According to the American Association for the Study of Liver Diseases (AASLD) treatment guidelines for hepatocellular carcinoma (HCC), the role of surgery has been expanded beyond the Barcelona ...Clinic Liver Cancer (BCLC) algorithm. We compared primary hepatectomy (PH) with transarterial chemoembolization (TACE) in patients with intermediate‐ to advanced‐stage (BCLC stage B/C) HCC to determine the current evidence. Through a database search, we included 18 high‐quality studies (one randomized controlled trial RCT, five propensity‐score matching nonrandomized comparative trials NRCTs, and 12 NRCTs) that compared survival outcomes of 5,986 patients after PH and TACE. We found significant survival benefits for PH over TACE in BCLC stage B/C patients (hazard ratio HR, 0.59; 95% confidence interval CI, 0.51‐0.67; P < 0.00001; I2 = 84%). According to the BCLC, both stage B and stage C patients showed significantly better overall survival (OS) for PH compared to TACE (HR, 0.53; 95% CI, 0.43‐0.65; P < 0.00001; I2 = 77%; HR, 0.67; 95% CI, 0.59‐0.77; P < 0.00001; I2 = 79%, respectively). Five‐year survival rates for PH were significantly higher than those for TACE in BCLC stage B/C, stage B, and BCLC stage C patients (odds ratio OR, 2.71, 2.77, and 3.03, respectively; all P < 0.00001). Survival benefits persisted across subgroup, sensitivity, and metaregression analyses; interstudy heterogeneity remained constant. Conclusion: This meta‐analysis suggests that surgical resection provides survival benefits in patients with intermediate‐ to advanced‐stage HCC. The evidence found herein may assist in the choice of treatment modality based on diverse definitions of operability. (Hepatology 2018).
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains ...unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
Nonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the ...diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676-0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724-0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.
The pathophysiology of functional bowel disorders is complex, involving disruptions in gut motility, visceral hypersensitivity, gut-brain-microbiota interactions, and psychosocial factors. Light ...pollution, as an environmental stressor, has been associated with disruptions in circadian rhythms and the aggravation of stress-related conditions. In this study, we investigated the effects of environmental stress, particularly continuous light exposure, on intestinal motility and inflammation using zebrafish larvae as a model system. We also evaluated the efficacy of probiotics, specifically
(
), at alleviating stress-induced constipation. Our results showed that continuous light exposure in zebrafish larvae increased the cortisol levels and reduced the intestinal motility, establishing a stress-induced-constipation model. We observed increased inflammatory markers and decreased intestinal neural activity in response to stress. Furthermore, the expressions of
and
, crucial for regulating water transport and intestinal motility, were altered in the light-induced constipation model. Administration of probiotics, specifically
, ameliorated the stress-induced constipation by reducing the cortisol levels, modulating the intestinal inflammation, and restoring the intestinal motility and neural activity. These findings highlight the potential of probiotics to modulate the gut-brain axis and alleviate stress-induced constipation. Therefore, this study provides a valuable understanding of the complex interplay among environmental stressors, gut function, and potential therapeutic strategies.
We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) ...over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa baseline, 13.9 ± 9.1 kPa 48 weeks, 11.7 ± 8.2 kPa 96 weeks, 10.09 ± 6.23 144 weeks, all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN.Clinical trials registration: ClinicalTrials.gov (NCT02865369).
To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF ...Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions.
We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea.
Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391).
The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.
AIM To investigate the factors affecting diagnostic delay and outcomes of diagnostic delay in inflammatory bowel disease（IBD） METHODS We retrospectively studied 165 patients with Crohn’s disease（CD） ...and 130 patients with ulcerative colitis（UC） who were diagnosed and had follow up durations > 6 mo at Korea University Ansan Hospital from January 2000 to December 2015. A diagnostic delay was defined as the time interval between the first symptom onset and IBD diagnosis in which the 76th to 100th percentiles of patients were diagnosed.RESULTS The median diagnostic time interval was 6.2 and 2.4 mo in the patients with CD and UC, respectively. Among the initial symptoms, perianal discomfort before diagnosis（OR = 10.2, 95%CI: 1.93-54.3, P = 0.006） was associated with diagnostic delays in patients with CD; however, no clinical factor was associated with diagnostic delays in patients with UC. Diagnostic delays, stricturing type, and penetrating type were associated with increased intestinal surgery risks in CD（OR = 2.54, 95%CI: 1.06-6.09; OR = 4.44, 95%CI: 1.67-11.8; OR = 3.79, 95%CI: 1.14-12.6, respectively）. In UC, a diagnostic delay was the only factor associated increased intestinal surgery risks（OR = 6.81, 95%CI: 1.12-41.4）.CONCLUSION A diagnostic delay was associated with poor outcomes, such as increased intestinal surgery risks in patients with CD and UC.
Summary
Background
Anti‐viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune‐tolerant phase.
Aims
To investigate the cumulative incidence of phase change and ...hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune‐tolerant phase.
Methods
In total, 946 patients in immune‐tolerant phase, defined as hepatitis B e antigen positivity, HBV‐DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes.
Results
The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV‐DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune‐tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV‐DNA level >107 IU/mL was associated independently with a reduced risk of phase change (hazard ratio HR = 0.734, P = 0.008), whereas a high ALT level, above the cut‐off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001).
Conclusions
The criterion of HBV‐DNA level > 107 IU/mL may be useful to define immune‐tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune‐tolerant phase.
Background/aims
Treatment responses of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remain unacceptably low and treatment modalities are limited. We compared the ...efficacy and safety of sorafenib and hepatic arterial infusion chemotherapy (HAIC).
Methods
In this randomized, prospective, comparative study, data on 58 patients with advanced HCC with PVTT, with Child–Turcotte–Pugh (CTP) scores of 5–7, were collected from six university hospitals between January 2013 and October 2015. Twenty-nine patients were treated with sorafenib and twenty-nine with HAIC.
Results
The median overall survival (OS) and time to progression (TTP) were significantly longer in the HAIC group than in the sorafenib group (14.9 vs.7.2 months,
p
= 0.012 and 4.4 vs. 2.7 months,
p
= 0.010). The objective response (OR) rates were 27.6 and 3.4% in the HAIC and sorafenib groups, respectively (
p
= 0.001). In univariate analysis, sex, main portal vein invasion and treatment modality were significant prognostic factors of OS (
p
= 0.044, 0.040, 0.015), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (
p
= 0.040, 0.002, 0.034, 0.014). In multivariate analysis, sex and treatment modality were significant prognostic factors of OS (
p
= 0.008, 0.005), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (
p
= 0.038, 0.038, 0.015, 0.011). Major complications included hyperbilirubinemia (44.8%), AST elevation (34.5%), ascites (13.8%) and catheter-related complications (3.4%) in the HAIC group and hyperbilirubinemia (34.5%), hand-foot syndrome (31.0%) and AST elevation (27.6%) in the sorafenib group.
Conclusions
For managing advanced HCC with PVTT, HAIC may be a valuable treatment modality.
Several studies have recently suggested that liver disease and cirrhosis were risk factors for poor outcomes in patients with coronavirus disease 2019 (COVID-19) infections. However, no large data ...study has reported the clinical course of COVID-19 patients with chronic hepatitis B virus (HBV) infections. This study investigated whether HBV infection had negative impacts on the clinical outcomes of COVID-19 patients.
We performed a nationwide population-based cohort study with 19,160 COVID-19-infected patients in 2020 from the Korean Health Insurance Review and Assessment database. The clinical outcomes of COVID-19 patients with chronic HBV infections were assessed and compared to those of non-HBV-infected patients.
Of the 19,160 patients diagnosed with COVID-19, 675 (3.5%) patients had chronic HBV infections. The HBV-infected patients were older and had more commodities than the non-HBV infected COVID-19 patients. During the observation period, COVID-19-related mortality was seen in 1,524 (8.2%) of the non-HBV-infected 18,485 patients, whereas 91 (13.5%) in HBV-infected 675 patients died of COVID-19 infection. Compared to patients without HBV infections, a higher proportion of patients with chronic HBV infections required intensive care unit (ICU) admission and had organ failures. However, odds ratios for mortality, ICU admission, and organ failure were comparable between the two groups after adjusting for age, sex, and comorbid diseases including liver cirrhosis and hepatocellular carcinoma.
COVID-19-infected patients with HBV infections showed worse clinical courses than non-HBV-infected COVID-19 patients. However, after adjustment, chronic HBV infection itself does not seem to affect the clinical outcomes in COVID-19 patients.
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