MATERIAL AND METHODS: This is a cross-sectional study on NAFLD patients who had a liver biopsy and LSM on the same day. The diagnostic performance of the Hepamet fibrosis score was evaluated using the area under the receiver operating characteristic curve (AUROC).
RESULTS: The data for 196 patients were analyzed (mean age 50 ± 11 years old, 50% men, 56.6% Malay, 27.6% Chinese, 15.8% Indian, 67.9% NASH, 15.8% advanced liver fibrosis). The AUROC of Hepamet fibrosis score for the diagnosis of advanced liver fibrosis was 0.85 (95% CI, 0.80 - 0.91). Using the <0.12 and ≥0.47 cut-offs from the original study, the sensitivity, specificity, positive predictive value, negative predictive value, the proportion of indeterminate results and misclassification rate were 81.8%, 91.8%, 47.4%, 98.2%, 32.1% and 6.1%, respectively. Using LSM <10 kPa and ≥15 kPa for the diagnosis of absence and presence of advanced liver fibrosis, respectively, in patients with Hepamet fibrosis score ≥0.47 (i.e., the two-step approach) reduced indeterminate results and misclassification to 16.1% and 3.6%, respectively.
CONCLUSIONS: We found the Hepamet fibrosis score to have good diagnostic accuracy in a population that was largely unrepresented in earlier work and demonstrated its utility in a two-step approach with LSM for the diagnosis of advanced liver fibrosis.
METHODS: A total of 1924 patients with biopsy-proven nonalcoholic fatty liver disease from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all patients. FibroScan-aspartate aminotransferase score (FAST), an elastography-based test for fibrotic NASH, also was available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with a Nonalcoholic Fatty Liver Disease Activity Score of 4 or higher and fibrosis stage of F2 or higher according to the NASH Clinical Research Network scoring system.
RESULTS: The area under the receiver operating characteristic of MACK-3 for fibrotic NASH was 0.791 (95% CI 0.768-0.814). Sensitivity at the previously published MACK-3 threshold of less than 0.135 was 91% and specificity at a greater than 0.549 threshold was 85%. The MACK-3 area under the receiver operating characteristic was not affected by age, sex, diabetes, or body mass index. MACK-3 and FAST results were well correlated (Spearman correlation coefficient, 0.781; P < .001). Except for an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate).
CONCLUSIONS: The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials.
METHODS: A cross-sectional study of consecutive adults in a primary healthcare setting was conducted. Differences in epidemiology, and HRQOL of common FGIDs (functional dyspepsia [FD], irritable bowel syndrome [IBS], functional diarrhea, functional constipation [FC]) between the Rome III and IV criteria were explored.
RESULTS: Among a total of 1002 subjects recruited, the frequency of common FGIDs was 20.7% and 20.9% among subjects based on the Rome III and Rome IV criteria, respectively. The frequency of IBS reduced from 4.0% (Rome III) to 0.8% (Rome IV), while that of functional diarrhea increased from 1.2% (Rome III) to 3.3% (Rome IV). In contrast, there was no significant change in the frequency of FD (7.5% [Rome III] vs 7.6% [Rome IV]) and FC (10.5% [Rome III] vs 11.7% [Rome IV]). Most of the Rome III IBS subjects (52.5%, n = 21) who did not meet Rome IV IBS criteria, fulfilled the criteria for FC, functional diarrhea, FD, or overlap syndrome. Subjects with all FGIDs, regardless of criteria, had more healthcare utilization and lower HRQOL compared to non-FGID controls.
CONCLUSIONS: The Rome IV criteria alter the frequency of IBS and functional diarrhea, but not FD and FC, when compared to the Rome III criteria. Regardless of criteria, FGIDs had a significant impact on healthcare burden and HRQOL.
METHODS: A cross-sectional study of consecutive Asian adults attending a primary healthcare setting was conducted. This study was conducted in 2 phases: The association between BMI and common FGIDs (functional diarrhea/FD, irritable bowel syndrome/IBS, functional diarrhea and functional constipation/FC) was studied initially. The influence of anxiety and depression on BMI and FGIDs was additionally explored in phase 2.
RESULTS: A total of 1002 subjects (median age 32 years, 65.4% females, 90.7% Malay ethnicity, 73.2% higher than secondary level education) were recruited between August 2019 to January 2020. The majority of subjects were obese (39.2%), and had central obesity (51.7%), while 6.1% had metabolic syndrome. The prevalence of FD, IBS, functional diarrhea and FC were 7.5% (n = 75), 4.0% (n = 40), 1.2% (n = 12) and 10.5% (n = 105) respectively, based on the Rome III criteria. Among individual FGIDs, FD subjects had more underweight adults (BMI<18.5kg/m2) compared to controls (13.3% vs 3.5%, P = 0.002) and being underweight remained as an independent association with FD [OR = 3.648 (95%CI 1.494-8.905), P = 0.004] at multi-variate analysis. There were no independent associations between BMI and other FGIDs. When psychological morbidity was additionally explored, anxiety (OR 2.032; 95%CI = 1.034-3.991, p = 0.040), but not depression, and a BMI<18.5kg/m2 (OR 3.231; 95%CI = 1.066-9.796, p = 0.038) were found to be independently associated with FD.
CONCLUSIONS: FD, but not other FGIDs, is associated with being underweight. This association is independent of the presence of anxiety.
METHODOLOGY: Consecutive Asian adults with Rome III diagnosed common FGIDs (functional dyspepsia/FD, IBS and functional constipation/FC) and non-FGID controls were subjected to glucose breath testing, with hydrogen (H2) and methane (CH4) levels determined.
RESULTS: A total of 244 participants (FGIDs n = 186, controls n = 58, median age 45 years, males 36%, Malay ethnicity 76%) were recruited. FGIDs had a higher prevalence trend of SIBO compared to controls (16% FGIDs vs. 10% controls, p = 0.278) with 14% in FD, 18% in IBS and 17% in FC. Compared to controls, SIBO was associated with diarrhoea-predominant IBS (IBS-D) (24% vs. 10%, P = 0.050) but not with other types of FGIDs. IBS-D remained an independent predictor of SIBO (OR = 2.864, 95% CI 1.160-7.071, p = 0.023) but not PPI usage nor history of diabetes (both p > 0.050) at multivariate analysis. Compared to controls, SIBO in IBS-D was associated with an elevated H2 level (≥ 20 ppm from baseline) (18% vs. 3%, p = 0.017), but not CH4 levels (≥ 10 ppm) (9% vs. 7%, p = 0.493). In addition, no difference was found in the prevalence of methane-positive SIBO between chronic constipation (constipation-predominant IBS and FC) compared to controls (9% vs. 7%, P = 0.466).
CONCLUSION: SIBO is prevalent amongst multi-ethnic Asian adults with and without FGIDs. Amongst various FGIDs, only IBS-D is significantly associated with SIBO.
METHODS: A 1085-bp fragment of 23S rRNA domain V from samples of 62 treatment-naïve patients with H. pylori infection was amplified by PCR with newly designed primers, followed by sequencing.
RESULTS: Of the 62 cases, 42 patients were treated with clarithromycin-based triple therapy and 20 patients were treated with amoxicillin and proton pump inhibitor only; both therapies showed successful eradication rates of 70-73.8%. Sequencing analysis detected 37 point mutations (6 known and 31 novel) with prevalences ranging from 1.6% (1/62) to 72.6% (45/62). A2147G (aka A2143G) appears to be associated with a low eradication rate [40% (2/5) failure rate and 13.3% (6/45) treatment success rate], supporting its role as a clinically significant point mutation. T2186C (aka T2182C) was found in 71.1% (32/45) and 80% (4/5) of treatment success and failure cases, respectively, suggesting that the mutation is clinically insignificant. The eradication success rate in patients with the novel T2929C mutation was decreased three-fold (6.7%; 3/45) compared with the failure rate (20%; 1/5), suggesting that it may play an important role in clarithromycin resistance, thus warranting further study.
CONCLUSION: This study identified multiple known and novel mutations in 23S rRNA domain V through direct sequencing. Molecular detection of clarithromycin resistance directly on biopsies offers an alternative to conventional susceptibility testing.
AIM: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH.
METHODOLOGY: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). MACK-3 cut-offs ≤0.134 and ≥0.550 were used to predict absence and presence of fibrotic NASH, respectively. Histopathological examination of liver biopsy specimen was reported according to the NASH Clinical Research Network Scoring System.
RESULTS: Data for 196 subjects were analysed. MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18. MACK-3 was good for diagnosis of active NASH (AUROC 0.81) and was superior to other blood fibrosis tests. The overall accuracy, percentage of subjects in grey zone, sensitivity, specificity, positive predictive value and negative predictive value of MACK-3 for diagnosis of fibrotic NASH was 79.1%, 46.9%, 100%, 43.8%, 43.1% and 100%, respectively, while for diagnosis of active NASH was 90.0%, 39.3%, 84.2%, 81.4%, 88.9% and 74.5%, respectively.
CONCLUSION: MACK-3 is promising as a non-invasive test for active NASH and fibrotic NASH and may be useful to identify patients who need more aggressive intervention.
METHODS: This is a single-centre prospective study of a well-characterized cohort of MAFLD patients who underwent liver biopsy and followed every 6-12 months for adverse clinical outcomes.
RESULTS: The data for 202 patients were analyzed [median age 55.0 (48.0-61.3) years old; male, 47.5%; obese, 88.6%; diabetes mellitus, 71.3%; steatohepatitis, 76.7%; advanced fibrosis, 27.2%]. The median follow-up interval was 7 (4-8) years. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality was 0.43, 2.03, 0.60 and 0.60 per 100 person-years of follow-up, respectively. Liver-related events were only seen in patient with advanced fibrosis at 9.1% vs 0% in patient without advanced liver fibrosis (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: A cross-sectional study of consecutive adult patients who underwent glucose hydrogen breath test was conducted. Factors associated with SIBO were evaluated. Symptom severity and HRQoL of IBS patients with and without SIBO were compared. The independent factors associated with severe IBS were explored.
RESULTS: A total of 160 patients were included (median age 40 years, males 31.3%). IBS was present among 53.8% of subjects, with 33.8% having diarrhea-predominant IBS (IBS-D). SIBO was diagnosed in 22.5% of the study population. Patients with SIBO were more commonly diagnosed with IBS-D than those without (50.0% vs 29.0%, P = 0.019). Severe IBS was associated with SIBO (36.4% vs 15.6%, P = 0.043). SIBO was associated with poorer HRQoL (Euroqol five-dimensional utility score: 0.73 vs 0.80, P = 0.024). SIBO (44.4% vs 20.6%, P = 0.043), anxiety (77.8% vs. 39.7%, P = 0.004), and depression (50.0% vs 19.1%, P = 0.011) were associated with severe IBS in the univariate analysis. However, SIBO was the only independent factor associated with severe IBS in the multivariate analysis (adjusted odds ratio 3.83, 95% confidence interval CI 1.02-14.34, P = 0.046).
CONCLUSIONS: There was a significant association between IBS-D and SIBO. The coexistence of SIBO had a significant negative impact on IBS patients.