METHODS AND ANALYSIS: A 2×2 cross-over randomised mechanistic dietary trial will allocate 16 participants with NAFLD to a 2-week either HGI or LGI diet followed by a 4-week wash-out period and then the LGI or HGI diet, alternative to that followed in the first 2 weeks. Baseline and postintervention (four visits) outcome measures will be collected to assess liver fat content (using MRI/S and controlled attenuation parameter-FibroScan), gut microbiota composition (using 16S RNA analysis) and blood biomarkers including glycaemic, insulinaemic, liver, lipid and haematological profiles, gut hormones levels and short-chain fatty acids.
ETHICS AND DISSEMINATION: Study protocol has been approved by the ethics committees of The University of Nottingham and East Midlands Nottingham-2 Research Ethics Committee (REC reference 19/EM/0291). Data from this trial will be used as part of a Philosophy Doctorate thesis. Publications will be in peer-reviewed journals.
TRIAL REGISTRATION NUMBER: NCT04415632.
METHODS: This was a retrospective cohort study involving two hepatobiliary centres from January 1, 2012, to June 30, 2018. Medical records were analysed for sociodemographic, clinical characteristics, laboratory testing, and HCC treatment information. Survival outcomes were examined using the Kaplan-Meier and log-rank test. Prognostic factors were determined using multivariate Cox regression.
RESULTS: A total of 212 patients were included in the study. The median survival time was 22 months. The 1-, 3-, and 5-year survival rates were 64.2%, 34.2%, and 18.0%, respectively. Palliative treatment (adjusted hazard ratio [AHR] = 2.82, 95% confidence interval [CI] 1.75-4.52), tumour size ≥ 5 cm (AHR = 2.02, 95%CI: 1.45-2.82), traditional medication (AHR = 1.94, 95%CI: 1.27-2.98), raised alkaline phosphatase (AHR = 1.74, 95%CI: 1.25-2.42), and metformin (AHR = 1.44, 95%CI: 1.03-2.00) were significantly associated with poor prognosis for HCC survival. Antiviral hepatitis treatment (AHR = 0.54, 95% CI: 0.34-0.87), nonalcoholic fatty liver disease (NAFLD) (AHR = 0.50, 95% CI: 0.30-0.84), and family history of malignancies (AHR = 0.50, 95%CI: 0.26-0.96) were identified as good prognostic factors for HCC survival.
DISCUSSION: Traditional medication, metformin treatment, advanced stage and raised alkaline phosphatase were the poor prognostic factors, while antiviral hepatitis treatment, NAFLD, and family history of malignancies were the good prognostic factors for our HCC cases comorbid with T2D.
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.
METHODS: This was a cross-sectional study on medical students from the University of Malaya. Diagnosis of NAFLD was by transabdominal ultrasonography and following exclusion of significant alcohol intake and other causes of chronic liver disease.
RESULTS: Data of 469 subjects were analyzed (mean age 23.2 ± 2.4 years, 40.3 % male). The racial distribution was: Chinese 53.9 %, Malay 30.5 % and Indian 15.6 %. The overall prevalence of NAFLD was 7.9 %. Subjects with NAFLD were older, had greater BMI and WC, higher SBP and DBP, higher FBS, serum TG and LDL levels, and lower serum HDL level. The prevalence of NAFLD was higher among males compared to females (17.9 % vs. 3.3 %, p
METHODS: The NFS was calculated and LSM obtained for consecutive adult NAFLD patients scheduled for liver biopsy. The accuracy of predicting advanced fibrosis using either modality and in combination were assessed. An algorithm combining the NFS and LSM was developed from a training cohort and subsequently tested in a validation cohort.
RESULTS: There were 101 and 46 patients in the training and validation cohort, respectively. In the training cohort, the percentages of misclassifications using the NFS alone, LSM alone, LSM alone (with grey zone), both tests for all patients and a 2-step approach using LSM only for patients with indeterminate and high NFS were 5.0, 28.7, 2.0, 2.0 and 4.0 %, respectively. The percentages of patients requiring liver biopsy were 30.7, 0, 36.6, 36.6 and 18.8 %, respectively. In the validation cohort, the percentages of misclassifications were 8.7, 28.3, 2.2, 2.2 and 8.7 %, respectively. The percentages of patients requiring liver biopsy were 28.3, 0, 41.3, 43.5 and 19.6 %, respectively.
CONCLUSIONS: The novel 2-step approach further reduced the number of patients requiring a liver biopsy whilst maintaining the accuracy to predict advanced fibrosis. The combination of NFS and LSM for all patients provided no apparent advantage over using either of the tests alone.
METHODS: We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ≥F3).
RESULTS: In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ≥10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS.
CONCLUSIONS: In a retrospective analysis, we found that a 2-step approach using fibrosis scores followed by LSM most accurately detects advanced fibrosis in populations with a low prevalence of advanced fibrosis. However, LSM ≥10 kPa identifies patients with advanced fibrosis with the highest level of accuracy in populations with a high prevalence of advanced fibrosis.
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.