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•The hepatocellular carcinoma risk was not statistically different between the ETV and TDF groups.•The death or liver transplant risk was not statistically different between the 2 ...groups.•These results were consistently reproduced after adjusting for confounding variables.
It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB.
From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed.
In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years PY, respectively; adjusted hazard ratio HR 0.975 p = 0.852 by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 p = 0.884 and 0.998 p = 0.988, respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 p = 0.451). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 p = 0.385 and 1.239 p = 0.360, respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05).
The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results.
It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.
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.
To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.
From May 2005 to May 2007, cases of DILI ...(alanine transferase > 3 × upper normal limit or total bilirubin > 2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.
A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.
DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.
Hepatocellular carcinoma(HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of ...HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization( TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.
By using an extensive dataset of more than 32 million messages on 91 firms posted on the Yahoo! Finance message board over the period January 2005 to December 2010, we examine whether investor ...sentiment as expressed in posted messages has predictive power for stock returns, volatility, and trading volume. In intertemporal and cross-sectional regression analyses, we find no evidence that investor sentiment forecasts future stock returns either at the aggregate or at the individual firm level. Rather, we find evidence that investor sentiment is positively affected by prior stock price performance. We also find no significant evidence that investor sentiment from Internet postings has predictive power for volatility and trading volume. A distinctive feature of our study is the use of sentiment information explicitly revealed by retail investors as well as classified by a machine learning classification algorithm and a much longer sample period relative to prior studies.
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.
Summary
Background
Despite antiviral therapy, liver function often fails to recover in patients with hepatitis B virus (HBV)‐related decompensated cirrhosis.
Aim
To establish a prognostic model to ...predict re‐compensation in patients starting potent nucleos(t)ide analogue (NUC) therapy
Methods
We analysed 311 consecutive patients with HBV‐related decompensated cirrhosis treated with entecavir or tenofovir. The primary outcome was re‐compensation, defined as recovery to a Child–Pugh score of 5. The BC2AID score was developed from a cohort of 152 subjects based on competing risk models and validated in another cohort of 159 subjects.
Results
Re‐compensation occurred in 57.2% and 66.7% of the subjects in the derivation and validation cohorts, respectively. Six independent predictors for re‐compensation were identified in the derivation cohort and these comprised the BC2AID score: bilirubin ≤5 mg/dL (adjusted sub‐distribution hazard ratio aSHR 2.18), absence of severe complications (aSHR 2.78), alpha‐fetoprotein (AFP) ≥50 ng/mL (aSHR 2.54), alanine aminotransferase ≥200 IU/L (aSHR 2.62), international normalised ratio ≤1.5 (aSHR 2.37) and ≤6 months from initial decompensation until initiation of NUCs (aSHR 4.79). In the validation cohort, the area under the receiver operating characteristic curve of the BC2AID score for re‐compensation within 1 year of NUC therapy was significantly higher than that of the Child–Pugh, MELD, MELDNa and BE3A scores (0.813 vs 0.691, 0.638, 0.645 and 0.624, respectively; all P < 0.05).
Conclusions
Six clinical parameters, including AFP and the timing of antiviral therapy, were combined into a scoring system to accurately predict early re‐compensation in patients with HBV‐related decompensated cirrhosis.
The new model consisting of six factors was established to predict re‐compensation of patients with HBV‐related decompensated cirrhosis. It stratified the survival and re‐compensation well.
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.
Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested ...the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT.
Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR).
Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030).
HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.
Background/AimsMost prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum ...direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis. MethodsA total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level. ResultsMean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, "Direct Bilirubin, INR, and Creatinine" (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set. ConclusionsNew prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models.
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