Validation of Diagnostic Thresholds for Compensated Advanced Chronic Liver Disease Using Supersonic Shear Imaging.

Background The Society of Radiologists in Ultrasound (SRU) has proposed thresholds for acoustic radiation force impulse techniques to diagnose compensated advanced chronic liver disease (cACLD). However, the diagnostic performance of these thresholds has not been extensively validated. Purpose To validate the SRU thresholds in patients with chronic liver disease who underwent supersonic shear imaging and, if suboptimal diagnostic performance is observed, to identify optimal values for diagnosing cACLD. Materials and Methods This retrospective single-center study included high-risk patients with chronic liver disease who had liver stiffness (LS) measurements and had undergone endoscopy or liver biopsy between January 2018 and December 2021. Patients were randomly allocated to test and validation sets. cACLD was defined as varices at endoscopy and/or severe fibrosis or cirrhosis at liver biopsy. The diagnostic performance of the SRU guidelines was evaluated, and optimal threshold values were identified using receiver operating characteristic (ROC) curve analysis. Results A total of 1180 patients (median age, 57 years [IQR, 50-64 years]; 761 men), of whom 544 (46%) had cACLD, were included. With the SRU recommended thresholds of less than 9 kPa and greater than 13 kPa in the test set (n = 786), the sensitivity and specificity for ruling out and ruling in cACLD were 81% (303 of 374 patients; 95% CI: 77, 85) and 92% (380 of 412 patients; 95% CI: 89, 94), respectively. In ROC curve analysis, the identified optimal threshold values were less than 7 kPa and greater than 12 kPa, showing 91% sensitivity (340 of 374 patients; 95% CI: 88, 93) for ruling out cACLD and 91% specificity (373 of 412 patients; 95% CI: 87, 93) for ruling in cACLD, respectively. In the validation set (n = 394), the optimal thresholds showed 91% sensitivity (155 of 170 patients; 95% CI: 86, 95) and 92% specificity (206 of 224 patients; 95% CI: 88, 95). Conclusion Compared with the SRU guidelines, the dual LS threshold values of less than 7 kPa and greater than 12 kPa were better for diagnosing cACLD. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Barr in this issue.

Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk. METHODS: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development. RESULTS: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up. CONCLUSIONS: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir. LAY SUMMARY: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC. METHODS: The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort. RESULTS: A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67). CONCLUSIONS: This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.

Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients.

BACKGROUND AND AIM: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. METHODS: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. RESULTS: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). CONCLUSIONS: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.

Application of Supersonic Shear Imaging to the Baveno VI Criteria and a Combination Model with Spleen Stiffness Measurement to Rule Out High-Risk Varices in Compensated Advanced Chronic Liver Disease.

PURPOSE: Recently, Colecchia et al. reported that by adding a spleen stiffness (SS) criterion sequentially to the Baveno VI criteria, screening endoscopy could be safely avoided. We aimed to compare the Baveno VI criteria, SS values and a sequential combination of the Baveno VI and SS values, measured by supersonic shear imaging (SSI), as approaches for safely avoiding screening endoscopy for high-risk varices (HRV). MATERIALS AND METHODS: Between April 2017 and July 2018, we enrolled 274 compensated advanced chronic liver disease patients who had successfully undergone liver stiffness (LS) and SS measurements with SSI and esophagogastroduodenoscopy (EGD). 52 HRV patients were included, and we analyzed risk factors for HRV and compared proportions of patients who were spared EGD when Baveno VI criteria, SS cut-off and the combination of the two approaches were used. RESULTS: The AUROC values for estimating HRV by platelet count, LS and SS were 0.701, 0.757 and 0.844, respectively, and all three measures were found to be independent predictors of HRV. The SS cut-off value for excluding HRV was ≤ 27.3 kPa. The percentages of patients spared EGD were 18.6 % for Baveno VI, 28.8 % for SS cut-off and 36.1 % for the sequential combination of Baveno VI and SS cut-off. Less than 2 % of HRV patients were missed when using all of the criteria. CONCLUSION: The Baveno VI criteria can be applied to LS measurement by SSI. SS measurement by SSI is an excellent predictor of HRV. Screening endoscopy can be safely avoided when Baveno VI criteria and SS cut-off are applied together.

Computed Tomography-Determined Body Composition Abnormalities Usefully Predict Long-term Mortality in Patients With Liver Cirrhosis.

OBJECTIVE: We evaluated the prognostic impacts of body composition components measured by computed tomography (CT) in patients with liver cirrhosis. METHODS: A total of 160 cirrhotic patients who underwent CT and hepatic venous pressure gradient measurements were retrospectively enrolled. Cross-sectional areas of skeletal muscle, visceral and subcutaneous fat, and mean CT attenuation of trabecular bone of the fourth lumbar vertebral level (L4HU) were measured. RESULTS: Multivariate analysis showed model for end-stage liver disease score [hazard ratio (HR), 1.086; 95% confidence interval (CI), 1.020-1.156; P = 0.010], hepatic venous pressure gradient (HR, 1.076; 95% CI, 1.021-1.135; P = 0.006), sarcopenia (HR, 1.890; 95% CI, 1.032-3.462; P = 0.039), and L4HU (HR, 1.960 for L4HU <145 Hounsfield units; 95% CI, 1.094-3.512; P = 0.024) were independently associated with long-term mortality. In patients with decompensated cirrhosis, subcutaneous adipose tissue index was the only independent predictor (HR, 0.984; 95% CI, 0.969-0.999; P = 0.039). CONCLUSION: Body composition abnormalities determined by CT are associated with long-term prognosis in cirrhotic patients.

No Difference in Incidence of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection Treated With Entecavir vs Tenofovir.

BACKGROUND & AIMS: Studies to evaluate risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with the nucelos(t)ide analogues entecavir or tenofovir have produced contradictory results. These differences are likely to be the result of censored data, insufficient observation periods, and different observation periods for patients treated with different drugs. We aimed to compare the incidence of HCC development between patients treated with oral entecavir or tenofovir and followed up for the same time periods. METHODS: We performed a retrospective study, collecting data from 1560 treatment-naive patients with chronic HBV infection who were first treated with entecavir (n = 753) or tenofovir (n = 807) from 2011 through 2015 at 9 academic hospitals in Korea. Clinical outcomes were recorded over a mean time period of 4.7 ± 1.0 years, from 92.4% of patients treated with tenofovir and 92.7% of patients treated with entecavir. RESULTS: Thirty-four patients in the entecavir group (4.5%) and 45 patients in the tenofovir group (5.6%) developed HCC during the follow-up period. The incidence of HCC did not differ significantly between groups, even in a 516-pair propensity score-matched population. CONCLUSIONS: In a retrospective study of 1560 treatment-naive patients with chronic HBV infection, the incidence of HCC did not differ significantly between patients treated with entecavir vs tenofovir over the same observation period. CLINICAL TRIAL: KCT0003487.

Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial.

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.

A Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A-Related Acute Liver Failure.

Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.

Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection.

BACKGROUND & AIMS: Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. METHODS: We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks. RESULTS: After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. CONCLUSIONS: BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.

Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.

GOALS: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). BACKGROUND: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. STUDY: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. RESULTS: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. CONCLUSIONS: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Spleen Stiffness Measurement Using 2-Dimensional Shear Wave Elastography: The Predictors of Measurability and the Normal Spleen Stiffness Value.

OBJECTIVES: To investigate the success rate of spleen stiffness measurement and factors that affect measurement success and to determine the spleen stiffness value of normal individuals by 2-dimensional shear wave elastography. METHODS: The spleen and liver stiffnesses of 313 consecutive patients were measured with SWE. The body mass index, abdominal wall thickness, spleen size, and liver stiffness of the patients were evaluated to identify factors associated with successful measurement of spleen stiffness. Patients were grouped by body mass index, spleen size, and liver stiffness, and the success rates and mean spleen stiffness values of the groups were compared. Independent predictors for successful spleen stiffness measurement and their cutoff values were evaluated. The mean spleen stiffness values of patients considered to have normal spleen stiffness were investigated. RESULTS: The overall success rate of spleen stiffness measurement was 52.9%. It was significantly higher in nonobese than in obese patients and in patients with splenomegaly and liver cirrhosis. The spleen stiffness value was higher in the splenomegaly group than the nonsplenomegaly group (P < .001) and increased as liver stiffness increased (P < .001). There was no significant difference in spleen stiffness values between the obese and nonobese groups. Abdominal wall thickness and splenic longitudinal diameter were identified as independent predictors of successful spleen stiffness measurement, and their cutoff values were 17.2 mm or less and greater than 9.4 cm, respectively. The mean spleen stiffness value ± SD of the normal patient group was 20.5 ± 5.4 kPa. CONCLUSIONS: The success rate of spleen stiffness measurement is lower than that of liver stiffness measurement. Spleen stiffness measurement is affected by abdominal wall thickness and spleen size.

The New Cutoff Value of the Hepatic Venous Pressure Gradient on Predicting Long-Term Survival in Cirrhotic Patients.

BACKGROUND: This study aimed to determine the prognostic role of the categorized hemodynamic stage (HS) based on the hepatic venous pressure gradient (HVPG) in patients with portal hypertension. METHODS: Of 1,025 cirrhotic patients who underwent HVPG measurement, data on 572 non-critically-ill patients were collected retrospectively between 2008 and 2013. The following two HS categorizations were used: HS-1 (6-9, 10-12, 13-16, 17-20, and > 20 mmHg; designated as groups 1-5, respectively) and HS-2 (6-12, 13-20, and > 20 mmHg). Clinical characteristics, mortality rates, and prognostic predictors were analyzed according to the categorized HS. RESULTS: During the mean follow-up period of 25 months, 86 (15.0%) patients died. The numbers of deaths in HS-1 groups were 7 (6.3%), 7 (6.9%), 30 (18.0%), 20 (15.6%), and 22 (34.4%), respectively (P < 0.001). However, the traditional HVPG cutoffs of 10 and 16 mmHg did not improve the discrimination of mortality. In contrast, the mortality rates did differ significantly between the three HS-2 groups (P < 0.05). In the multivariate analysis, all models revealed that HS-2 was a common prognostic factor in predicting mortality. The mortality rates increased significantly according to HS-2 in patients with hypoalbuminemia (HVPG, 13-20 mmHg; hazard ratio [HR], 2.54 and HVPG > 20 mmHg; HR, 5.45) and intermediate model for end-stage liver disease (MELD) score (HVPG, 13-20 mmHg; HR, 3.86 and HVPG > 20 mmHg; HR, 8.77; P < 0.05). CONCLUSION: Categorizing HVPG values according to HS-2 is a useful prognostic modality in patients with portal hypertension and can play an independent role in predicting the prognosis in patients with hypoalbuminemia and an intermediate MELD score.

Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis.

BACKGROUND & AIMS: Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6 mo) and long-term (6-120 mo) survival of patients with decompensated cirrhosis. METHODS: We performed a 10-year observation analysis using data from the Epidemiology and Natural History of Liver Cirrhosis study of patients with decompensated liver cirrhosis in Korea. Of the entire cohort (1595 patients enrolled at onset of decompensation since 2005), our analysis comprised 295 patients who immediately began treatment with entecavir (n = 179) or lamivudine (n = 116) after decompensation. We collected laboratory test results, data on hepatocellular carcinoma (HCC) development, and Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores. The mean follow-up time was 62.3 ± 36.5 months. The primary end point was time of liver transplant-free survival. RESULTS: The median survival time was 7.7 years; 60.1% of patients survived for 5 years and 45.7% survived for 10 years without liver transplantation. An MVR was observed in 116 patients (39.3%); these patients had significantly longer times of transplant-free survival than patients without MVR. Survival times associated with the occurrence of HCC; survival of patients without HCC was excellent if they survived the first 6 months after initiation of antiviral therapy, whereas the survival rates of patients with HCC decreased persistently over time. A baseline MELD score above 20 and multiple complications were associated with short-term mortality. MVR was the factor most strongly associated with long-term transplant-free survival. Significantly higher proportions of patients who received entecavir survived 10 years compared with patients who received lamivudine, but no difference was observed among patients with MVRs. Patients with MVRs had significant improvement in hepatic function over time, but nonsignificant reductions in risk of HCC or HCC-related mortality. CONCLUSIONS: In a 10-year observation study of patients in Korea with HBV-related decompensated cirrhosis, we found baseline MELD score and MVR to entecavir or lamivudine to associate with short- and long-term transplant-free survival. The benefits of an MVR are maintained for up to 10 years even after decompensation, but patients are still at risk for HCC.

Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure.

BACKGROUND AND AIM: The aim of this study was to validate the chronic liver failure-sequential organ failure assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score in Korean chronic liver disease patients with acute deterioration. METHODS: Acute-on-chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristic curve. RESULTS: Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, model for end-stage liver disease, and model for end-stage liver disease-Na scores in ACLF patients according to the CLIF-C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. CONCLUSIONS: The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition.

Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites.

BACKGROUND AND AIM: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. METHODS: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1). RESULTS: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis. CONCLUSION: Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites.

Coefficient of Variance as Quality Criterion for Evaluation of Advanced Hepatic Fibrosis Using 2D Shear-Wave Elastography.

OBJECTIVES: To compare the diagnostic performance for advanced hepatic fibrosis measured by 2D shear-wave elastography (SWE), using either the coefficient of variance (CV) or the interquartile range divided by the median value (IQR/M) as quality criteria. METHODS: In this retrospective study, from January 2011 to December 2013, 96 patients, who underwent both liver stiffness measurement by 2D SWE and liver biopsy for hepatic fibrosis grading, were enrolled. The diagnostic performances of the CV and the IQR/M were analyzed using receiver operating characteristic curves with areas under the curves (AUCs) and were compared by Fisher's Z test, based on matching the cutoff points in an interactive dot diagram. All P values less than 0.05 were considered significant. RESULTS: When using the cutoff value IQR/M of 0.21, the matched cutoff point of CV was 20%. When a cutoff value of CV of 20% was used, the diagnostic performance for advanced hepatic fibrosis ( ≥ F3 grade) with CV of less than 20% was better than that in the group with CV greater than or equal to 20% (AUC 0.967 versus 0.786, z statistic = 2.23, P = .025), whereas when the matched cutoff value IQR/M of 0.21 showed no difference (AUC 0.918 versus 0.927, z statistic = -0.178, P = .859). CONCLUSIONS: The validity of liver stiffness measurements made by 2D SWE for assessing advanced hepatic fibrosis may be judged using CVs, and when the CV is less than 20% it can be considered "more reliable" than using IQR/M of less than 0.21.