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Review : Personalized management of cirrhosis by non-invasive tests of liver fibrosis
( Grace Lai-hung Wong ),( Wendell Zaragoza Espinosa ),( Vincent Wai-sun Wong ) 대한간학회 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.3
Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. (Clin Mol Hepatol 2015;21:200-211)
( Won Young Tak ),( Vincent Wai-sun Wong ),( George Boon Bee Goh ),( Pin-nan Cheng ),( Eric J. Lawitz ),( Zobair M. Younossi ),( Raj Vuppalanchi ),( Natalie H. Bzowej ),( Ziad Younes ),( Naim Alkhouri 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Background: Routinely available noninvasive tests of fibrosis (NITs) can be used to identify patients with advanced fibrosis due to NASH, but their performance may vary by race. Our aim was to evaluate the effect of patient race on the diagnostic performance of NITs using data from the global phase 3 STELLAR studies of selonsertib. Methods: The STELLAR studies (NCT03053050 and NCT03053063) enrolled patients with bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH (NAFLD Activity Score [NAS] ≥3). Baseline liver biopsies were centrally read using the NASH Clinical Research Network classification and NITs, including the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness by transient elastography (LS by TE) were measured. The performance of these tests to discriminate advanced (F3-F4) fibrosis by self-reported patient race was evaluated using areas under the receiver operating characteristics curves (AUROCs) with 5-fold cross-validation repeated 100x. Results for White and Asian patients are presented; data for other races (5% of patients screened) are excluded. Results: Among 3202 patients screened for the STELLAR studies with evaluable liver histology, 24% were Asian and 71% were White. The median age was 58 years in both groups; 47% of Asians and 57% of Whites were female (p<0.0001). The prevalence of F3-F4 fibrosis was 67% in Asians and 72% in Whites (p=0.01). AUROCs for each of the NITS for the discrimination of advanced fibrosis were similar between Asian and White patients (Table). In general, literature-based thresholds for the NITs had similar sensitivity and specificity among the specific racial subgroups. Conclusion: In these large, global phase 3 trials, the diagnostic performance of routinely available NITs for the discrimination of advanced fibrosis due to NASH was acceptable and similar between Asian and White patients.
Huapeng Lin,Grace Lai-Hung Wong,Xinrong Zhang,Terry Cheuk-Fung Yip,Ken Liu,Yee Kit Tse,Vicki Wing-Ki Hui,Jimmy Che-To Lai,Henry Lik-Yuen Chan,Vincent Wai-Sun Wong 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.1
Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions: We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.
Application of transient elastography in nonalcoholic fatty liver disease
Xinrong Zhang,Grace Lai-Hung Wong,Vincent Wai-Sun Wong 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.2
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.
( Lilian Yan Liang ),( Hye Won Lee ),( Vincent Wai-sun Wong ),( Terry Cheuk-fung Yip ),( Yee-kit Tse ),( Vicki Wing-ki Hui ),( Grace Chung-yan Lui ),( Henry Lik-yuen Chan ),( Grace Lai-hung Wong ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.3
Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naive chronic hepatitis B (CHB) patients. Methods: Fifteen thousand one hundred eighty-seven treatment-naive adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naive Korean CHB cohort. Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70-0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. Conclusion: A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naive CHB patients with very low risk of HCC to be exempted from HCC surveillance. (Clin Mol Hepatol 2021;27:499-509)
Terry Cheuk-Fung Yip,Fei Lyu,Huapeng Lin,Guanlin Li,Pong-Chi Yuen,Vincent Wai-Sun Wong,Grace Lai-Hung Wong 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.-
Inflammation is the key driver of liver fibrosis progression in non-alcoholic fatty liver disease (NAFLD). Unfortunately, it is often challenging to assess inflammation in NAFLD due to its dynamic nature and poor correlation with liver biochemical markers. Liver histology keeps its role as the standard tool, yet it is well-known for substantial sampling, intraobserver, and interobserver variability. Serum proinflammatory cytokines and apoptotic markers, namely cytokeratin-18, are well-studied with reasonable accuracy, whereas serum metabolomics and lipidomics have been adopted in some commercially available diagnostic models. Ultrasound and computed tomography imaging techniques are attractive due to their wide availability; yet their accuracies may not be comparable with magnetic resonance imaging-based tools. Machine learning and deep learning models, be they supervised or unsupervised learning, are promising tools to identify various subtypes of NAFLD, including those with dominating liver inflammation, contributing to sustainable care pathways for NAFLD.