Noninvasive risk assessment of hepatic decompensation in patients with hepatitis B virus-related liver cirrhosis.

BACKGROUND AND AIM: Hepatic decompensation is a major complication of liver cirrhosis. We validated the predictive performance of the newly proposed CHESS-ALARM model to predict hepatic decompensation in patients with hepatitis B virus (HBV)-related cirrhosis and compared it with other transient elastography (TE)-based models such as liver stiffness-spleen size-to-platelet (LSPS), portal hypertension (PH), varices risk scores, albumin-bilirubin (ALBI), and albumin-bilirubin-fibrosis-4 (ALBI-FIB-4). METHODS: Four hundred eighty-two patients with HBV-related liver cirrhosis between 2006 and 2014 were recruited. Liver cirrhosis was clinically or morphologically defined. The predictive performance of the models was assessed using a time-dependent area under the curve (tAUC). RESULTS: During the study period, 48 patients (10.0%) developed hepatic decompensation (median 93 months). The 1-year predictive performance of the LSPS model (tAUC = 0.8405) was higher than those of the PH model (tAUC = 0.8255), ALBI-FIB-4 (tAUC = 0.8168), ALBI (tAUC = 0.8153), CHESS-ALARM (tAUC = 0.8090), and variceal risk score (tAUC = 0.7990). The 3-year predictive performance of the LSPS model (tAUC = 0.8673) was higher than those of the PH risk score (tAUC = 0.8670), CHESS-ALARM (tAUC = 0.8329), variceal risk score (tAUC = 0.8290), ALBI-FIB-4 (tAUC = 0.7730), and ALBI (tAUC = 0.7451). The 5-year predictive performance of the PH risk score (tAUC = 0.8521) was higher than those of the LSPS (tAUC = 0.8465), varices risk score (tAUC = 0.8261), CHESS-ALARM (tAUC = 0.7971), ALBI-FIB-4 (tAUC = 0.7743), and ALBI (tAUC = 0.7541). However, there was no significant difference in the predictive performance among all models at 1, 3, and 5 years (P > 0.05). CONCLUSIONS: The CHESS-ALARM score was able to reliably predict hepatic decompensation in patients with HBV-related liver cirrhosis and showed similar performance to the LSPS, PH, varices risk scores, ALBI, and ALBI-FIB-4.

Global burden of primary liver cancer and its association with underlying aetiologies, sociodemographic status, and sex differences from 1990-2019: A DALY-based analysis of the Global Burden of Disease 2019 study.

BACKGROUND/AIMS: Global distribution of dominant liver cancer aetiologies has significantly changed over the past decades. This study analyzed the updated temporal trends of liver cancer aetiologies and sociodemographic status in 204 countries and territories from 1990 to 2019. METHODS: The Global Burden of Disease 2019 report was used for statistical analysis. In addition, we performed stratification analysis to five quintiles using sociodemographic index and 21 geographic regions. RESULTS: The crude numbers of liver cancer disease-adjusted life years (DALYs) and deaths significantly increased during the study period (DALYs; 11,278,630 in 1990 and 12,528,422 in 2019, deaths; 365,215 in 1990 and 484,577 in 2019). However, the Age-standardized DALY and mortality rates decreased. Hepatitis B virus (HBV) remains the leading cause of liver cancer DALYs and mortality, followed by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (NASH/NAFLD). Although Age-standardized DALY and mortality rates of liver cancer due to HBV and HCV have decreased, the rates due to alcohol consumption and NASH/NAFLD have increased. In 2019, the population of the East Asia region had the highest Age-standardized DALY and mortality rates, followed by high-income Asia-Pacific and Central Asia populations. Although East Asia and high-income Asia-Pacific regions showed a decrease during the study period, Age-standardized DALY rates increased in Central Asia. High-income North American and Australasian populations also showed a significant increase in Age-standardized DALY. CONCLUSION: Liver cancer remains an ongoing global threat. The burden of liver cancer associated with alcohol consumption and NASH/NAFLD is markedly increasing and projected to continuously increase.

Risk assessment of hepatocellular carcinoma and liver-related events using ultrasonography and transient elastography in patients with chronic hepatitis B.

Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13 kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n = 5474, 58.9%) with a mean age of 47.5 years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n = 1595) and 13.2% (n = 1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n = 1740). During follow-up (median: 60.0 months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p < .001). Cirrhosis assessed using US and TE was a major predictor of HCC and liver-related event development in patients with CHB. Cirrhosis assessed using TE seemed better in predicting HCC or liver-related events than using US, when cirrhosis diagnosis was discordant by US and TE.

Longitudinal assessment of alpha-fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis.

Background/aims: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC), and the surveillance of patients with cirrhosis is, therefore, highly recommended. However, the role of alpha-fetoprotein (AFP) in HCC surveillance is controversial. The aim of this study was to determine the role of AFP in HCC surveillance among patients with cirrhosis.Methods: The study population consisted of 392 patients with cirrhosis. Ultrasound (US) and laboratory tests including AFP were regularly performed to detect HCC development. The cutoff level of AFP for suspicion of HCC was 7 ng/mL.Results: During the median follow-up period of 4.7 (interquartile range, 3.4-5.6) years, HCC developed in 64 (16.3%) patients. Their mean age was 53.6 years, and they were predominantly male (63.5%). For the detection of HCCs, the sensitivity and specificity of US were 56.3% and 100%, respectively. The sensitivity and specificity of AFP were 62.5% and 94.5%, respectively. Using US and AFP in combination increased the sensitivity of surveillance to 89.1% with a specificity of 94.5%. Mean AFP levels were significantly higher in patients with than without HCC at the time of HCC diagnosis, at 6 months and 12 months before the diagnosis. The area under the receiver operating characteristic curve of AFP was highest at the time of HCC diagnosis (0.867), and also was acceptable at 6 months (0.823) and 12 months (0.792) before the diagnosis.Conclusions: These results suggest the complementary use of AFP and US to improve the effectiveness of HCC surveillance in patients with cirrhosis.

Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B.

BACKGROUND/AIMS: A risk prediction model for the development of hepatocellular carcinoma (HCC) from indeterminate nodules detected on computed tomography (CT) (RadCT score) in patients with chronic hepatitis B (CHB)-related cirrhosis was proposed. We validated this model for indeterminate nodules on magnetic resonance imaging (MRI). METHODS: Between 2013 and 2016, Liver Imaging Reporting and Data System (LI-RADS) 2/3 nodules on MRI were detected in 99 patients with CHB. The RadCT score was calculated. RESULTS: The median age of the 72 male and 27 female subjects was 58 years. HCC history and liver cirrhosis were found in 47 (47.5%) and 44 (44.4%) patients, respectively. The median RadCT score was 112. The patients with HCC (n=41, 41.4%) showed significantly higher RadCT scores than those without (median, 119 vs. 107; P=0.013); the Chinese university-HCC and risk estimation for HCC in CHB (REACH-B) scores were similar (both P>0.05). Arterial enhancement, T2 hyperintensity, and diffusion restriction on MRI were not significantly different in the univariate analysis (all P>0.05); only the RadCT score significantly predicted HCC (hazard ratio [HR]=1.018; P=0.007). Multivariate analysis showed HCC history was the only independent HCC predictor (HR=2.374; P=0.012). When the subjects were stratified into three risk groups based on the RadCT score (<60, 60-105, and >105), the cumulative HCC incidence was not significantly different among them (all P>0.05, log-rank test). CONCLUSION: HCC history, but not RadCT score, predicted CHB-related HCC development from LI-RADS 2/3 nodules. New risk models optimized for MRI-defined indeterminate nodules are required.

Feasibility of dynamic risk assessment for patients with repeated trans-arterial chemoembolization for hepatocellular carcinoma.

BACKGROUND: Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. METHODS: A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. RESULTS: Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively). CONCLUSIONS: All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE.

Predictors of Discordance in the Assessment of Skeletal Muscle Mass between Computed Tomography and Bioimpedance Analysis.

Computed tomography (CT) and bioimpedance analysis (BIA) can assess skeletal muscle mass (SMM). Our objective was to identify the predictors of discordance between CT and BIA in assessing SMM. Participants who received a comprehensive medical health check-up between 2010 and 2018 were recruited. The CT and BIA-based diagnostic criteria for low SMM are as follows: Defined CT cutoff values (lumbar skeletal muscle index (LSMI) <1 standard deviation (SD) and means of 46.12 cm²/m² for men and 34.18 cm²/m² for women) and defined BIA cutoff values (appendicular skeletal muscle/height² <7.0 kg/m² for men and <5.7 kg/m² for women). A total of 1163 subjects were selected. The crude and body mass index (BMI)-adjusted SMM assessed by CT were significantly associated with those assessed by BIA (correlation coefficient = 0.78 and 0.68, respectively; p < 0.001). The prevalence of low SMM was 15.1% by CT and 16.4% by BIA. Low SMM diagnosed by CT was significantly associated with advanced age, female gender, and lower serum albumin level, whereas low SMM diagnosed by BIA was significantly associated with advanced age, female gender, and lower BMI (all p < 0.05). Upon multivariate analysis, age >65 years, female and BMI <25 kg/m² had significantly higher risks of discordance than their counterparts (all p < 0.05). We found a significant association between SMM assessed by CT and BIA. SMM assessment using CT and BIA should be interpreted cautiously in older adults (>65 years of age), female and BMI <25 kg/m².

Multicenter Retrospective Risk Assessment of Esophageal Variceal Bleeding in Patients with Cirrhosis: An Acoustic Radiation Force Impulse Elastography-Based Prediction Model.

Background/Aims: Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis. Methods: The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI-spleen diameter-to-platelet ratio scores (ASPS) were calculated. Results: The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×109/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047). Conclusions: ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.

Risk Assessment of Hepatocellular Carcinoma Using Transient Elastography Vs. Liver Biopsy in Chronic Hepatitis B Patients Receiving Antiviral Therapy.

Liver stiffness (LS) assessed using transient elastography (TE) can assess the risk of developing hepatocellular carcinoma (HCC). We evaluated whether TE, when compared with histological data as a reference standard, can predict the risk of HCC development in chronic hepatitis B (CHB) patients starting antiviral therapy.Observational cohort database of 381 patients with CHB who underwent liver biopsy (LB) and TE were reviewed. All patients underwent surveillance for HCC development using ultrasonography and alpha-fetoprotein.During the median follow-up period of 48.1 (interquartile range 30.3-69.3) months, HCC developed in 34 (8.9%) patients. In patients with HCC development, age, proportion of diabetes mellitus, histological fibrosis stage, and LS value were significantly higher than those in patients without (all P <0.05). The cumulative incidence rates of HCC increased significantly in association with elevated LS value in 3 stratified groups (LS value <8, 8-13, and >13 kPa; log-rank test, P <0.001), and with higher histological fibrosis stage in 3 stratified groups (F0-2, F3, and F4; log-rank test, P <0.001). On multivariate analysis, along with age, LS value was an independent predictor of HCC development (hazard ratio 1.041, P <0.001), whereas histological staging was not (P >0.05).TE predicted HCC development independently in patients with CHB starting antiviral therapy. However, further investigation is needed to determine whether the current surveillance strategy can be optimized based on the LS value at the time of starting antiviral therapy.

Red cell volume distribution width-to-platelet ratio in assessment of liver fibrosis in patients with chronic hepatitis B.

BACKGROUND & AIMS: Precise assessment of liver fibrosis is necessary in patients with chronic liver disease. We investigated the performance of red cell volume distribution width-to-platelet ratio for the assessment of liver fibrosis in patients with chronic hepatitis B. METHODS: A total of 482 consecutive patients with chronic hepatitis B who underwent liver biopsy between October 2005 and May 2014 were recruited. Liver stiffness was measured using transient elastography. FIB-4 score, red cell volume distribution width-to-platelet ratio and the aspartate aminotransferase-to-platelet ratio index were also assessed. RESULTS: A total of 271 (56.2%) patients were males. The median age was 44 years. F1, F2, F3 and F4 fibrosis stages were identified in 68 (14.1%), 137 (28.4%), 64 (13.3%) and 213 (44.2%) of the patients respectively. The mean red cell volume distribution width-to-platelet ratio increased with liver fibrosis severity: F1, 0.065; F2, 0.077; F3, 0.097 and F4, 0.121 (P < 0.01). The area under the receiver operating characteristic curve of the red cell volume distribution width-to-platelet ratio for predicting significant fibrosis (≥F2) was 0.747. This result was inferior to transient elastography (0.866, P = 0.004), but comparable to FIB-4 (0.782, P = 0.427) and aspartate aminotransferase-to-platelet ratio index (0.716, P = 0.507). The area under the receiver operating characteristic curve of red cell volume distribution width-to-platelet ratio for predicting cirrhosis (F4) was 0.811, which was inferior to liver stiffness (0.915, P < 0.001), but comparable to FIB-4 (0.804, P = 0.805) and superior to aspartate aminotransferase-to-platelet ratio index (0.680, P < 0.001). CONCLUSIONS: The accuracy of red cell volume distribution width-to-platelet ratio was acceptable for the assessment of liver fibrosis in patients with chronic hepatitis B. When transient elastography is not available, red cell volume distribution width-to-platelet ratio assessment is a simple method that can be used to reduce the need for liver biopsy.

Disease duration and Medsger's severity score are associated with significant liver fibrosis in patients with systemic sclerosis.

OBJECTIVES: We investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidences of liver diseases due to viral infection, drug, and heavy alcohol consumption. METHODS: A total of 44 SSc patients were recruited. In addition to the clinical and laboratory data, the 2013 College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria score, modified Rodnan skin score (mRSS), and Medsger's severity score (MSS) were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis. RESULTS: The median age of patients (38 women) was 54 years and the median disease duration was 41.0 months. The median LS value was 4.6 kPa. The median mRSS and MSS were 7.0 and 5.0, respectively. Six (13.6%) patients had significant liver fibrosis. Disease duration (standardised ß=0.375, p=0.018) and MSS (standardised ß=0.398, p=0.047) significantly correlated with LS values. In multivariate analysis, disease duration≥63 months (odds ratio (OR) 19.166, 95% confidence interval 1.090, 336.962, p=0.043) and MSS≥7 (OR 19.796, 95% confidence interval 1.439, 272.252, p=0.026) independently predicted the presence of significant liver fibrosis. CONCLUSIONS: The prevalence of significant liver fibrosis was relatively high (13.6%) and its independent predictors were disease duration and MSS.

Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma: considerations for tumor response assessment.

Radiological response assessment criteria in hepatocellular carcinoma (HCC) have evolved to accurately evaluate tumor responses. The WHO criteria and the subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change in tumor size; however, these criteria generally ignore tumor necrosis and therefore may underestimate treatment responses. Thus, a panel of experts of the European Association for the Study of Liver (EASL) amended the response criteria to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was developed, which consider both the concept of tumor viability based on arterial enhancement and single linear summation, ultimately simplifying EASL criteria. Currently, the mRECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment. Here, the authors review application and performance of mRECIST as well as other HCC response assessment criteria and discuss unmet and open issues regarding response evaluation for HCC treatments.

Risk assessment of clinical outcomes in Asian patients with chronic hepatitis B using enhanced liver fibrosis test.

UNLABELLED: Serum fibrosis markers, such as the enhanced liver fibrosis (ELF) test, have been suggested as alternatives for liver biopsy (LB) in assessing liver fibrosis. We investigated the efficacy of the ELF test in predicting development of liver-related events (LREs) in patients with chronic hepatitis B (CHB). A total of 170 patients (103 men; 60.6%) with CHB who underwent LB and serological tests for determining ELFs were enrolled. All patients were followed up to monitor LRE development, defined as hepatic decompensation, hepatocellular carcinoma, and/or liver-related death. The mean age was 45.3 years. During the follow-up period (median, 41 months), 39 (22.9%) patients experienced LREs. In patients with LREs, age, proportion of male gender, ELF test results, age-spleen-platelet ratio (ASPRI), liver stiffness (LS) value, and proportion of histological cirrhosis were significantly higher than those in patients without LREs (all P < 0.05). Areas under the receiver operating characteristic curves to predict LRE development were 0.808 for the ELF test, 0.732 for LS value, 0.713 for histological fibrosis stages using Batts and Ludwig's scoring system, and 0.687 for ASPRI. On multivariate analysis, along with age, the ELF test was an independent predictor of LRE development (adjusted hazard ratio [HR], 1.438; P < 0.001). When we applied a three-tier stratification of our study population using cut-off ELF values of 8.10 and 10.40, patients with low (P = 0.002; adjusted HR: 0.045; 95% confidence interval [CI]: 0.006-0.330) and intermediate (P < 0.001; adjusted HR: 0.239; 95% CI: 0.122-0.469) ELF range were found less likely to develop LREs, compared to those with high ELF range. CONCLUSION: ELF is useful in a noninvasive prediction of LRE development. Transient elastography showed a statistically similar prognostic performance for LREs as the ELF, but other noninvasive tests were inferior.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

GOALS: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.