+) -M2BP level and hCRP concentration on histological findings of liver fibrosis and liver inflammation activity comparing with other laboratory markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). RESULTS The median WFA(+) -M2BP values in each fibrosis stage were: 1.5 cut-off index (COI) in F1, 2.1 in F2, 3.3 in F3 and 9.8 in F4 (P

Aim We aimed to examine the relationship between serum Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-M2BP) levels and serum interferon-γ-inducible protein-10 (IP-10) levels and liver histological findings for patients with primary biliary cirrhosis (PBC) compared with other laboratory fibrotic or inflammatory parameters. Methods A total of 57 PBC patients were analyzed. Receiver–operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for WFA+-M2BP, IP-10 and four serum fibrosis markers for the presence of liver cirrhosis (F4) or advanced fibrosis (F3 or F4). Similarly, ROC analysis of WFA+-M2BP, IP-10, aspartate aminotransferase and alanine aminotransferase for the presence of severe inflammation activity (A3) was performed. Results There were eight men and 49 women (median age, 59 years). As for histological findings, F4 was observed in five patients, F3 in 11, F2 in 17, F1 in 24 and F0 in zero, whereas A3 was observed in seven patients, A2 in 27, A1 in 19 and A0 in four. The WFA+-M2BP levels ranged from 0.5 cut-off index (COI) to 13.6 COI (median, 1.8), while serum IP-10 levels ranged 121.9–1835.9 pg/mL (median, 571.5). For predicting liver cirrhosis, WFA+-M2BP yielded the highest AUROC (0.97, P

AIM There have been no established predictors of the outcome on sorafenib therapy for hepatocellular carcinoma (HCC) patients. We aimed to establish a new prognostic model suitable for sorafenib in HCC. METHODS Among 465 HCC patients treated with sorafenib in 14 hospitals, we formed a training cohort with 270 patients at seven hospitals located in West Japan and a validation cohort with 167 patients at seven hospitals located in East Japan. In the training cohort, we examined the relationship between overall survival (OS) and pretreatment clinical factors, and structured a new prognostic model. We verified this model in the validation cohort and compared with four existing staging models. RESULTS Multivariate analysis demonstrated distant metastases, portal invasion, intrahepatic tumor burden of more than 50%, serum α-fetoprotein of 150 ng/dL or more, des-γ-carboxyprothrombin of 1200 mAU/mL or more, albumin of 3.5 g/dL or less and total bilirubin of more than 1.0 mg/dL were significant independent adverse prognostic factors. We calculated a Japan Red Cross (JRC) score with these factors and classified three groups: low-, intermediate- or high-risk. Their median OS were well stratified (18.0, 8.8 and 3.7 months, respectively, P

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. In the last few decades, there has been a marked increase in therapeutic options for HCC and epidemiological characteristics at HCC diagnosis have also significantly changed. With these changes and advances in medical technology and surveillance program for detecting earlier stage HCC, survival in patients with HCC has significantly improved. Especially, patients with liver cirrhosis are at high risk of HCC development, and regular surveillance could enable early detection of HCC and curative therapy, with potentially improved clinical outcome. However, unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation, surgical resection or ablative therapies). Locoregional therapies such as radiofrequency ablation, percutaneous ethanol injection, microwave coagulation therapy and transcatheter arterial chemoembolization play a key role in the management of unresectable HCC. Currently, molecular-targeted agents such as sorafenib have emerged as a promising therapy for advanced HCC. The choice of the treatment modality depends on the size of the tumor, tumor location, anatomical considerations, number of tumors present and liver function. Furthermore, new promising therapies such as gene therapy and immunotherapy for HCC have emerged. Approaches to the HCC diagnosis and adequate management for patients with HCC are improving survival. Herein, we review changes of epidemiological characteristics, prognosis and therapies for HCC and refer to current knowledge for this malignancy based on our experience of approximately 4000 HCC cases over the last three decades.

Background & Aims There have been no established predictive factors of responders to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the factors predicting a good response to sorafenib in Japanese patients with HCC. Methods A total of 465 patients with unresectable HCC in the Japanese Red Cross Liver Study Group were treated with sorafenib between January 2008 and August 2013, and 316 patients with sufficient clinical data were analysed. To determine the factors predicting a good response, the relationships between radiological response and the following clinicopathological factors were analysed: age, gender, performance status, liver function, tumour status and decrease in serum alpha-foetoprotein (AFP) level after 1 month. Results This study included 259 males and 57 females with a median age of 70 years (range, 37–90 years), of which 191 (60.4%) were classified as Barcelona Clinic Liver Cancer stage C, and 271 (85.8%) had Child-Pugh class A liver function. The median overall survival time was 307 days and progression-free survival time was 109 days. According to the modified Response Evaluation Criteria In Solid Tumours, four patients achieved a complete response, 51 achieved a partial response, 136 had stable disease and 125 had progressive disease. Multivariate analysis identified female gender (P = 0.003) and decreased serum AFP level after 1 month (P = 0.042) as independent predictors of a complete or partial response. Conclusion Our results suggest female gender and a decrease in serum AFP level are independent predictors of good response to sorafenib.

Aim We aimed to determine whether pretreatment serum interferon-γ-inducible protein (IP)-10 concentration can predict response to telaprevir (TVR)-based triple therapy in patients with genotype 1 chronic hepatitis C (CHC), and to examine the effects of IP-10 concentration on liver histology. Methods Baseline IP-10 concentrations were measured in 97 patients with genotype 1 CHC treated with TVR-based triple therapy, and the associations between baseline IP-10 and treatment outcome were assessed by univariate and multivariate analyses. Associations between baseline serum IP-10 concentration and laboratory data and liver histological findings were also investigated. Results Median IP-10 concentration in these patients was 461.83 pg/mL (range, 151.35-4297.62). Multivariate analysis showed that IL28B genotype (P = 0.025) and IP-10 level (P = 0.004) were factors significantly predictive of rapid virological response (RVR), whereas in pretreatment factors only, IL28B genotype (P = 0.001) and liver fibrosis (P = 0.035) were independent predictors of sustained virological response. Using a cut-off IP-10 concentration of 460 pg/mL, patients with IL28B risk allele and low IP-10 had a significantly higher RVR rate than those with high IP-10 (P = 0.005). IP-10 concentration was significantly correlated with liver fibrosis (P = 0.001) and inflammation activity (P = 0.006) and had the highest areas under the curve for liver histological findings. Conclusion Baseline serum IP-10 level is a useful predictor of virological response in patients with genotype 1 CHC treated with TVR-based triple therapy, especially in patients with IL28B risk allele. IP-10 was well correlated with liver fibrosis and inflammation.

The liver is the major organ for the metabolism of protein, fat and carbohydrate. A nutritional approach is required in the treatment of cirrhosis, which is frequently complicated with protein-energy malnutrition. Several advanced treatment approaches for hepatocellular carcinoma (HCC) have been established in the past decade. HCC is often complicated by cirrhosis, so treatment of the underlying liver diseases is also necessary to improve the prognosis. Branched-chain amino acid (BCAA) granules were developed originally for the treatment of hypoalbuminemia associated with decompensated cirrhosis. However, subsequent studies found various other pharmacological actions of this agent. We review the clinical significance of therapy using BCAA granules in patients receiving different treatment approaches for cirrhosis and HCC based on the published work as well as our own data.

Aim To examine the effect of nucleoside analog (NA) therapy on clinical outcome in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent curative therapy. Methods A total of 131 patients with HBV-related HCC who underwent curative therapy were analyzed. They were divided into an NA group who received NA therapy (n = 99, group A) and a control group (n = 32, group B). Group A was further classified into two groups of patients who either received NA therapy before HCC therapy (n = 34, group Aa) or who received NA therapy with initial HCC therapy (n = 65, group Ab). Overall survival (OS) and recurrence-free survival (RFS) were compared in the three groups. Results The 1- and 3-year cumulative OS rates were both in group Aa, 100% and 88.0% in group Ab, and 100% and 75.7% in group B (overall significance, P = 0.002), respectively. The corresponding RFS rates were 93.1% and 36.0% in group Aa, 78.3% and 45.7% in group Ab, and 78.0% and 38.0% in group B (overall significance, P = 0.734), respectively. Multivariate analysis revealed that being part of group Aa (P

Aim To examine the effect of branched-chain amino acid (BCAA) therapy for patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib. Methods Seventy-eight subjects with unresectable HCC with a serum level of albumin of 3.5 g/dL or less treated with sorafenib were evaluated. They were classified into two groups: those receiving BCAA granules (n = 34; BCAA group) or a regular diet (n = 44; control group). We compared overall survival and administration period of sorafenib, and analyzed absolute changes in serum levels of albumin during sorafenib therapy in 41 patients who continued sorafenib therapy for 1 month or more with a follow up of more than 3 months. Results Median survival time (MST) in BCAA and control groups was 350 and 143 days (P = 0.007), respectively. Median administration period of sorafenib in the two groups was 59 and 41 days (P = 0.018). In the 41 patients described above, at 1 month, there was no significant change in the serum level of albumin between the two groups, but at 3 months, the difference in the absolute change in the serum level of albumin in the two groups reached significance (P = 0.023). In these subgroup analyses, the administration period of sorafenib as well as the MST in the BCAA group were significantly longer than those in the control group (P = 0.020 and = 0.004). Conclusion BCAA treatment during sorafenib therapy in HCC patients is useful for maintaining hepatic functional reserve, which may help to avoid early discontinuance of sorafenib therapy and improve survival.

Background The relationship between the thickness of subepithelial collagen bands (CB) and the development of linear ulcerations (LU) in collagenous colitis (CC) remains unclear. The aim of the present study was to compare the clinical and pathological features, including the thickness of CB, in CC patients with and without LU. Patients and Methods Twenty-five patients with CC diagnosed by pathological examination of biopsy specimens were analyzed. Eleven patients with LU (LU group) and 14 patients without LU (non-LU group) were compared. Results Ten patients in the LU group and seven in the non-LU group were taking lansoprazole (P = 0.038). Seven patients in the LU group and one in the non-LU group were taking non-steroidal anti-inflammatory drugs (NSAIDs) (P = 0.004). All LU were locatedin the transverse or left colon. Patients in the LU group were older than those in the non-LU group (P = 0.015). CB were significantly thicker in the LU group than in the non-LU group (mean ± SD, 40 ± 21 μm vs 20 ± 11 μm, P = 0.004). Multivariate analysis showed that NSAIDs use (odds ratio, 19.236; 95% confidence interval, 1.341–275.869) and CB thickness (odds ratio, 0.893; 95% confidence interval, 0.804–0.999) were independently associated with the development of LU. Conclusion Use of lansoprazole and NSAIDs, thick CB, and advanced age are associated with the development of LU in CC patients.