Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.
Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score
METHODS: In the multi-centre controlled attenuation parameter (CAP)-Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia. Physical activity was assessed using the International Physical Activity Questionnaire.
RESULTS: A total of 555 patients were included in the final analysis (mean age 54.5 ± 11.2 years, 54.1% men and median liver stiffness 6.7 kPa). More patients from mainland China (27.4%) and Taipei (25.0%) were smokers. Modest drinking was more common in Taiwan (25.0%) and Hong Kong (18.2%); only 1.3% had binge drinking. Majority of patients drank coffee (64.0%) and tea (80.2%), with varying amounts and durations in different regions. Soft drinks consumption was most common in Singapore (62.2%) and Malaysia (57.7%). Only 29.7% of patients met the Physical Activity Guidelines Recommendations, with no major differences across regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity, and sitting time was an independent factor associated with high CAP. Tea and coffee consumption were independently associated with high CAP and liver stiffness, respectively.
CONCLUSIONS: Despite some heterogeneity, unhealthy lifestyle and physical inactivity are common across Asian regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity. Healthcare providers may use the comparative data to identify areas of deficiency.
METHODS: This was an international, multicenter, prospective, randomized controlled study. After providing informed consent, consecutive adult patients referred for EUS-FNTA for solid lesions larger than 2 cm were randomized to a MOSE arm or to a conventional arm without ROSE. A designated cytopathologist from each center performed all cytopathological examinations for that center and was blinded to the randomization results. The primary outcome measure was the diagnostic yield, and the secondary outcomes included sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and the rate of procedure-related complications.
RESULTS: 244 patients (122 conventional, 122 MOSE) were enrolled during the study period. No significant differences between the two arms were found in procedure time or rate of procedure-related adverse events. The diagnostic yield for the MOSE technique (92.6 %) was similar to that for the conventional technique (89.3 %; P = 0.37), with significantly fewer passes made (median: conventional 3, MOSE 2; P
METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.
RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P
METHODS: Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6 months prior to liver biopsy. F3-F4 fibrosis was excluded using LSM cut-off of 7.9 kPa.
RESULTS: A total of 136 patients were recruited. Eighty-five percent (115/136) of patients had high baseline LSM (≥ 7.9 kPa). Among them, 25% (29/115) had low repeat LSM (
METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection.
RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity.
DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.
AIM: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).
METHODS: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.
RESULTS: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).
CONCLUSION: The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.
METHODS: Consecutive biopsy-proven NAFLD patients (n = 191) and healthy controls (n = 188) were enrolled and genotyped for HLA-DQA1 and HLA-DQB1 alleles using the sequence-specific oligonucleotide-polymerase chain reaction method.
RESULTS: No association was found between the HLA alleles and NAFLD or NASH in a case-control setting. Nevertheless, among NAFLD patients, the frequency of HLA-DQB1*06 allele was significantly the lowest in NASH with significant fibrosis (10.4%) and approximately similar for NASH without significant fibrosis (22.9%) and NAFL (22.5%) (P = 0.004). It is noteworthy that the association remains significant after correction for multiple comparisons (Pc = 0.04). Multivariate analysis revealed that HLA-DQB1*06 allele is also associated with fibrosis score (P = 0.001); the result remains significant after correction for multiple comparisons.
CONCLUSION: These findings suggest that HLA-DQB1*06 is associated with lower fibrosis score in NAFLD patients.
METHODS: We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis.
RESULTS: Of the 1008 patients, 175 were elderly [age 64 (62-67) years], who were matched with 525 non-elderly patients [46 (36-54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p
METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009.
FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0.
INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease.
FUNDING: Echosens and UK National Institute for Health Research.
METHODS: We performed a prospective study of consecutive adults with NAFLD who were scheduled for a liver biopsy at a tertiary hospital in Malaysia. Patients underwent VLFF and CAP measurements on the same day as their liver biopsy. Histopathology analyses of liver biopsy specimens were reported according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Stereologic analysis was performed using grid-point counting method combined with the Delesse principle.
RESULTS: We analyzed data from 97 patients (mean age 57.0 ± 10.1 years; 44.33% male; 91.8% obese; 95.9% centrally obese). Based on histopathology analysis, the area under receiver operating characteristic curve (AUROC) for VLFF in detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.65 (P < .001). Based on stereological analysis, the AUROC for VLFF for detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.63, (P = .002); for identification of steatosis grade S3, the AUROC for VLFF was 0.92 and for CAP the AUROC was 0.68 (P < .001).
CONCLUSIONS: In a prospective study of patients with NAFLD undergoing liver biopsy analysis, we found VLFF to more accurately determine grade of hepatic steatosis than CAP.
METHODS: Consecutive NAFLD patients attending five clinics in Asia were included in this study. The 10-year cardiovascular disease risk was calculated based on the Framingham Heart Study, and patients were categorized as moderate, high, or very high risk for cardiovascular disease on the basis of the American Association of Clinical Endocrinologist 2017 Guidelines. The low-density lipoprotein cholesterol treatment goal for each of the risk groups was 2.6, 2.6, and 1.8 mmol/L, respectively.
RESULTS: The data for 428 patients were analyzed (mean age 54.4 ± 11.1 years, 52.1% male). Dyslipidemia was seen in 60.5% (259/428), but only 43.2% (185/428) were on a statin. The percentage of patients who were at moderate, high, and very high risk for cardiovascular disease was 36.7% (157/428), 27.3% (117/428), and 36.0% (154/428), respectively. Among patients who were on a statin, 58.9% (109/185) did not achieve the treatment target. Among patients who were not on a statin, 74.1% (180/243) should be receiving statin therapy. The percentage of patients who were not treated to target or who should be on statin was highest among patients at very high risk for cardiovascular disease at 79.6% (78/98) or 94.6% (53/56), respectively.
CONCLUSION: This study highlights the suboptimal treatment of dyslipidemia and calls for action to improve the treatment of dyslipidemia in NAFLD patients.