AIMS: To validate the performance of the dual-cutoffs (8/12 kPa) and the proposed algorithm to identify patients with cACLD in three well-characterised Asian nonalcoholic fatty liver disease (NAFLD) cohorts.
METHODS: We included 830 patients with biopsy-proven NAFLD. Liver stiffness was measured using transient elastography (FibroScan).
RESULTS: cACLD was found in 21.8% of patients. Compared with the original Baveno VI elastography criteria (10/15 kPa), the new cutoffs showed a comparable specificity and a higher sensitivity for identifying cACLD. We developed a simplified risk model incorporating age, liver stiffness value, and platelet count, which outperformed liver stiffness measurement alone in two Chinese cohorts (P = 0.001), and was further validated in a Malaysian cohort (P = 0.04). Overall, the "two-step" screening of cACLD improved classification rates from 73.5% by the original dual-cutoffs to 86.7%. Notably, usage of our simplified risk model resulted in significantly lower false-negative rate than the refined screening approach by Papatheodoridi et al (27.1% vs 41.4%; P = 0.01).
CONCLUSIONS: The dual elastography cutoffs of 8 and 12 kPa are more appropriate to identify cACLD in Asian patients with NAFLD. In combination with a simplified risk model in unclassified patients, the two-step approach showed a classification rate of about 85%.
AIMS: We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients.
METHODS: This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula.
RESULTS: MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p
AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients.
METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria).
RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set).
CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.
AIM: To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients.
METHODS: Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort.
RESULTS: We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 109 /L, constituting the Asia-Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%-96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.
CONCLUSIONS: More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy-proven NAFLD patients with majority of patients having NASH.
AIM: To determine how to use CAP in interpreting liver stiffness measurements.
METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP.
RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis.
CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.
AIM: To investigate the efficacy and tolerability of mixed soluble/insoluble fibre vs. psyllium in a randomized double-blind controlled trial.
METHODS: Constipated patients (Rome III) received mixed fibre or psyllium, 5 g b.d., for 4 weeks. Daily symptoms and stool habit were assessed using stool diary. Subjects with ≥1 complete spontaneous bowel movement/week above baseline for ≥2/4 weeks were considered responders. Secondary outcome measures included stool consistency, bowel satisfaction, straining, gas, bloating, taste, dissolvability and quality of life (QoL).
RESULTS: Seventy-two subjects (mixed fibre = 40; psyllium = 32) were enrolled and two from psyllium group withdrew. The mean complete spontaneous bowel movement/week increased with both mixed fibre (P < 0.0001) and psyllium (P = 0.0002) without group difference. There were 30 (75%) responders with mixed fibre and 24 (75%) with psyllium (P = 0.9). Stool consistency increased (P = 0.04), straining (P = 0.006) and bloating scores decreased (P = 0.02) without group differences. Significantly more patients reported improvement in flatulence (53% vs. 25%, P = 0.01) and felt that mixed fibre dissolved better (P = 0.02) compared to psyllium. QoL improved (P = 0.0125) with both treatments without group differences.
CONCLUSIONS: Mixed fibre and psyllium were equally efficacious in improving constipation and QoL. Mixed fibre was more effective in relieving flatulence, bloating and dissolved better. Mixed fibre is effective and well tolerated.
AIM: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy.
METHODS: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method.
RESULTS: After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months.
CONCLUSIONS: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.