Effect of a 12-week home-based exercise training program on aerobic capacity, muscle mass, liver and spleen stiffness, and quality of life in cirrhotic patients: a randomized controlled clinical trial.

BACKGROUND: Physical inactivity and sarcopenia are two important predictors associated with increased morbidity and mortality in patients with cirrhosis. At present, the benefit of a home-based exercise training program is not well established in cirrhotic patients. The main objective of this study was to evaluate the effect of a 12-week home-based exercise training program on aerobic capacity in cirrhotic patients. METHODS: This is a randomized controlled study. Patients with compensated cirrhosis were randomized by a block of 4 with concealed allocation to the home-based exercise training (n = 20) or control (n = 20). Both groups received protein supplementation (9 g/day) for 12 weeks. The home-based exercise training program included several aerobic/isotonic moderate-intensity continuous training exercises for 40 min per session, at least four times a week, with a total duration of 12 weeks. The heart rate was continuously monitored using a Garmin® watch. In the control group, patients received exercise instruction without active encouragement and continuous monitoring. The primary outcome was a change in the 6-min walk test from baseline. Secondary outcomes were the difference in thigh muscle thickness, liver stiffness, spleen stiffness, and quality of life. RESULTS: A total of 40 patients were enrolled prospectively. The mean age was 56.3 ± 7.8 years, with a male predominance of 65%. The mean body mass index was 25.23 ± 3.0 kg/m2, and all were Child-Pugh A. Chronic hepatitis B or C was the primary cause of cirrhosis. The baseline values were a 6-min walk test of 475 ± 70 m, liver stiffness of 15.3 ± 9.3 kPa, spleen stiffness of 29.8 ± 21.7 kPa, and thigh muscle thickness (average compression index) of 0.64 ± 0.2 cm/m2. All baseline characteristics between the two groups were not different except the mean muscle mass which was significantly higher in the home-based exercise training group (p = 0.03, 95% CI 0.01 to 0.17). At the end of the study, no significant difference in the 6-min walk test was observed (p = 0.36, 95% CI -15.5 to 41.7). Liver stiffness measurement significantly improved in both groups, but no significant difference between groups was demonstrated (p = 0.77, 95% CI -1.3 to 1.8). Thigh muscle thickness was not different between groups. The fatigue domain of the quality of life index was significantly improved in the home-based exercise training group compared with the control group (p = 0.05, 95% CI 0.00 to 0.67). No adverse events occurred in a home-based exercise training program. CONCLUSIONS: A 12-week moderate-intensity home-based exercise training program in compensated cirrhotic patients significantly improved the fatigue domain of the quality of life index without an increase in adverse events. However, no benefit in terms of aerobic capacity, thigh muscle mass, liver stiffness, and spleen stiffness was demonstrated. TRIAL REGISTRATION: Thai Clinical Trials Registry number TCTR20190926002, 26/09/2019 (Retrospectively registered).

Impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with coexisting hepatitis B virus infection.

Continuously updated information is helpful for evaluating the safety of long-term systemic drug use in psoriasis patients with concomitant hepatitis B virus (HBV) infection. To investigate the impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with HBV infection. Data of patients during 10-year period were recorded and analyzed. Sixty-six patients (46 males and 20 females) with a mean age of 58.5 ± 13.1 years were recruited. Our study estimated that the 5-year cumulative risks of developing cirrhosis and HCC were 30% and 5%, respectively, in patients receiving systemic treatments for psoriasis. Risks of cirrhosis and HCC were not significantly different between systemic and topical treatment groups. Thirty patients were prescribed systemic treatments (acitretin, methotrexate, ciclosporin, and anti-tumor necrosis factors). Three HBsAg+ patients developed viral reactivation (two patients with methotrexate and one patient with ciclosporin). The effects of systemic treatments for psoriasis on liver outcome in patients with coexisting HBV infection are needed to be determined. HBsAg+ patients are more likely to develop viral reactivation during systemic treatment for psoriasis than HBsAg- patients. Monitoring of liver enzymes and HBV DNA every 3 months is recommended during treatment and for 6 to 12 months after drug discontinuation.

Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B.

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients. Methods: Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events. Results: In accordance with Brunt's classification, 408 patients had steatohepatitis (n=34), "steatosis but not steatohepatitis" (n=118), or "non-steatosis" (n=256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events. Conclusions: Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.

A Novel and Simplified Score for Determining Treatment Eligibility for Patients with Chronic Hepatitis B.

Background: International guidelines for hepatitis B infection (HBV) recommend initiating antiviral treatment based on viral replication with inflammation or fibrosis. HBV viral loads and liver fibrosis measurements are not widely available in resource-limited countries. Aim: To develop a novel scoring system for the initiation of antiviral treatment in HBV-infected patients. Methods: We examined 602 and 420 treatment-naïve, HBV mono-infected patients for derivation and validation cohorts. We performed regression analysis to identify parameters associated with the initiation of antiviral treatment based on the European Association for the Study of the Liver (EASL) guidelines. The novel score was developed based on these parameters. Results: The novel score (HePAA) was based on HBeAg (hepatitis B e-antigen), the platelet count, alanine transaminase, and albumin. The HePAA score showed excellent performance, with AUROC values of 0.926 (95% CI, 0.901-0.950) for the derivation cohort and 0.872 (95% CI, 0.833-0.910) for the validation cohort. The optimal cutoff was ≥3 points (sensitivity, 84.9%; specificity, 92.6%). The HePAA score performed better than the World Health Organization (WHO) criteria and the Risk Estimation for HCC in Chronic Hepatitis B (REACH-B) score, and it performed similarly to the Treatment Eligibility in Africa for HBV (TREAT-B) score. Conclusions: The HePAA scoring system is simple and accurate for chronic hepatitis B treatment eligibility in resource-limited countries.

Genetic polymorphism of low-density lipoprotein receptor did not affect treatment outcome of chronic hepatitis C genotype 3.

BACKGROUND: The low-density lipoprotein receptor (LDL-R) has been proposed to function as a receptor for the hepatitis C virus (HCV) entry. Polymorphism of LDL-R gene may influence the clearance of virus and response to treatment. This study was conducted to evaluate the association of LDL-R gene polymorphism and the response to antiviral treatment in patients with chronic HCV infection. MATERIAL AND METHOD: A total of 112 naïve patients with HCV genotype 3 were enrolled in the study. All patients were treated with a combination of pegylated interferon and ribavirin for 24 weeks. Polymerase chain reaction combined with restriction fragment length polymorphism was used to detect the polymorphism at the LDL-R gene intron 11 loci, including intron1, intron 3.1, intron 3.2, intron 4, intron 6, exon 8, intron 11, intron 13, intron 14 and 3'UTR-2 SNPs in intron 16 region. Comparisons of genotype and allele frequency between responders and nonresponders were analyzed. RESULTS: Patients had a mean age of 54 years and 43% were male. Mean HCVRNA viral load and alanine aminotransferase level were 6.3 log, IU/mL and 100 IU/L, respectively. Sustained virological response, relapse and no response were documented in 68.7%, 17.9% and 13.4%, respectively. Baseline characteristics including age, sex, body weight, aminotransferase levels and HCV RNA viral load were similar between responders and nonresponders. No statistical difference was found for either genotype distribution or allele frequency among responders and nonresponders. CONCLUSION: This study did not provide the evidence for a role of LDL-R polymorphism the response to antiviral treatment in patients with HCV genotype 3. This indicates that a genetic component via the LDL-R may not control HCV treatment outcome in HCV genotype 3

How do we treat psoriasis patients with hepatitis C infections in real-world situations? A retrospective analysis of 34 patients.

BACKGROUND: There is still relatively limited data on psoriasis and hepatitis C virus (HCV) infections. OBJECTIVE: This study investigated the clinical characteristics and treatment of psoriasis patients with HCV infections in real-world practice. METHODS: Medical records of all psoriasis patients with HCV infections who attended the outpatient clinic at Siriraj Hospital over a 10-year period were retrospectively reviewed. RESULTS: Of 34 patients, 26 and 8 patients were men and women, respectively with a mean age of 57.0 ± 8.7 (range, 42.2-77.2) years. The median age of psoriasis onset was 42.7 ± 12.7 (range, 8-67.25) years. With a median follow-up period of 13.6 years, cirrhosis and hepatocellular carcinoma were found in 67.6% and 29.4% of the patients, respectively. The interferon used for HCV treatment exacerbated the psoriasis in 20% of those patients. Conventional treatments and anti-tumor necrosis factors (anti-TNFs) were used in strict collaboration with hepatologists. No patients experienced a worsening of their HCV infection. CONCLUSION: Despite a limited number of patients, a male predominance and late-onset psoriasis were frequently observed. Although, interferon therapy for HCV can exacerbate psoriasis, it is not contraindicated. All conventional treatments and anti-TNFs can be used, provided that there is strict collaboration with hepatologists.

Validation of the prognostic models in acute-on-chronic liver failure precipitated by hepatic and extrahepatic insults.

BACKGROUND: Patients with acute-on-chronic liver failure (ACLF) precipitated by hepatic injury and extrahepatic insults had distinct clinical phenotypes, and prognosis. This study aimed to validate prognostic models for ACLF and to explore their discriminative abilities in ACLF population categorized by the etiologies of precipitating events. METHODS: This study collected data from 343 consecutive cirrhotic patients hospitalized with the diagnosis of ACLF according to the EASL-CLIF-Consortium definition. The discrimination abilities of prognostic models at the onset of ACLF were tested with the concordance index and area under the receiver operating characteristic curve. RESULTS: Among the entire cohort, 103 patients survived with medical management, nine patients were transplanted, and 231 patients died without liver transplantation. The predictive accuracy of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) for 28-day mortality was similar to the CLIF Consortium Organ Failure (CLIF-C OF) but significantly higher than the CLIF Consortium ACLF, the Child-Turcotte-Pugh, the model for end-stage liver disease (MELD), the MELD-sodium, the integrated MELD, and the Acute Physiology and Chronic Health Evaluation II. Of note, 44 patients had acute hepatic insult triggering ACLF (hepatic-ACLF), 244 were exclusively precipitated by bacterial infection or gastrointestinal bleeding (extrahepatic-ACLF), and 55 cases had no any identifiable potential precipitating events. Patients with hepatic-ACLF had significantly higher 28-day mortality than extrahepatic-ACLF patients. The CLIF-SOFA and CLIF-C OF displayed the highest accuracy significantly outperforming other scoring systems in predicting mortality among patients with hepatic-ACLF and those with extrahepatic-ACLF. CONCLUSION: The CLIF-SOFA and simpler CLIF-C OF are reliable measures of mortality risk in ACLF patients precipitated by either hepatic or extrahepatic insults. Both validated models could be used to stratify the risk of death and improve management of ACLF.

Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice.

INTRODUCTION: Better treatment outcome of early-stage hepatocellular carcinoma (HCC) warrants employment of screening programs, in which ultrasonography (US) and serum alfa-fetoprotein (AFP) have been recommended. Considering cost-effectiveness, serum AFP has recently been withdrawn from several guidelines for HCC surveillance. However, there were limited studies on benefits of AFP for HCC surveillance in Thailand. MATERIALS AND METHODS: This is a retrospective study of a proportion of HCC cases in which a diagnostic study was triggered by high serum AFP levels, but US failed to detect the lesion. Patients who received diagnostic imaging for HCC at Siriraj Hospital between January 1, 2012 and December 31, 2014 were included. All the patients must fulfill criteria for HCC surveillance according to American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of HCC 2010 or European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer (EASL-EORTC) Clinical Practice Guidelines: Management of HCC 2012. Previous diagnosis of any liver malignancy was excluded. Demographic data, underlying liver diseases, screening of AFP and US results, and definite diagnosis of HCC were recorded. RESULTS: Of the 452 cases who fulfilled inclusion and exclusion criteria, chronic hepatitis B, C, and alcoholic cirrhosis were accountable for 53.8, 25.9, and 7.3% respectively. Totally, 150 cases were diagnosed with HCC. Additional HCC detection rate by high serum AFP but failed US of 15.3% was demonstrated. Subgroup analysis revealed significant benefit of AFP in cirrhotic patients with chronic hepatitis B and C (p-value 0.004 and 0.002). No significant benefit was observed in cirrhosis of other causes and in noncirrhotic chronic hepatitis B. CONCLUSION: We reported a 15.3% additional benefit of serum AFP for HCC surveillance in conjunction with US of liver. Chronic hepatitis B and C with cirrhosis significantly derived the benefit from serum AFP screening.How to cite this article: Lersritwimanmaen P, Nimanong S. Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice. Euroasian J Hepato-Gastroenterol 2018;8(1):83-87.

CD40 Signaling Drives Potent Cellular Immune Responses in Heterologous Cancer Vaccinations.

Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting either MHC class I or II neoantigens or tumor-associated antigens rendered up to 60% of the total T-cell population specific for a single tumor epitope. DC/CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximum flexibility regarding the choice of antigen. Cancer Res; 77(8); 1918-26. ©2017 AACR.