Cost-effectiveness study of FIB-4 followed by transient elastography screening strategy for advanced hepatic fibrosis in a NAFLD at-risk population.

BACKGROUND & AIMS: The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies. METHODS: A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. RESULTS: Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold. CONCLUSIONS: Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.

Three segments sampling strategy for the assessment of liver steatosis using magnetic resonance imaging proton density fat fraction.

PURPOSE: This research aims to determine the best liver segments representing the whole-liver fat fraction (FF) in magnetic resonance imaging (MRI)-based measurement of the proton density fat fraction (PDFF). METHOD: This retrospective study included 989 adult subjects who underwent MRI-PDFF from March 2018 to January 2021. Three regions of interest (ROI) were measured and averaged for each hepatic segment and the volume-weighted hepatic FF was calculated. Intrahepatic fat variability was assessed by standard deviation between all ROIs. Univariate and multivariate linear regression analyses were done for the factors associated with intrahepatic fat variability among clinical characteristics, blood parameters and the volume-weighted FF. The arithmetic means of specific hepatic segments that were the closest to the volume-weighted FF were identified in all subjects and those with moderate or severe fatty liver. RESULTS: The volume-weighted FF was 8.18% and variability was 1.33%. Volume-weighted FF was the only associated factor with intrahepatic variability. The arithmetic mean of segments V, VI, and IV was closest to the volume-weighted FF in all subjects and in subjects with moderate or severe fatty liver. CONCLUSIONS: There was considerable heterogeneity in hepatic steatosis between each segment of the liver, and the variability was significantly affected by the volume-weighted FF. The mean hepatic FF from segments V, VI, and IV could be used to estimate the volume-weighted FF of the whole liver, not only in the general population but also in patients with moderate or severe fatty liver.

Role of FIB-4 for reassessment of hepatic fibrosis burden in referral center.

Low cut-off of FIB-4 is a widely used formula to exclude advanced liver fibrosis in primary care centers. However, the range of reported threshold of FIB-4 to rule in advanced fibrosis is too broad across etiologies, and no consensus has been reached. In the present study, we investigated the role of FIB-4 for a reassessment of hepatic fibrosis burden in a referral center. We compared the diagnostic performance of FIB-4 among patients with liver disease of various causes and tried to find an optimal cut-off value for predicting advanced fibrosis. Among 1068 patients, the AUROC of FIB-4 to diagnose advanced fibrosis showed no significant difference among the various etiologies of liver disease, ranging from 0.783 to 0.821. The optimal cut-off value obtained by maximizing Youden's index was 2.68, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for predicting advanced fibrosis were 70.7%, 79.1%, 43.5%, and 92.2%, respectively. The PPV was low in patients with autoimmune disease (6.67%). When we incorporated the new cut-off of FIB-4 into abdominal ultrasound findings, 81% of unnecessary work-ups would be appropriately avoided. In conclusion, the cut-off value of 2.68 showed an acceptable PPV while maintaining a high NPV to predict advanced fibrosis, most etiology except for autoimmune diseases. This result could assist in establishing an appropriate timing to reassess the hepatic fibrosis burden during monitoring in the referral center.

Comparative Assessment and External Validation of Hepatic Steatosis Formulae in a Community-Based Setting.

Several hepatic steatosis formulae have been validated in various cohorts using ultrasonography. However, none of these studies has been validated in a community-based setting using the gold standard method. Thus, the aim of this study was to externally validate hepatic steatosis formulae in community-based settings using magnetic resonance imaging (MRI). A total of 1301 community-based health checkup subjects who underwent liver fat quantification with MRI were enrolled in this study. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC). Non-alcoholic fatty liver disease (NAFLD) liver fat score showed the highest diagnostic performance with an AUROC of 0.72, followed by Framingham steatosis index (0.70), hepatic steatosis index (HSI, 0.69), ZJU index (0.69), and fatty liver index (FLI, 0.68). There were considerable gray zones in three fatty liver prediction models using two cutoffs (FLI, 28.9%; HSI, 48.9%; and ZJU index, 53.6%). The diagnostic performance of NAFLD liver fat score for detecting steatosis was comparable to that of ultrasonography. The diagnostic agreement was 72.7% between NAFLD liver fat score and 70.9% between ultrasound and MRI. In conclusion, the NAFLD liver fat score showed the best diagnostic performance for detecting hepatic steatosis. Its diagnostic performance was comparable to that of ultrasonography in a community-based setting.

Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B.

BACKGROUND: It is controversial whether chronic hepatitis B (CHB) patients have more non-liver comorbidities than non-CHB subjects. AIM: To characterise the demographics, comorbidity and health utilisation of CHB patients in South Korea and compare them to matched controls. METHODS: Using the Health Insurance Review & Assessment Service (HIRA) 2007-2016 database, adult patients with claims for CHB analysed. CHB cases and non-CHB controls matched in a 1:4 ratio using propensity score matching method. RESULTS: The age of CHB patients significantly increased from a mean 46.9 years in 2007 to 52.3 years in 2016. The proportions of persons having both liver-related and non-liver related comorbidities were higher in CHB patients compared to matched controls (dyslipidaemia [37.23% vs 23.77%, P < 0.0001], hypertension [29.39% vs 25.27%, P < 0.0001] chronic kidney disease (CKD) [3.02% vs 1.14%, P < 0.0001] and osteoporosis/fracture [OF] [4.09% vs 3.23%, P < 0.0001]). Approximately 50% of CHB patients had more than one comorbidity among CKD, diabetes, DLP, and OF. The odds of CKD in CHB patients were 1.42 times higher, and the odds of OF in CHB patients were 1.09 times higher than matched controls after adjustment for confounders (P < 0.0001). CONCLUSION: Prevalence of liver as well as non-liver comorbidities in patients with CHB was higher than matched controls and increased over time.

Prevalence of significant hepatic fibrosis using magnetic resonance elastography in a health check-up clinic population.

BACKGROUND: Significant hepatic fibrosis is associated with higher mortality. However, data on the estimated prevalence of liver fibrosis in the general population are scarce. AIM: To use magnetic resonance elastography (MRE) to investigate the prevalence of hepatic fibrosis in a Korean health check-up clinic cohort. METHODS: We enrolled 2170 participants at our health check-up clinic between January 2015 and May 2018, all of whom had MR with chemical shift technique and MRE. The primary objective was to estimate the prevalence of liver fibrosis. For generalisation, sex- and age-standardised prevalence was calculated based on the Korean Statistical Information Service (KOSIS) during the period 2015-2018. RESULTS: The prevalence of F2 (≥3.0 kPa) and F3 (≥3.6 kPa) in the overall cohort was 5.1% and 1.3% respectively (sex- and age-adjusted prevalence of 3.8% and 1.3%). Non-alcoholic fatty liver disease (NAFLD) prevalence (>5% fat fraction) was 27.7% in the average risk population (after excluding alcohol use and viral hepatitis), and the prevalence of significant and advanced fibrosis in NAFLD participants was 8.0% and 1.5% respectively. In participants with diabetes, 12.5% had ≥F2 and 4.3% ≥F3. In participants with NAFLD plus diabetes, 24.1% had ≥F2 and 6.0% ≥F3. On multivariate analysis, only age, insulin, diabetes and fatty liver on MR were independently associated with significant fibrosis. CONCLUSIONS: In a Korean health check-up clinic setting, the prevalence of significant and advanced liver fibrosis was 5.1% and 1.3% (sex- and age-adjusted prevalence of 3.8% and 1.3%). The prevalence of advanced liver fibrosis was five times higher for diabetic participants with NAFLD.

Comparison of conventional sonographic signs and magnetic resonance imaging proton density fat fraction for assessment of hepatic steatosis.

This study correlated conventional ultrasonography (US) signs with the magnetic resonance imaging (MRI) proton density fat fraction (PDFF) to evaluate the diagnostic performance of US signs (alone or combined) to predict presence and degree of hepatic steatosis (HS). Overall, 182 subjects met the study inclusion criteria between February 2014 and October 2016. Four US signs were evaluated independently by two radiologists. MRI PDFF was defined as the average of 24 non-overlapping regions of interest (ROIs) within eight liver segments obtained by drawing three ROIs within each segment. The latter acted as the reference standard to evaluate diagnostic accuracy of the US signs and their combinations. Diagnostic performance of US for HS was assessed using receiver operating characteristic (ROC) curve analyses. There was a strongly positive correlation between some combinations of US signs and PDFF (σ = 0.780, p < 0.001). The sensitivity, specificity, PPV, and NPV were 96.6%, 74.8%, 64.8%, and 97.9%, respectively, determined using abnormal hepatorenal echoes to detect grade 1 or higher HS (area under the ROC curve = 0.875). The sensitivity and NPV for detecting HS with US were good and US may be considered a suitable screening tool for exclusion of HS.

Assessment of risk of complications in cirrhosis using portal thallium scans.

AIM: To investigate the usefulness of a novel thallium scan shunt index for assessing portosystemic shunt-related cirrhotic complications. METHODS: We enrolled 209 chronic hepatitis B-related cirrhosis patients. After rectal thallium instillation, radioactive isotope activity in the heart and liver was measured. The ratio of radiation uptake between the heart and the liver was calculated (the shunt index). This value indicates the degree of portosystemic circulation shunting. Blood tests, serum biochemistry tests, abdominal ultrasonography, gastroscopy and examination of clinical features such as the occurrence of varices, bleeding and hepatic encephalopathy were performed. Multivariate analysis was used to identify independent risk factors for complications. We compared the cumulative incidence rates of complications during the follow-up period. RESULTS: The thallium scan shunt index was significantly higher in the decompensated liver cirrhosis group than in the compensated liver cirrhosis group (0.91 ± 0.39 vs 0.39 ± 0.32, P < 0.001). It was also higher in the varices group, the hepatic encephalopathy group, and the variceal bleeding group than in the control group (P < 0.001). Multivariate analysis showed that the index was an independent risk factor for predicting decompensated liver cirrhosis. When the cut-off value was 0.75, the shunt index had a sensitivity of 82.6%, a specificity of 84%, a positive predictive value of 61.5%, and a negative predictive value of 94.4% in diagnosing decompensated cirrhosis. When the shunt index was greater than 0.75, there was a significant increase in the number of decompensated events. CONCLUSION: The thallium shunt index is a good predictor of cirrhosis-related complications.