Background and Aim
The prevalence of metabolic dysfunction‐associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease ...severity is elusive.
Methods
A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non‐MAFLD subjects with advanced liver disease.
Results
Two thousand two hundred and forty‐two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti‐HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non‐viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P < 0.001). Factors associated with advanced fibrosis included age (odds ratio OR/95% confidence interval CI: 4.8/3.7–6.0, P < 0.001), male sex (OR/CI: 1.3/1.0–1.7, P = 0.019), anti‐HCV seropositivity (OR/CI: 5.9/4.6–7.5, P = 0.019), MAFLD‐lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3–5.2, P = 0.005; compared with the non‐MAFLD group) and MAFLD‐diabetes (OR/CI: 1.5/1.1–2.1, P = 0.008; compared with the non‐MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD‐lean MS group (OR/CI: 9.1/2.4–34.6, P = 0.001; compared with non‐MAFLD group) and MAFLD‐DM group (OR/CI: 2.0/1.2–3.2, P = 0.004; compared with non‐MAFLD group).
Conclusions
MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non‐viral hepatitis subjects in a community level.
The advantage of colchicine to promote sorafenib or regorafenib anti-cancer effects on hepatocellular carcinoma (HCC) was investigated. Four primary cultured HCC cell lines (S103, S143, S160, S176) ...were studied by clinically achievable plasma sorafenib (5, 10 μg/mL), regorafenib (2, 4 μg/mL) and colchicine (4 ng/mL) concentrations. Sorafenib and regorafenib target genes and cancer stem cell markers (NANOG, POU5F1) were selected for experiments. Colchicine inhibited proliferation in all cell lines. Sorafenib inhibited proliferation only in S143 (5 μg/mL). Combined colchicine with sorafenib reversed the sorafenib effect on cellular proliferation from promotive to inhibitory in S103, and demonstrated anti-proliferative effects on other cell lines. Regorafenib inhibited proliferation in S103 (2 μg/mL), S176 (2 μg/mL) and S160 (4 μg/mL). Combined colchicine with regorafenib demonstrated equal or stronger anti-proliferative effects than regorafenib alone in all cell lines except S160. Combined colchicine obliterated or reduced the number of up-regulated target genes induced by sorafenib, and demonstrated equal or increased number of down-regulated target genes as compared with regorafenib alone. However, combined colchicine with regorafenib increased one up-regulated target gene in three cell lines. Colchicine obliterated or decreased the magnitude of up-regulated NANOG induced by sorafenib (S103, S143, S176) or regorafenib (S143), and combined with regorafenib could down-regulate NANOG (S160, S176). Adding colchicine to sorafenib or regorafenib showed inconsistent influence on POU5F1 expression as compared with sorafenib or regorafenib alone. The above results suggest that the anti-cancer effects of combined sorafenib with colchicine may be better than sorafenib alone. Colchicine may be added to regorafenib non-responders.
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•Hepatocellular carcinoma is composed by cancer cells with various characters.•Multikinase inhibitor resistant cells will replace sensitive cells after treatment.•Colchicine can inhibit proliferation in cancer cells with different characters.•Combined sorafenib with colchicine may be better than sorafenib alone.•Colchicine may be added to regorafenib non-responders.
Background & Aims
Differentiation antagonizing non‐protein coding RNA is associated with various types of neoplasms. Hepatitis C virus‐related hepatocellular carcinoma has a high risk of recurrence. ...Here we determined the role of differentiation antagonizing non‐protein coding RNA in hepatitis C virus‐related hepatocarcinogenesis and identified potential therapeutic targets and non‐invasive prognostic markers for long‐term outcome of hepatitis C virus‐related hepatocellular carcinoma after surgical resection.
Methods
Differentiation antagonizing non‐protein coding RNAs relevant to hepatitis C virus‐related hepatocellular carcinoma were identified through comparative RNA‐sequencing of tumour and adjacent non‐tumour (ANT) tissues in a screening set, and were validated using real‐time polymerase chain reaction. Target long non‐coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus‐related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.
Results
We confirmed that differentiation antagonizing non‐protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus‐related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus‐related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non‐protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3‐11.6 and 2.7/1.5‐5.1 respectively).
Conclusions
Differentiation antagonizing non‐protein coding RNA is highly relevant to disease progression of hepatitis C virus‐related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non‐protein coding RNA might serve as a non‐invasive prognostic biomarker for hepatitis C virus‐related hepatocellular carcinoma.
Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma over time. We aimed to explore their impact at the initiation of antiviral therapy on hepatocellular ...carcinoma among chronic hepatitis C (CHC) patients.
A total of 1,281 biopsy-proven CHC patients receiving IFN-based therapy were followed for a mean period of 5.5 years.
The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-sustained virological response (SVR) and SVR patients who were <40 years old (7.7% vs. 0.5%,
= 0.1) but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%,
< 0.001) and >55 years old (15.1% vs. 7.9%,
= 0.03). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients 40 to 55 years old HR/95% confidence intervals (CI), 10.92/3.78-31.56;
< 0.001 and >55 years old (HR/CI, 1.96/1.06-3.63;
= 0.03) but not in patients <40 years old (HR/CI, 2.76/0.41-18.84;
= 0.3). The 5-year cumulative incidence of hepatocellular carcinoma did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%,
= 0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%,
< 0.001) or F4 (33.5% vs. 8.4%,
= 0.002). Compared with SVR, non-SVR was independently predictive of hepatocellular carcinoma in patients with F2-3 (HR/CI, 4.36/2.10-9.03;
< 0.001) and F4 (HR/CI, 3.84/1.59-9.30;
= 0.03) but not in those with F0-1 (HR/CI, 1.53/0.49-4.74;
= 0.47).
Delayed hepatitis C virus clearance for patients with CHC >40 years old or with a fibrosis stage >2 increases the risk of hepatocellular carcinoma over time.
.
Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations such as metabolic abnormalities. The association between chronic hepatitis C (CHC) and uric acid levels has rarely ...been investigated. We aimed to evaluate the levels of serum uric acid in CHC patients.
Three hundred and seventy-three histologically confirmed CHC patients who were scheduled to receive antiviral therapy were consecutively enrolled, and 746 age- and sex-matched uninfected controls were included for comparison. Hyperuricemia was defined as a uric acid level > 7 mg/dL in men and > 6.0 mg/dL in women.
Hyperuricemia was identified in 15.8% of the CHC patients. The uric acid levels did not differ between the CHC patients and the controls (5.54 ± 1.20 mg/dL vs. 5.45 ± 1.45 mg/dL, P = 0.3). Among the 373 CHC patients, the factors associated with hyperuricemia included body mass index (BMI) (OR/CI: 1.13/1.04-1.21, P = 0.003) and estimated glomerular filtration rate (eGFR) (OR/CI: 0.98/0.97-1.00, P = 0.02). Logistic regression analysis revealed that the factors associated with hyperuricemia in male patients included BMI (OR/CI: 1.12/1.05-1.30, P = 0.006) and advanced fibrosis (F3-4) (OR/CI: 0.27/0.09-0.83, P = 0.02), whereas the factors associated with hyperuricemia in female patients included eGFR (OR/CI: 0.97/0.95-0.99, P = 0.02) and diabetes (OR/CI: 3.03/1.11-8.25, P = 0.03). There was a significant decreasing trend of serum uric acid levels with the progression of fibrotic stages among male patients (6.21 ± 1.03 mg/dL 5.82 ± 1.16 mg/dL and 5.44 ± 1.28 mg/dL in stages F0-2, F3, and F4, respectively, trend P = 0.01).
Hyperuricemia was inversely associated with liver disease severity in CHC male patients.
Background & Aims
Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly ...non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC.
Methods
We conducted a retrospective cohort study involving 3878 consecutive HCC patients seen at two tertiary centres in the United States and one in Taiwan from 2004 to 2014. We compared the clinical characteristics, treatment and survival of patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n = 1878).
Results
Cirrhosis was present in 66.8% of the cryptogenic HCC patients, compared with 74.7% of HBV‐related HCC (HBV‐HCC) (P = .001) and 85.9% of HCV‐HCC (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger tumours and at later stages of disease. Five‐year overall survival was 16.3% among cryptogenic HCC patients compared with 31.9% among HBV‐HCC patients and 27.7% among HCV‐HCC patients (P < .001 for both by the log‐rank test). HCC aetiology was not an independent predictor of survival, though ethnicity, cirrhosis status, meeting Milan criteria and treatment allocation were.
Conclusions
Compared with viral HCC patients, those with cryptogenic HCC had lower prevalence of cirrhosis, were diagnosed with larger tumours at more advanced stages of disease, and had poorer overall survival. Additional efforts are needed to identify patients at risk of cryptogenic HCC and to identify cryptogenic HCC at earlier stages of disease.
Background and Aims
Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is ...achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120.
Methods
In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed.
Results
Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (
P
< 0.001 for both) or group D (HBsAg loss:
P
= 0.002; HBsAg seroconversion:
P
< 0.001).
Conclusions
The results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.
Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral ...therapy for chronic hepatitis C.
We conducted a systematic review and meta-analysis searching MEDLINE, SCOPUS through March 2016 and abstracts from recent major liver meetings for primary literature with available hepatitis C treatment rates. Random-effects models were used to estimate effect sizes and meta-regression to test for potential sources of heterogeneity.
We included 39 studies with 476,443 chronic hepatitis C patients. The overall treatment rate was 25.5% (CI: 21.1-30.5%) and by region 34% for Europe, 28.3% for Asia/Pacific, and 18.7% for North America (p = 0.008). On multivariable meta-regression, practice setting (tertiary vs. population-based, p = 0.04), region (Europe vs. North America p = 0.004), and data source (clinical chart review vs. administrative database, p = 0.025) remained significant predictors of heterogeneity. The overall treatment eligibility rate was 52.5%, and 60% of these received therapy. Of the patients who refused treatment, 16.2% cited side effects, 13.8% cited cost as reasons for treatment refusal, and 30% lacked access to specialist care.
Only one-quarter of chronic hepatitis C patients received antiviral therapy in the pre-direct acting antiviral era. Treatment rates should improve in the new interferon-free era but, cost, co-morbidities, and lack of specialist care will likely remain and need to be addressed. Linkage to care should even be of higher priority now that well-tolerated cure is available.
High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients ...and analyze the associated factors of persistent cryoglobulinemia.
Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy.
Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio OR- 4.13, 95% Confidence Interval 95% CI- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy.
The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.
The itemization difference of patient-reported outcome (PRO) in hepatitis patients with different etiologies remains elusive in Asia. We aimed to assess the characteristics and the difference of ...health-related quality of life (HRQoL) in chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) patients.
We conducted the study in an outpatient setting. The 36-Item Short Form Health Survey (SF-36) was completed by the patients upon the initial diagnosis and recruitment for a long-term follow-up purpose. The PRO results were also assessed by disease severity.
There were 244 patients (198 males) of CHB, 54 patients (29 males) of CHC, and 129 patients (85 males) of NAFLD, respectively. CHC patient had the mean score of 67.1 ± 23.3 in physical component summary (PCS) of the SF-36 health survey, which was significantly lower than CHB patients (76.4 ± 19.5), and NAFLD patients (77.5 ± 13.7), respectively (p = 0.001). The significantly lower performance of PCS in CHC patients was mainly attributed to the lower performance in physical functioning and bodily pain components. Higher fibrosis 4 index scores were significantly associated with lower PCS scores in all patient groups. There was no significant difference of mean mental component summary (MCS) between groups. However, NAFLD patients had significantly lower mental health scores than other groups (p = 0.02).
The significant difference of HRQoL exists in hepatitis patients with different etiologies. Disease severity leads to a lower PCS performance.
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