Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis.

BACKGROUND AND AIMS: Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up. APPROACH AND RESULTS: From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382). CONCLUSIONS: Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma.

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.

Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR).

BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan.

BACKGROUND/PURPOSE: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.

The Mutation Hotspots at UGT1A Locus May Be Associated with Gilbert's Syndrome Affecting the Taiwanese Population.

Gilbert's syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert's syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert's syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert's syndrome. Hence, this study provides a reference for diagnosing Gilbert's syndrome in the Taiwanese population in the future.

Factors associated with treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive. METHODS: The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end-of-treatment). RESULTS: A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment-experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment-naïve noncirrhotic patients (94.8%) and treatment-experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% ( adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4-261.3, P < .001), followed by GT3/GT2 (aOR/CI: 5.78/2.25-14.9, P = .0003 and aOR/CI: 1.55/1.05-2.29, P = .03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57-7.16, P < .001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67-3.77, P < .001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94-5.58, P < .001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20-5.22, P = .02) and high HCV viral loads (aOR/CI: 2.16/1.57-2.97, P < .001). CONCLUSIONS: DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.

Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients.

BACKGROUND: Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. METHODS: We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. RESULTS: IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893-0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: [Formula: see text] CONCLUSIONS: The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

A GALNT14 rs9679162 genotype-guided therapeutic strategy for advanced hepatocellular carcinoma: systemic or hepatic arterial infusion chemotherapy.

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC patients with distant metastasis. In addition, chemotherapy could achieve complete response in a small proportion of patients. Here, we aimed to investigate whether combination of three previously identified single nucleotide polymorphism (SNP) predictors (GALNT14-rs9679162, WWOX-rs13338697, and rs6025211) could guide our choice between systemic chemotherapy, HAIC, and targeted agents in aHCC patients. A cohort of 237 real-world aHCC patients (171 receiving systemic chemotherapy followed by various anticancer treatments including sorafenib; 66 receiving HAIC) were included for outcome analysis. By combining the three SNP markers with or without addition of two clinical criteria (tumor diameter <8 cm, neutrophils <80%), small groups of patients were found to harbor high complete response rates to systemic chemotherapy (35.3% if the 3-SNP signature alone matched; 60.0% if clinical criteria also matched). Subsequent sorafenib treatment for chemotherapy non-responders was associated with longer overall survival (P < 0.001). In HAIC-treated patients, GALNT14-rs9679162 genotype "GG" was associated with longer overall survival (P = 0.019, median survival > 10.5 months). In conclusion, pre-test for the 3-SNP signature in aHCC patients could identify potential systemic chemotherapy or HAIC responders. Chemotherapy non-responders still benefited from subsequent sorafenib treatment. Accordingly, we propose a roadmap for aHCC patients when chemotherapy or HAIC is to be used.

Real-world experience of elbasvir/grazoprevir in Taiwan: This study was focused on liver and renal adverse effects.

Elbasvir/grazoprevir with or without ribavirin has excellent efficacy and safety for the treatment of hepatitis C virus (HCV) genotype 1 and 4 patients. The real-world experience has been reported but the detailed analysis of liver and renal adverse effects is lacking. This study evaluated the real-world experience relating to the effectiveness and liver/renal safety of elbasvir/grazoprevir in HCV genotype 1 patients with compensated liver disease. In the four medical centres of Chang Gung Medical System, 350 HCV genotype 1 patients with compensated liver disease who were treated with elbasvir/grazoprevir were enrolled. Clinical characteristics and laboratory data were collected. The effectiveness (sustained virologic response 12 weeks after end of treatment, SVR12) and safety were assessed. A consecutive series of 350 patients with a mean age of 68.8 ± 10.0 years old were enrolled. The majority were treatment-naïve (72.3%), genotype 1b (97.7%) and advanced fibrosis/cirrhosis (94.3%). Seventy-nine (22.6%) had hepatocellular carcinoma and 23 (6.6%) had coinfection with hepatitis B. The effectiveness of SVR12 was 94.6% (95% CI: 92.2%-97.0%) in the full analysis set and 99.1% (95% CI: 98.1%-100.1%) in the per-protocol set. There were two relapses and one nonresponder. Seven (2.0%) patients had adverse events resulting in premature discontinuation of treatment. Five of them were considered drug-related. One was due to autoimmune hepatitis. Contrary to previous reports, around 49% of ALT elevation was observed after 8 weeks, and in two patients was due to hepatitis B flares. As to the renal function during the course of therapy, a minor deterioration of eGFR was observed in patients with baseline eGFR ≥60 mL/min/1.73 m2 , but not in those with baseline eGFR <60, <60-30 or <30 mL/min/1.73 m2 . In this real-world data, elbasvir/grazoprevir was effective with few liver/renal adverse effects. One patient developed autoimmune hepatitis.

Decreasing seroprevalence of anti-hepatitis D virus antibodies in the antiviral era with inverse association with hepatitis B virus DNA, Taiwan, 2006 to 2019.

We examined the seroprevalence change of anti-hepatitis D virus (HDV) antibodies in Taiwan from 2006 to 2019. A total of 1147 patients who had chronic hepatitis B virus (HBV) infection were assessed. Of them, 51 (4.4%) were positive for anti-HDV antibodies. Comparison between anti-HDV-positive and negative groups was performed to examine clinical and virological factors related to anti-HDV positivity. It was found that the median HBV-DNA concentration was 1.6 × 105 IU/mL (range, <20-4.5 × 1010 IU/mL) and <20 IU/mL (range, <20-2.0 × 109 IU/mL) for patients with negative and positive anti-HDV antibodies, respectively (P < .001). In addition, a progressive year-to-year decrease of anti-HDV seroprevalence was unveiled. For patients who had HBV-DNA >15 000 IU/mL, the year-to-year (calculated every 2 years) seropositive rates of anti-HDV were 10.0%, 7.9%, 0.7%, 0.3%, 0%, 0%, and 0% (P < .001). For patients who had HBV-DNA <15 000 IU/mL, the year-to-year seropositive rates were 18.6%, 12.8%, 7.8%, 5.0%, 7.3%, 8.0%, and 3.7% (P < .001). In conclusion, seropositive of anti-HDV was inversely associated with HBV-DNA levels. A progressive decrease of anti-HDV seroprevalence was found with no anti-HDV-positive cases detected in high HBV-DNA patient group after 2014.

Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients.

BACKGROUND AND AIMS: Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population. RESULTS: Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor. CONCLUSION: Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.

A community-based study on the application of fatty liver index in screening subjects with nonalcoholic fatty liver disease.

BACKGROUND/PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is now a global liver disease. The fatty liver index (FLI), which is calculated by the equation comprising waist circumference, body mass index (BMI), triglyceride, and gamma glutamyl transpeptidase (GGT), is frequently used for hepatic steatosis evaluation. This study aimed to evaluate the optimal cut-off point of FLI to select subjects for abdominal ultrasonography (US) screening for NAFLD in the community. METHODS: From August 2013 to August 2016, a community-based study was performed in the northeastern region of Taiwan. All subjects participated in a demographic survey, blood testing, and abdominal US. The formula for FLI is: FLI = [e 0.953×loge (TG)+0.139×BMI+0.718×loge (GGT) +0.053×waist circumference-15.745]/[1 + e 0.953×loge (TG)+0.139×BMI+0.718×loge (GGT)+0.053×waist circumference-15.745] × 100. RESULTS: A total of 1371 subjects were included (746 in NAFLD group and 625 in the control group). The mean ages were 57.1 years in the control group and 56.3 years in the NAFLD group. The optimal cut-off points of FLI to discriminate fatty liver by abdominal US were 20 in male and 10 in female (sensitivity 80.3% and 76.1%; specificity 66.9% and 65.5%, respectively). FLI was correlated with the severity of fatty liver by abdominal US, predict fat component percent and NAFLD fibrosis score, especially in the female subjects. CONCLUSION: FLI could be a tool to select subjects for abdominal US in a large community survey. The cut-off point of FLI might be set to 10 for female and 20 for male subjects, to increase the sensitivity for selecting subjects to receive abdominal US.

Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: A population-based cohort study.

Diabetes mellitus may be a risk factor of HCC development in chronic hepatitis B infected patients and affect the all-cause mortality. This study aimed to examine whether DM was associated with the development of HCC with CHB and affected the all-cause mortality. A total of 2966 CHB patients newly diagnosed with DM in 2000 were retrieved from the Longitudinal Cohort of Diabetes Patients database and used propensity scores matching based on age, sex-gender, alcohol-related liver disease and baseline liver cirrhosis to compare with the non-DM patients from the Taiwanese National Health Insurance Research Database. The CHB patients with DM compared to the non-DM had significantly increased (3.3%) risk for HCC development and significantly increased (2.8%) risk of HCC-related mortality. Interestingly, the all-cause mortality was significantly higher in the DM cohort (16.9%) compared to the non-DM cohort (8.2%). In a multivariable transition-specific Cox model to investigate the adjusted hazard ratio of CHB patients with DM or non-DM during the transitions from start to HCC was 1.35; 95% CI (1.16-1.57) and from HCC to death was 1.31; 95% CI (1.06-1.62). All-cause mortality between CHB patients with DM or non-DM during the transitions from start to death was 2.32; 95% CI (1.84-2.92). Taken together, DM is an independent risk factor associated with increasing disease development of HCC, HCC-related mortality and all-cause mortality in CHB patients. This study may provide a clinical strategy for strict DM control in order to reduce the risk of disease development in CHB patients.

Evolution of renal function under direct-acting antivirals treatment for chronic hepatitis C: A real-world experience.

Renal toxicity of direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients has not been well-characterized. The aim of this study was to assess renal safety of DAAs in an Asian CHC patient cohort. Data from CHC patients (n = 1536) treated with DAAs were used in this retrospective study. Serial estimated glomerular filtration rate (eGFR) at pretreatment (1-year prior to treatment), baseline, end of treatment (EOT), and 12 weeks after treatment (SVR12 ) was evaluated. While a significant decrease in eGFR from baseline to EOT (84.8 â†’ 81.8 mL/min/1.73 m2 , P < .001) was observed; subsequently, a slight rise at SVR12 (84.3 mL/min/1.73 m2 ) was also evident. Changes in eGFR after DAA treatment were similar to those seen in PrOD, DCV/ASV and GZP/EBV regimens, except in the SOF-based regimen wherein eGFR remained unchanged from EOT to SVR12 , especially in liver transplant recipients. Multivariate analysis revealed that age >65 years (OR = 1.862, P = .011), baseline eGFR ≥ 60 mL/min/1.73 m2 (OR = 2.684, P = .023), and liver transplant (OR = 3.894, P = .001) were independent risk factors for deteriorating renal function. In conclusion, DAA treatment led to a significant decline in eGFR at EOT but was followed by a slight rise at 12 weeks after treatment. A similar trend was observed with PrOD, DCV/ASV and GZP/EBV, but not in SOF-based regimens. As age >65 years, baseline eGFR ≥ 60 mL/min/1.73 m2 and liver transplantation are significant risk factors for deterioration in renal function, we strongly advice close monitoring of renal function in these populations.

Ages of hepatocellular carcinoma occurrence and life expectancy are associated with a UGT2B28 genomic variation.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive solid tumor. HCC occurred at younger and elder ages were considered driven by different oncogenic mechanisms, and they demonstrated distinct clinical courses. METHODS: A total of 382 HCC patients treated by surgical resections was analyzed. RESULTS: A univariate-multivariate analysis showed that viral etiology (chronic hepatitis B, C) and the UDP glucuronosyltransferase family 2 member B28 (UGT2B28) genomic variant rs2132039 were independently associated with the age at presentation of HCC (all adjusted P < 0.05). An extensive evaluations of clinicalpathological factors showed that the age (Odds ratio [OR], 1.016; 95% confidence interval [CI], 1.001-1.032; adjusted P = 0.037) and ascites (OR, 3.505; CI, 1.358-9.048; adjusted P = 0.010) were two independent factors associated with this genomic variant. The age was 54.1 ± 14.6 years for patients with the "TT" variant type, and 58.2 ± 13.7 years for those with the "Non-TT" variant type. The age disparity was most prominent in alcoholic patients (OR, 1.079; CI, 1.035-1.125; P < 0.001, age of "TT", 49.6 ± 12.2; age of "non-TT", 59.3 ± 10.7). This genomic variant was also associated with age of recurrence (P = 0.025), distant metastasis (P = 0.024) and HCC-related death (P = 0.008) in non-censored patients. CONCLUSIONS: An UGT2B28 genomic variant was indicative of the age of HCC presentation, recurrence, distant metastasis and death.

Is there a sex difference in postoperative prognosis of hepatocellular carcinoma?

BACKGROUND: Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A retrospective study was conducted to evaluate the postoperative prognostic predictors of HCC focusing on sex differences. METHODS: We enrolled 516 consecutive adult patients with HCC (118 women, 398 men), who received surgical resection between January 2000 and December 2007, and were followed-up for >10 years. Clinical and laboratory data together with postoperative outcomes were reviewed. RESULTS: At baseline, female patients had a higher anti-hepatitis C virus antibody prevalence (P = 0.002); lower hepatitis B virus surface antigen prevalence (P = 0.006); less microvascular invasion (P = 0.019); and lower alpha-fetoprotein (P = 0.023), bilirubin (P = 0.002), and alanine transaminase (P = 0.001) levels. Overall, there were no significant sex differences in terms of intrahepatic recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS). However, subgroup analysis showed that women had favorable RFS (P = 0.019) and MFS (P = 0.034) in patients with alpha-fetoprotein ≤ 35 ng/mL, independent of other clinical variables (adjusted P = 0.008 and 0.043, respectively). Additionally, men had favorable OS in patients with prothrombin time (international normalized ratio [INR]) <1.1 (P = 0.033), independent of other clinical variables (adjusted P = 0.042). CONCLUSIONS: Female sex is independently associated with favorable postoperative RFS and MFS in patients with alpha-fetoprotein ≤35 ng/mL, while male sex is independently associated with favorable OS in patients with prothrombin time INR <1.1.

Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: a community-based study.

BACKGROUND: This study aimed to evaluate the association between serum vitamin D levels and nonalcoholic fatty liver disease (NAFLD) parameters, such as metabolic syndrome (MS), inflammatory cytokines (tumor necrosis factor, high sensitive C-reactive protein) and adipokines (adiponectin, leptin). METHODS: From August 2013 to August 2016, a community-based study was performed in the north-eastern region of Taiwan. All subjects received a demographic survey, blood testing and abdominal ultrasonography (US). The vitamin D level was evaluated by quartile divide or used the classification of deficiency (< 20 ng/ml), insufficiency (20-30 ng/ml) and sufficiency (> 30 ng/ml). RESULTS: Subjects were divided into NAFLD group and normal control (subjects number = 564 in each group) following abdominal US study and matching age and gender. The mean age was 57.1 years in NAFLD group and 57.5 in control group. Subjects in NAFLD group had a lower mean vitamin D than those in the control group (28.5 ± 9.5 ng/ml vs. 29.9 ± 10.2 ng/ml, P = 0.018). Subjects with serum vitamin D deficiency or insufficiency had higher odds for MS than those with sufficient vitamin D levels [deficiency vs. sufficiency, adjusted odds ratio (aOR) =1.860 (95% CI = 1.234-2.804), P = 0.003; insufficiency vs. sufficiency, aOR = 1.669 (95% CI = 1.237-2.251), P = 0.001]. Similarly, subjects in the lowest quartile of vitamin D had higher odds for MS than those in the highest quartile of vitamin D (aOR = 2.792, 95% CI = 1.719-4.538, P < 0.001). Vitamin D level was positively correlated with age and male, but negatively correlated with serum leptin level. CONCLUSION: Subjects with low vitamin D level had higher odds for MS, but higher levels of leptin, compared to those with high vitamin D levels.

Development of a fibrosis index including hepatitis B virus basal core promoter A1762T mutation for pretherapeutic evaluation.

BACKGROUND AND AIM: Commonly used non-invasive fibrosis scores usually included serum transaminase levels in the equations, including Aspartate transaminase to Platelet Ratio Index (APRI) and fibrosis-4 (FIB-4). Transaminases fluctuated significantly in chronic hepatitis B patients with exacerbations, leading to unsteady score values. As such, here, we aim to develop a transaminase-free score suitable for pretherapeutic evaluation of fibrosis stages. METHODS: Firstly, 1082 treatment-naïve chronic hepatitis B patients were enrolled and divided into modeling (n = 541) and verification (n = 541) cohorts. Secondly, 265 patients having received liver biopsy, with known Ishak fibrosis stages, were included for independent correlation. RESULTS: Cross-sectional analysis of 1082 patients revealed age-dependent variation of association between virological factors and cirrhosis. A fibrosis score including Anti-hepatitis B e antibody, Basal core promoter (BCP) A1762T mutation, and Platelet count Index (named ABPI) was derived from the modeling cohort. ABPI performed better than APRI and FIB-4 in the verification cohort for identifying cirrhotic patients (comparison of area under the receiver operating characteristic curves: ABPI vs APRI and FIB-4 = 0.785 vs 0.563 [P < 0.001] and 0.700 [P = 0.026], respectively). The performance of ABPI was even better in young (< 40 years old) hepatitis B patients (area under the receiver operating characteristic curves: 0.856 vs 0.402 [P < 0.001] and 0.599 [P = 0.009], respectively). Finally, in the independent cohort of 265 patients with known Ishak fibrosis stages, it was found that ABPI effectively distinguished between Ishak fibrosis stages 3 and > 3 and between 4 and > 4 (P < 0.001 for each). CONCLUSIONS: We developed a transaminase-free fibrosis score (ABPI) utilizing basal core promoter A1762T data, which outperformed APRI and FIB-4.