Impact of Low Muscle Mass on Hepatocellular Carcinoma Patients Undergoing Transcatheter Liver-Directed Therapies: Systematic Review & Meta-Analysis.

BACKGROUND AND AIM: Transcatheter liver-directed intra-arterial therapies are mainstream treatment options for intermediate-stage hepatocellular carcinoma (HCC). However, the effect of low skeletal muscle mass (LSMM) on overall survival (OS) in these patients remains uncertain. We aimed to ascertain the prevalence and prognostic effect of LSMM in this population. METHOD: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed in the PubMed and Embase databases until Oct 2023. Random-effects meta-analysis was performed to determine the pooled prevalence of LSMM and calculate the hazard ratio (HR) for OS with a 95% confidence interval (CI) in patients with intermediate-stage HCC undergoing various transarterial therapies, comparing those with and without LSMM. RESULTS: Twelve studies involving 2450 patients were included. The pooled prevalence of LSMM was 46% (95% CI, 38-55%), and the results were consistent across different treatments, regions, and age subgroups. The meta-analysis indicated that LSMM was significantly associated with decreased OS (HR, 1.78; 95% CI, 1.36-2.33; I2, 75%). Subgroup analyses reassured the main findings across various therapies, including transarterial chemoembolization (TACE) (HR, 1.68; 95% CI, 1.23-2.30; I2, 81%), transarterial embolization (TAE) (HR, 2.45; 95% CI, 1.42-4.22; I2, 0%), and transarterial radioembolization (TARE) (HR, 1.94; 95% CI, 1.01-3.73; I2, 0%). CONCLUSIONS: In intermediate-stage HCC, LSMM is common and associated with reduced OS. To achieve an optimal prognosis, clinicians should incorporate routine LSMM measurement into practice, while caring for patients with intermediate-stage HCC, irrespective of TACE, TAE, and TARE.

Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis.

Low skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n = 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0-50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46-1.97) and PFS (HR, 1.32; 95% CI, 1.16-1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.

Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Transarterial chemoembolization with or without sorafenib for hepatocellular carcinoma: A real-world propensity score-matched study.

Objectives: Transarterial chemoembolization (TACE) or sorafenib may prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, whether their combination prolongs survival than TACE alone remains controversial. We aimed to compare the overall survival (OS) of patients with unresectable HCC treated with TACE plus sorafenib (TACE-S) versus TACE alone. Materials and Methods: All patients with unresectable HCC who received TACE as the initial therapy between January 2006 and January 2017 at Taipei Tzu Chi Hospital were enrolled. We matched patients treated with TACE-S and those treated with TACE alone (TACE) by performing propensity score matching at a 1:2 ratio. Our primary outcome was OS during a 10-year follow-up period, and represented as a hazard ratio calculated using Cox proportional hazard regression models. Results: Among 515 patients with unresectable HCC were treated initially with TACE, 56 receiving TACE-S group and 112 receiving TACE alone (TACE group) were included in the primary outcome analysis. The TACE-S group had significantly longer median OS than did the TACE group (1.55 vs. 0.32, years; P < 0.001), and the 5-year OS rates was 10.7% in the TACE-S group and 0.9% in the TACE group (P < 0.001). In multivariate analyses, patients with a lower Child-Pugh score, tumor size ≤5 cm, and no extrahepatic metastasis before treatment and those receiving antiviral agents and receiving TACE-S had longer OS (all P < 0.001). Conclusion: Antiviral agents and the combination of TACE with sorafenib may improve the OS of patients with unresectable HCC.

Management of non-alcoholic fatty liver disease in patients with sarcopenia.

INTRODUCTION: Sarcopenia usually occurs with aging, sedentary lifestyle, unhealthy dietary habits, and chronic disorders pathophysiologically and bi-directionally linked to obesity and nonalcoholic fatty liver disease (NAFLD). Because of the global increase in aging and obesity populations, patients with concomitant sarcopenia and NAFLD are common, accompanied by various disorders relevant to obesity and sarcopenia, with across-the-board impact on socio-economic and public health life worldwide. Therefore, developing effective and practical management of these patients has become a pressing clinical issue. AREAS COVERED: The authors searched literature from PubMed and Ovid MEDLINE up until Feb 2020. Emerging data on the management of sarcopenia and nonalcoholic fatty liver disease were examined and discussed. EXPERT OPINION: Although NAFLD in patients with sarcopenia has become a critical problem worldwide, we still don't know much about the management of such patients. Based on theoretical speculations, we can recommend lifestyle intervention, including diet control with adequate protein intake, exercise intervention, and weight reduction as the mainstay of management at the first stage. More studies are needed in the future to identify the most suitable treatment and solve this important problem.

Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS: From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS: The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION: The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).

Ropeginterferon alfa-2b every 2 weeks as a novel pegylated interferon for patients with chronic hepatitis B.

BACKGROUND: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8-14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. METHODS: Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 µg (group 1), q2w 450 µg (group 2) or q1w PEG-IFN alfa-2a 180 µg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). RESULTS: The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 µg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). CONCLUSION: In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B.

Use of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus infection and severe renal impairment.

BACKGROUND/AIMS: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. METHODS: We prospectively recruited patients with Child's A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017-2018 to receive GLE/PIB treatment. RESULTS: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. CONCLUSION: GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Hepatitis C virus genotypes 1-3 infections regulate lipogenic signaling and suppress cholesterol biosynthesis in hepatocytes.

BACKGROUND: Patients with different hepatitis C virus (HCV) genotype infections are associated with varying metabolic disorders. Although alteration of lipid metabolism has been confirmed as a virus-induced metabolic derangement in chronic hepatitis C patients, the impact of various HCV genotypes on hepatic cholesterol metabolism remains elusive. In this study, we thus investigated the HCV genotype-specific lipogenic and cholesterol metabolism profiles in an in vitro cell culture system. METHODS: We first conducted HCV cell culture system (HCVcc) assays by infecting Huh7.5.1 cells with multiple infection-competent HCV strains, including the genotype 2a JFH1 and JFH1-based intergenotypic recombinants 1b and 3a. We then examined the expression levels of various lipid and cholesterol-related genes. RESULTS: The data showed that infection with individual HCV genotypes exerted unique gene expression regulatory effects on lipoproteins and cholesterol metabolism genes. Of note, all HCV strains suppressed cholesterol biosynthesis in hepatocytes through downregulating the expression of HMG-CoA reductase (HMGCR) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - two essential enzymes for cholesterol biosynthesis. These HCV-mediated inhibitory effects could be reversed by treatment with sofosbuvir, a pangenotypic NS5B inhibitor. In addition, overexpression of HCV genotype 1b, 2a or 3a core protein significantly suppressed HMGCR mRNA transcription and translation, thus diminished cellular cholesterol biosynthesis. Nonetheless, the core protein had no effect on FDFT1 expression. CONCLUSION: Although HCV infection regulates host lipid metabolism in a genotype-specific manner, its inhibition on hepatocellular cholesterogenic gene expression and total cholesterol biosynthesis is a common effect among HCV genotype 1b, 2a and 3a.

Similarities and differences between IBS-C and FC with regards to symptomatology, sleep quality and psychological attributes.

BACKGROUND: Irritable bowel syndrome (IBS) and functional constipation (FC) are highly prevalent in the general population and have significant symptom overlap, while the clinical associations and psychological links between IBS and FC remains poorly understood. We aimed to compare the clinical, metabolic and psychological factors between patients with FC patients and constipation predominated IBS. METHODS: We consecutively enrolled 360 patients from the outpatient clinics of Hualien Tzu Chi medical center. Constipation-predominant IBS (IBS-C) and FC were diagnosed based on Rome III criteria. All participants completed the Pittsburg Sleep Quality Index (PSQI) score, the State Trait Anxiety Inventory (STAI) score and the Taiwanese Depression Questionnaire (TDQ) score. RESULTS: Fifty-four patients had FC and twenty-three patients had IBS-C. Compared to asymptomatic controls, FC/IBS-C groups had female predominance (p < 0.001), FC as well as more GI discomforts and inferior psychosocial characteristics (p < 0.05). Compared to FC, IBS-C had higher severity scores of abdominal distention (4.52 ± 1.90 vs. 3.07 ± 1.88) and heartburn (2.17 ± 1.50 vs. 1.46 ± 1.14). However, FC was independently associated with poor sleep quality [adjusted OR: 1.19 (1.08-1.31), p < 0.001] and IBS-C with depression [adjusted OR: 1.07 (1.02-1.12), p = 0.005]. CONCLUSION: Patients with FC and IBS-C shared many similar GI complaints and psychosocial characteristics, however IBS-C had more severe bloating, heartburn and depression and FC had worse sleeping quality.

Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms. METHODS: This study enrolled 303 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non-dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances. RESULTS: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms. CONCLUSIONS: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms.

Impact of concomitant dyspepsia and irritable bowel syndrome on symptom burden in patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.

Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity.

BACKGROUND/AIMS: We aimed to investigate gastrointestinal symptoms, clinical characteristics, and psychological factors in subjects with and without sleep disturbance (SD) in a health screening cohort. METHODS: We enrolled 2,752 consecutive subjects during their health checkups. All participants underwent an evaluation with questionnaires. Demographic characteristics and biochemical data were recorded. SD was confirmed when Pittsburgh Sleep Quality Index score was greater than 5. RESULTS: Among the study population (n = 2,674), 956 (36%) individuals had SD. SD was associated with female gender, older age, lower level of education, higher systolic blood pressure, higher serum high-density lipoprotein levels and higher prevalence of functional dyspepsia and irritable bowel syndrome (IBS). SD subjects also had more depression, more anxiety, more severe gastrointestinal reflux disease symptoms and higher prevalence of non-erosive reflux disease (NERD; p < 0.001). SD was -independently associated with female gender (OR 1.75, p < 0.001), older age (OR 1.03, p < 0.001), NERD (OR 1.88, p = 0.004), IBS (OR 1.51, p = 0.043), and depression (OR 1.16, p < 0.001) by multivariate analysis. CONCLUSIONS: Future studies will be needed to clarify the interrelationships among SD, psychological stress, and functional gastrointestinal disorders.

Association of coffee consumption and liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B: A 5-year population-based cohort study.

BACKGROUND/PURPOSE: Although coffee consumption has been associated with decreased risk of liver fibrosis progression, cirrhosis or hepatocellular carcinoma in patients with HCV infection or fatty liver diseases, its effect on hepatitis B patients remains unclear. We aimed to examine the effect of coffee consumption on liver fibrosis progression and cirrhosis-related complications in patients with chronic HBV infection. METHODS: Coffee consumption was assessed in 2604 participants who were previously recruited from a population-based GERD survey. The primary endpoints of this study were the impact of coffee consumption on the development of cirrhosis-related complications, including liver cirrhosis, esophageal varices, or hepatocellular carcinoma at the end of 5-year follow-up. The secondary endpoints were the declines of serum predicting indices of liver fibrosis (AST/ALT, APRI, FIB-4, Hui score) or liver function tests (AST, ALT). RESULTS: 328 patients with chronic HBV infection were enrolled into this study. At baseline, coffee consumption was associated with higher education level, more frequent tobacco use and normal blood pressure (p < 0.05 for all). Patients with higher coffee consumption had a significant lower serum AST, APRI and FIB-4 index value than non-coffee drinkers [adjusted HR 0.30, 95% CI(0.11-0.82) for AST; 0.30, 95% CI (0.11-0.84) for APRI; 0.30, 95% CI (0.13-0.69) for FIB-4]. However, higher coffee consumption didn't change serum AST levels, APRI, FIB-4 index values or incidences of cirrhosis-related complications at the end of 5-year follow-up. CONCLUSION: Coffee consumption was not associated with fibrosis progression or HCC risk in chronic hepatitis B patients over the 5-year observation period.

Risks of hepatocellular carcinoma and cirrhosis-associated complications in patients with rheumatoid arthritis: a 10-year population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: Although rheumatoid arthritis (RA) has been linked to several important malignancies, data for the risks of hepatocellular carcinoma (HCC) in patients with RA are scarce. We aimed to examine the risk of HCC and cirrhosis-associated complications and the use of biologics in a national representative RA sample in Taiwan. METHODS: All study subjects aged ≥ 18 years in the Taiwan National Health Insurance program between January 1, 2000, and December 31, 2009 were enrolled. We matched RA and non-RA subjects by propensity scores in a 1:1 ratio. Our primary outcome was a diagnosis of HCC and cirrhosis-associated complications during a 10-year follow-up period. The risk of outcomes was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models. RESULTS: 24,245 RA and 24,245 non-RA subjects were included in the primary outcome analysis. Mean overall person-years (PY) of follow-up were 116,608 PY for the RA cohort, and 234,280 PY for the non-RA cohort. The overall incidence of HCC and cirrhosis-associated complications was lower in the RA cohort than in the non-RA cohort (0.66% vs. 1.41% HCC events and 1.45% vs. 1.95% cirrhosis-associated complications events during 10-year follow-up). The HRs adjusted for age, sex, the frequency of medical visits, and CCI were 0.57 (0.46-0.71) for HCC and 0.67 (0.59-0.76) for HCC and cirrhosis-associated complications. Although immunomodulatory agents may alter the risk of malignancy, use of biologics did not increase HCC risk in RA patients. CONCLUSIONS: RA is associated with a reduced risk of developing HCC and cirrhosis-associated complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02880306.

Sarcopenia and chronic liver diseases.

INTRODUCTION: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with various chronic diseases, including chronic liver diseases. Growing lines of evidence indicate that sarcopenia not only correlates with the clinical outcomes and survival of patients undergoing liver transplant, but also serves as a prognostic factor for candidates of liver transplantation and patients with hepatocellular carcinoma. Areas covered: In this review, we conducted a narrative review and search of literature from PubMed, Ovid MEDLINE, and the Cochrane Library database up to August 2018. Studies relevant to the emerging data of sarcopenia and chronic liver diseases were examined and discussed. Expert commentary: Although sarcopenia has been shown to play a vital role in the outcomes of cirrhotic patients with or without liver transplant, its impact on non-cirrhotic patients remains unclear and deserves future research efforts. To develop an effective and practical measurement of sarcopenia has become an urgent issue in the management of patients with chronic liver diseases. ABBREVIATIONS: HCC: hepatocellular carcinoma; L3SMI: third lumbar vertebra skeletal muscle index; NAFLD: nonalcoholic fatty liver disease; VAT: visceral adipose tissue; PMA: psoas muscle area; LT: liver transplantation; AUC: area under the curve; LC: liver cirrhosis; SPPB: short physical performance battery; HU: Hounsfield units; ASM: appendicular skeletal muscle; SMI: skeletal muscle index; FLI: fatty liver index; PCLD: polycystic liver disease; DEXA: dual energy X-ray absorptiometry; BCAAs: branched-chain amino acids; BIA: bioelectrical impedance analysis; CT: computed tomography; OS: overall survival; CSA: cross-sectional area; NASH: nonalcoholic steatohepatitis; TPMT: transversal psoas muscle thickness; IMAC: intramuscular adipose tissue content; LDLT: living donor liver transplantation; PMI: psoas muscle mass index; PMTH: psoas muscle thickness by height; TPA: total psoas area; OLT: orthotopic liver transplantation; 6MWD: Six-minute walk distance; HRQOL: health-related quality of life; SMA: skeletal muscle area.

An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

Overlap of Dyspepsia in Patients with Gastroesophageal Reflux Disease: Impact of Clinical, Metabolic, and Psychosocial Characteristics.

BACKGROUND: Gastroesophageal reflux disease (GERD) and dyspepsia are highly prevalent in the general population with significant symptom overlap, while the interaction between both remains poorly understood. AIM: To examine whether GERD overlapping dyspepsia would have an impact on clinical and psychological features as compared with GERD alone. METHODS: We performed a cross-sectional study in a GERD cohort (n = 868) that was previously recruited from a population-based GERD survey (n = 2752). We compared the clinical and psychological factors between patients with and without dyspeptic symptoms "epigastric pain or burning." All participants were evaluated with Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. Endoscopic findings were classified according to the Los Angeles classification. RESULTS: Among the GERD population, 107 subjects had overlapping "epigastric pain or burning" (GERD-D), and 761 did not have these symptoms (GERD alone). GERD-D subjects had more severe GERD symptoms and were more often associated with irritable bowel syndrome (IBS) (OR 3.54, 95% CI 1.92-6.52) as compared subjects with GERD alone. In addition, GERD-D subjects had lower quality of sleep (OR 1.11, 95% CI 1.01-1.21), higher depression (OR 1.06, 95% CI 1.02-1.10), lower blood pressure (OR 0.45, 95% CI 0.22-0.95), and higher serum total cholesterol levels (OR 2.78, 95% CI 1.36-5.67) than GERD alone. CONCLUSIONS: GERD-D subjects are characterized with worsening clinical symptoms as well as higher psychosocial, IBS, and metabolic comorbidities, but less erosive esophagitis. Our results indicate that clinical awareness of such overlapping condition would help optimize the management of GERD in clinical practice.