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 this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.
RESULTS: There was a significant reduction in body mass index (median change, Δ = -0.7 kg per m2, p = 0.011), waist circumference (Δ = -3 cm, p = 0.033), systolic blood pressure (Δ = -9 mmHg, p = 0.024), diastolic blood pressure (Δ = -6 mmHg, p = 0.033), fasting blood glucose (Δ = -1.7 mmol/L, p = 0.008), total cholesterol (Δ = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = -19 U/L, p = 0.013), volumetric liver fat fraction (Δ = -7.8%, p = 0.017), steatosis (Δ = -1, p = 0.014), ballooning (Δ = -1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.
CONCLUSION: This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.
METHODS: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy.
RESULTS: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease.
CONCLUSION: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.
METHODS: Adult patients with chronic liver disease who had a liver biopsy and examination with both the M and XL probes were included. Previously defined optimal cut-offs for CAP using the M probe were used for the diagnosis of steatosis grades ≥S1, ≥S2, and S3 (248, 268, and 280 dB/m, respectively).
RESULTS: Data for 180 patients were analyzed (mean age 53.7 ± 10.8 years; central obesity 84.5%; non-alcoholic fatty liver disease 86.7%). The distribution of steatosis grades was S0, 9.4%; S1, 28.3%; S2, 43.9%, and S3, 18.3%. The sensitivity, specificity, positive predictive value, and negative predictive value of CAP using the M/XL probe for the diagnosis of steatosis grade ≥S1 was 93.9%/93.3%, 58.8%/58.8%, 95.6%/95.6%, and 50.0%/47.6%, respectively. These values were 94.6%/94.6%, 41.2%/44.1%, 72.6%/73.6%, and 82.4%/83.3%, respectively, for ≥S2, and 87.9%/87.9%, 27.2%/27.9%, 21.3%/21.5%, and 90.9%/91.1%, respectively, for S3.
CONCLUSION: The same cut-off values for CAP may be used for the M and XL probes for the diagnosis of hepatic steatosis grade.
Methods: This study included patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosed between November 2012 and October 2015. Serum cathepsin D levels were measured using the CatD enzyme-linked immunosorbent assay (USCN Life Science, Wuhan, China) using stored samples collected on the same day of the liver biopsy procedure. The performance of cathepsin D in the diagnosis and monitoring of NASH was evaluated using receiver operating characteristic analysis.
Results: Data for 216 liver biopsies and 34 healthy controls were analyzed. The mean cathepsin D level was not significantly different between NAFLD patients and controls; between NASH and non-NASH patients; and across the different steatosis, lobular inflammation, and hepatocyte ballooning grades. The area under receiver operating characteristic curve (AUROC) of cathepsin D for the diagnosis of NAFLD and NASH was 0.62 and 0.52, respectively. The AUROC of cathepsin D for the diagnosis of the different steatosis, lobular inflammation, and hepatocyte ballooning grades ranged from 0.51 to 0.58. Of the 216 liver biopsies, 152 were paired liver biopsies from 76 patients who had a repeat liver biopsy after 48 weeks. There was no significant change in the cathepsin D level at follow-up compared to baseline in patients who had histological improvement or worsening for steatosis, lobular inflammation, and hepatocyte ballooning grades. Cathepsin D was poor for predicting improvement or worsening of steatosis and hepatocyte ballooning, with AUROC ranging from 0.47 to 0.54. It was fair for predicting worsening (AUROC 0.73) but poor for predicting improvement (AUROC 0.54) of lobular inflammation.
Conclusion: Cathepsin D was a poor biomarker for the diagnosis and monitoring of NASH in our cohort of Asian patients, somewhat inconsistent with previous observations in Caucasian patients. Further studies in different cohorts are needed to verify our observation.
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.
METHOD: We conducted in-depth interviews with stakeholders in Malaysia (N = 44) and Thailand (N = 50), alongside policy document review in both countries. Data were analysed thematically. Results informed development of Systems Thinking diagrams hypothesizing potential intervention points to improve cultural competency, namely via addressing language barriers.
RESULTS: Language ability was a core tenet of cultural competency as described by participants in both countries. Malay was perceived to be an easy language that migrants could learn quickly, with perceived proficiency differing by source country and length of stay in Malaysia. Language barriers were a source of frustration for both migrants and health workers, which compounded communication of complex conditions including mental health as well as obtaining informed consent from migrant patients. Health workers in Malaysia used strategies including google translate and hand gestures to communicate, while migrant patients were encouraged to bring friends to act as informal interpreters during consultations. Current health services are not migrant friendly, which deters use. Concerns around overuse of services by non-citizens among the domestic population may partly explain the lack of policy support for cultural competency in Malaysia. Service provision for migrants in Thailand was more culturally sensitive as formal interpreters, known as Migrant Health Workers (MHW), could be hired in public facilities, as well as Migrant Health Volunteers (MHV) who provide basic health education in communities.
CONCLUSION: Perceptions of overuse by migrants in a health system acts as a barrier against system or institutional level improvements for cultural competency, in an already stretched health system. At the micro-level, language interventions with migrant workers appear to be the most feasible leverage point but raises the question of who should bear responsibility for cost and provision-employers, the government, or migrants themselves.
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: FT and FS examinations were performed on patients with chronic liver disease by two operators, a doctor and a nurse, twice on each patient, at two different time points, independent of each other.
RESULTS: The data for 163 patients with 1304 examinations was analyzed. There was strong correlation between FT and FS for attenuation parameter (Spearman's rho 0.76, p<0.001) and liver stiffness measurement (LSM) (Spearman's rho 0.70, p<0.001). However, FT produced higher value at lower attenuation parameter and LSM, and lower value at higher attenuation parameter and LSM. There was substantial agreement when using 15kPa LSM cut-off, but only moderate agreement when using 10kPa and 20kPa LSM cut-offs and 248dB/m, 268dB/m and 280dB/m attenuation parameter cut-offs. The IQR for attenuation parameter and IQR/median for LSM were significantly lower for FT compared with FS (4dB/m vs 27dB/m, p<0.001, and 10 vs 12, p<0.001, respectively). The intra- and inter-observer reliability of attenuation parameter and LSM using FT and FS were good to excellent with intraclass correlation coefficients 0.89-0.99. FT had shorter examination time (33s vs 47s, p<0.001) and less invalid measurements (0 vs 2, p<0.001).
CONCLUSION: Measurements obtained with FT and FS strongly correlated, but significant differences in their absolute values, consistency, examination time and number of invalid measurements were observed. Either device can be used by healthcare personnel of different backgrounds when sufficiently trained.
METHODS: Cross sectional study. Adult patients diagnosed with HIV infection and had at least one medical encounter in a primary healthcare setting during three years prior to diagnosis were included. We collected data on sociodemographic characteristics, patient characteristics at diagnosis, HIV-related conditions and whether they were subjected to risk assessment and offered HIV testing during the three years prior to HIV diagnosis.
RESULTS: 65 newly HIV-diagnosed patients (male: 92.3%; Malays: 52.4%; single: 66.7%; heterosexual: 41%; homosexual 24.6%; CD4 <350 at diagnosis: 63%). 93.8% were unaware of their HIV status at diagnosis. Up to 56.9% had presented with HIV-related conditions at a primary healthcare facility during the three years prior to diagnosis. Slightly more than half were had risk assessment done and only 33.8% were offered HIV-testing.
CONCLUSIONS: Missed opportunities for HIV-testing was unacceptably high with insufficient risk assessment and offering of HIV-testing. Risk assessment must be promoted and primary care physicians must be trained to recognize HIV-related conditions that will prompt them to offer HIVtesting.
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.
OBJECTIVE: The objective of this article is to evaluate the accuracy of controlled attenuation parameter (CAP) obtained using the XL probe for the estimation of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD).
METHODS: Adult NAFLD patients with a liver biopsy within six months were included and were examined with the FibroScan® M and XL probes. Histopathological findings were reported according to the Non-Alcoholic Steatohepatitis Clinical Research Network Scoring System. Participants who did not have fatty liver on ultrasonography were recruited as controls.
RESULTS: A total of 57 NAFLD patients and 22 controls were included. The mean age of the NAFLD patients and controls was 50.1 ± 10.4 years and 20.2 ± 1.3 years, respectively (p = 0.000). The mean body mass index was 30.2 ± 5.0 kg per m2 and 20.5 ± 2.4 kg per m2, respectively (p = 0.000). The distribution of steatosis grades were: S0, 29%; S1, 17%; S2, 35%; S3, 19%. The AUROC for estimation of steatosis grade ≥ S1, S2 and S3 was 0.94, 0.80 and 0.69, respectively, using the M probe, and 0.97, 0.81 and 0.67, respectively, using the XL probe.
CONCLUSION: CAP obtained using the XL probe had similar accuracy as the M probe for the estimation of hepatic steatosis in NAFLD patients.
METHODS: A questionnaire-based survey using the Simple Lifestyle Indicator Questionnaire (SLIQ) was administered to, and anthropometric measurements were collected from, 494 healthcare workers.
RESULTS: The mean age of the subjects was 32.4±8.4, with a range of 19 to 59 years. The subjects were from the allied health (45.5%), management and professional (25.1%) and executive (29.4%) fields. Overall, 47.4% of the subjects were of normal weight, 30.2% were overweight, 17.2% were obese and 5.2% were underweight. The mean number of working hours per week for the subjects was 47.6±14.0 with the highest working hours found among the management and professional group, followed by the executive and allied health groups. Overall, 39.7% of the healthcare workers worked office hours, 36.6% worked within the shift system, 20.9% worked office hours and were on-call and the remaining 2.8% worked a mixture of office hours and shifts. Based on the SLIQ score, 58.1% were classified as at intermediate risk for CVD, 38.5% were in the healthy category and 3.4% were in the unhealthy category. Factors associated with a healthier lifestyle were being female (Odds Ratio [OR]= 12.1; CI=3.2-46.4), professional (mean score= 6.70), in the allied health group (mean score=7.33) and in the normal BMI group (OR= 9.3, CI= 1.8-47.0).
CONCLUSION: In our study, healthcare workers had an intermediate risk of developing CVD in the future. Thus, there is a need to intervene in the lifestyle factors contributing to CVD.