Diagnostic and prognostic performance of the SAFE score in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The steatosis-associated fibrosis estimator (SAFE) score was developed to detect clinically significant liver fibrosis in patients with NAFLD in the United States. We compare the performance of the SAFE score and other non-invasive tests to diagnose liver fibrosis and to correlate the scores with liver-related outcomes in patients with NAFLD in Hong Kong. METHODS: This was a retrospective cohort study involving two data sets. The first cohort was a biopsy cohort of NAFLD patients (n = 279), and the second was a territory-wide cohort of NAFLD patients (n = 4603) retrieved from a territory-wide electronic healthcare database in Hong Kong. RESULTS: In detecting significant fibrosis, liver stiffness measured by transient elastography had the highest area under the receiver operating characteristic curve (AUROC) (.844), followed by SAFE score (.773). SAFE score had the highest AUROC among blood-based algorithms (.773 vs. .746 for FIB-4, .697 for APRI). Based on cut-off values of SAFE score (0 and 100 points), 854 (18.6%), 1596 (34.6%) and 2153 (46.8%) were in the low-, intermediate- and high-risk groups, respectively, in the territory-wide cohort. Six (.7%), 15 (.9%) and 59 (2.7%) developed liver-related events in those three groups respectively. Among patients who had liver-related events at 5 years, using the high cut-off, SAFE score could predict 84.9% of patients accurately, compared to 40.9% for FIB-4 and 27.2% for APRI. CONCLUSION: The SAFE score performed well and better than other blood-based markers in diagnosing significant fibrosis and predicting liver-related events in Asian patients with NAFLD.

Performance of continuous controlled attenuation parameter and liver stiffness measurement by the novel SmartExam in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: FibroScan® Expert 630 and FibroScan® Mini+430 are novel vibration-controlled transient elastography devices equipped with the same SmartExam software, which allows continuous measurement of controlled attenuation parameter (CAP) during the entire examination. This study aims to compare the CAP variabilities and the quantification for liver fibrosis and steatosis between the conventional FibroScan and the SmartExam-equipped machines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This retrospective study included 118 patients with biopsy-proven MASLD who underwent liver biopsy at two tertiary centres between 2021 and 2023. Liver stiffness and steatosis measurements were performed using both FibroScan machines and M and XL probes for each individual. Liver histology was used as the reference standard for liver fibrosis and steatosis staging. RESULTS: Standard deviations of continuous CAP (cCAP) were significantly lower than those of CAP for all probes (p < .0001). CAP variability was significantly associated with body mass index (p < .01), probe selection (p < .001) as well as the random effect of centre. Only the effect of probe selection (p < .001) was significantly associated with cCAP variability. No significant difference was found in the performance of staging liver fibrosis and steatosis between two types of machines at the same cut-offs. CONCLUSIONS: The SmartExam-based VCTE reduces the variability of CAP measurement and achieves a similar accuracy as the FibroScan 502 device for the estimation of both hepatic steatosis and fibrosis. Future studies should determine if cCAP is a better tool to monitor changes in steatosis than the original CAP.

Secular trend of treatment uptake in patients with chronic hepatitis B: A territory-wide study of 135 395 patients from 2000 to 2017.

BACKGROUND AND AIMS: The uptake of antiviral treatment for patients with chronic hepatitis B (CHB) has been suboptimal. We aimed to determine the secular trend of treatment uptake in the territory-wide CHB cohort in Hong Kong from 2000 to 2017 and the factors for no treatment despite fulfilling treatment criteria. METHODS: Chronic hepatitis B patients under public clinics and hospitals were identified through electronic medical records. The treatment indications were defined according to the Asian-Pacific guidelines published at the time of patients' first appearance in four periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. RESULTS: There were 135 395 CHB patients were included; 1493/12472 (12.0%), 7416/43426 (17.1%), 10 129/46559 (21.8%), 8051/32 938 (24.4%) patients fulfilled treatment criteria in the four periods, respectively. The treatment uptake rate increased with time: 35.1%, 43.4%, 60.2%, and 68.6% respectively. High fibrosis indices (APRI, FIB-4, and Forns indices) appeared to be the main factors for treatment indication in non-cirrhotic patients, with over 90% fulfilling treatment criteria due to high fibrosis indices alone. Of those fulfilling treatment criteria by high fibrosis indices, less than 60% of patients (25.2%, 36.1%, 46.0%, and 58.9%, respectively) had antiviral treatment initiated. Normal platelet count (odds ratio 0.42, P < 0.001) was the independent factor associated with not initiating antiviral treatment in patients fulfilling treatment criteria. CONCLUSIONS: Treatment uptake rates have been increasing over time. Normal platelet count, which reflects less advanced liver disease, precludes patients from receiving antiviral treatment even if treatment indication is fulfilled. Hence, the importance to identify non-cirrhotic patients with significant liver fibrosis should be emphasized.

The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg-negative chronic hepatitis B.

BACKGROUND: The rates of hepatitis B surface antigen (HBsAg) seroclearance after stopping nucleos(t)ide analogues (NA) in European (19% in 2 years) and Asian (13% in 6 years) patients with chronic hepatitis B (CHB) vary dramatically. We evaluated the incidence of hepatitis flare and HBsAg seroclearance in hepatitis B e antigen (HBeAg)-negative Chinese CHB patients who had stopped NA. METHODS: This was a territory-wide retrospective study in Hong Kong. We identified HBeAg-negative CHB patients from January 2000 to December 2017 who had stopped NA treatment for more than 3 months. Hepatitis flare was defined as ALT >2×ULN. RESULTS: The 1076 patients were predominantly middle-aged men (mean age 52 years, male 74.8%) when starting NA; they stopped NA after 82 ± 35 months of treatment. At 44.3 ± 24.6 months after stopping NA, 147 (13.6%) patients had hepatitis flare, which led to resumption of NA; whereas 77 (7.2%) patients had flare but did not resume NA. Decompensation occurred in 7/914 (0.8%) patients. A total of 695 (64.6%) patients remained on NA treatment at the last visit. Eleven patients had achieved HBsAg seroclearance (6 of them had hepatitis flare and 1 of these 6 patients achieved HBsAg seroclearance after NA was restarted). Hepatic events developed in 75/695 (10.8%) patients who had NA resumed vs 43/381 (11.3%) patients who did not resume NA (P = .677). CONCLUSIONS: Hepatitis flare and retreatment were common in HBeAg-negative CHB patients who stopped NA treatment; whereas HBsAg seroclearance rarely occurred. Stopping NA to achieve functional cure should not be recommended at this moment.

Clinical outcomes and management of patients with chronic hepatitis B and liver stiffness measurement in the grey zone.

BACKGROUND: A significant number of patients have liver stiffness measurements in the grey zone where liver biopsy is recommended. AIMS: To study chronic hepatitis B patients with initial liver stiffness measurements in the grey zone with regards to rates of liver biopsy, repeat liver stiffness measurements and outcomes. METHODS: Consecutive chronic hepatitis B patients who underwent transient elastography from August 2006 to July 2017 were retrospectively studied. Liver-related events were defined as hepatocellular carcinoma or cirrhotic complications. Grey zone was defined as liver stiffness measurements: 6.1-9.0 kPa (normal ALT) or 7.6-12.0 kPa (ALT 1-5 × upper limit of normal) on M-probe and 6.9-10.0 kPa on XL-probe. RESULTS: Of the 3212 patients analysed, 837 (26%) had initial liver stiffness measurements in grey zone. Only 3.6% of grey zone patients proceeded to liver biopsy within 6 months of transient elastography, of which 33% had METAVIR F3-4 fibrosis. Repeat liver stiffness measurements was performed in 44% of grey zone patients. Liver biopsy and repeat liver stiffness measurements prompted change in management in 47% and 31% of patients respectively. Independent predictors for liver-related events in grey zone patients included increased age, low albumin and low platelet count. Liver-related events rates were increased (9%-17%) in patients with METAVIR > F2 fibrosis on biopsy or repeat liver stiffness measurements which did not improve. CONCLUSIONS: Chronic hepatitis B patients with initial liver stiffness measurements in the grey zone rarely proceed to a clarifying liver biopsy which would reveal advanced fibrosis or cirrhosis in one-third of patients. Both liver biopsy and repeat liver stiffness measurements in grey zone patients have clinical utility in prompting changes in management and providing prognostic information.