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Background: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis. We investigated the associations between changes in liver stiffness measurement (LSM) over 3-year period and the development of cirrhosis or hepatocellular carcinoma (HCC) in patients with MASLD., Methods: This study involved patients with MASLD who underwent transient elastography at baseline and 3 years after baseline from 2012 to 2020. Low (L), indeterminate (I) and high (H) LSM values were classified as <8 kPa, 8-12 kPa and >12 kPa respectively., Results: Among 1738 patients, 150 (8.6%) were diagnosed with cirrhosis or HCC. The proportions of patients with L, I and H risk were 69.7%, 19.9% and 10.5% at baseline, and 78.8%, 12.8% and 8.4% at 3 years after baseline, respectively. The incidence rates of cirrhosis or HCC per 1000 person-years were 3.7 (95% confidence interval [CI], 2.4-5.5) in the L → L + I group, 23.9 (95% CI, 17.1-32.6) in the I → L + I group, 38.3 (95% CI, 22.3-61.3) in the H → L + I group, 62.5 (95% CI, 32.3-109.2) in the I → H group, 67.8 (95% CI, 18.5-173.6) in the L → H group and 93.9 (95% CI 70.1-123.1) in the H → H group. Two risk factors for the development of cirrhosis or HCC were LSM changes and low platelet counts., Conclusion: LSM changes could predict clinical outcomes in patients with MASLD. Thus, it is important to monitor changes in the fibrotic burden by regular assessment of LSM values., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aims: : Reports on the association between sarcopenic visceral obesity and non-alcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities., Methods: : The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (<0.789 for men and <0.512 for women)., Results: : In total, 82.0% (n=1,205) of the entire study population had NAFLD, and 14.6% of these individuals (n=176) exhibited significant liver fibrosis. Individuals with the lowest SV ratio had a significantly increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk (all p<0.05). Individuals with both the lowest SV ratio and sarcopenia had the highest risk of developing NAFLD (odds ratio [OR]=3.11), significant liver fibrosis (OR=2.03), and high ASCVD risk (OR=4.15), compared with those with a higher SV ratio and without sarcopenia (all p<0.05)., Conclusions: : Low SV ratio combined with sarcopenia was significantly associated with an increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk among individuals with a high risk of NAFLD.

Introduction: The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history., Methods: From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels <2,000 IU/mL; LLV was defined as having at least 1 detectable serum HBV-DNA (20-2,000 IU/mL) episode, whereas maintained virological response (MVR) was defined as having persistently undetectable serum HBV-DNA (<20 IU/mL). When serum HBV-DNA was ≥2,000 IU/mL during follow-up, AVT was administered according to guidelines. Study end points were development of cirrhotic complication event (CCE) or hepatocellular carcinoma (HCC)., Results: Among 567 patients analyzed, cumulative HCC risk at 3, 5, and 7 years was comparable between LLV (n = 391) vs MVR (n = 176) groups (5.7%, 10.7%, and 17.3% vs 7.2%, 15.5%, and 19.4%, respectively [P = 0.390]). CCE risk was also comparable between 2 groups (7.5%, 12.8%, and 13.7% vs 7.8%, 12.3%, and 14.6%, respectively [P = 0.880]). By multivariate analysis, LLV (vs MVR) was not associated with HCC or CCE risks, with adjusted hazard ratios of 1.422 (95% confidence interval [CI] 0.694-2.913; P = 0.336) and 1.816 (95% CI: 0.843-3.911; P = 0.128), respectively. Inverse probability of treatment weighting analysis yielded comparable outcomes between 2 groups, regarding HCC and CCE risks with hazard ratios of 0.903 (95% CI: 0.528-1.546; P = 0.711) and 1.192 (95% CI: 0.675-2.105; P = 0.545), respectively., Discussion: Episodic LLV among untreated patients with compensated cirrhosis does not increase the risk of disease progression compared with MVR status. Thus, the benefits of AVT for episodic LLV should be re-evaluated., (Copyright © 2021 by The American College of Gastroenterology.)

Background and Aim: Cardiovascular disease (CVD) is the principal cause of death in patients with type 2 diabetes (T2D). In this study, we assessed whether liver fibrosis predicted the risk of CVD in patients with T2D., Methods: A total of 1481 patients who had commenced oral antidiabetic drugs to treat newly diagnosed T2D between 2006 and 2010 were recruited. The fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), and BARD score were used to assess fibrotic burden at the time of T2D diagnosis., Results: During the follow-up period (median 88.1 [interquartile range 36.6-113.6] months), 242 (16.3%) patients developed CVD. CVD occurred frequently in older patients and was associated with hypertension; metabolic syndrome; obesity; smoking; administration of statin, which is an antihyperlipidemic drug; lower platelet counts; lower alanine aminotransferase, total cholesterol, and HbA1c levels; higher C-peptide and homeostatic model assessment of insulin resistance levels; and higher FIB-4, NFS, and BARD score (all P < 0.05). FIB-4 (hazard ratio [HR] = 1.163), NFS (HR = 1.322), BARD score (HR = 1.564), metabolic syndrome (HR = 1.556), smoking (HR = 2.829), and statin use (HR = 0.603) independently predicted the risk of CVD (all P < 0.05). The cumulative incidence of CVD was significantly different among groups stratified by liver fibrotic burden (all P < 0.05, log-rank test). Competing risk analysis showed a significant association between the severity of liver fibrosis and CVD development (all P < 0.001, Gray's test)., Conclusions: The severity of liver fibrosis independently predicted CVD in patients with T2D. Thus, assessment of liver fibrosis might allow physicians to optimize the timing of appropriate cardiovascular interventions in such patients., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea., Methods: A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%])., Results: Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality ( P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test)., Conclusion: The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background/aims: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) share pathophysiological mechanism. Metformin is a widely used first-line anti-diabetic drug. We investigated the evolution of liver fibrosis and steatosis during 2-year use of metformin in patients with T2DM., Methods: Between 2006 and August 2010, patients newly diagnosed with T2DM who received metformin as the first-line treatment were recruited. Fibrosis-4 index (FIB-4) > 2.67 and hepatic steatosis index (HSI) > 36.0 was used to define advanced liver fibrosis and fatty liver, respectively., Results: A total of 1292 (mean age 60.8 years, 57% men and 43% women) patients were recruited. The mean FIB-4 and HSI scores were 1.38 and 27.3, respectively. At enrollment, 83 (6.4%) patients had advanced liver fibrosis and 429 (33.2%) had fatty liver. After 2 years of metformin treatment, the mean FIB-4 score increased from 1.38 to 1.51 (p < 0.001), whereas the mean HSI score decreased from 27.3 to 26.5 (p < 0.001). During follow-up, advanced liver fibrosis additionally developed in 52/1209 (4.3%) patients, whereas 48/83 (57.8%) experienced fibrosis regression. Older age (odds ratio [OR] = 1.007), lower platelet count (OR = 0.993), and lower serum albumin (OR = 0.325) were independently associated with the increased risk of advanced liver fibrosis development after 2-years of metformin treatment., Conclusion: In our cohort of patients with metformin treatment, a small proportion of patients developed liver fibrosis and steatosis after 2 years. Optimized follow-up strategy is required according to different risk of liver fibrosis progression in patients with T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Long-term suppression of hepatitis B virus with tenofovir (TDF) induces fibrosis regression, and repeated liver stiffness (LS) measurement can indicate the improvement of fibrosis. We aimed to investigate predictors for LS improvement assessed by changes in patients receiving long-term TDF therapy in chronic hepatitis B (CHB) with liver cirrhosis. CHB patients with histologically proven liver cirrhosis who received TDF as the first-line therapy from 2012 to 2015 were recruited. LS and controlled attenuation parameter (CAP) measurements were repeated at baseline and 3 years after therapy. Liver stiffness improvement was defined as a drop of LS value ≥30% from the baseline. A total of 131 patients were enrolled (mean age 51.4% and male 64.9%). After 3 years of TDF therapy, the mean LS value significantly improved (from 14.7 to 8.6 kPa, P < .001), and 96 (73.3%) patients have achieved LS improvement. Predictors associated with improvement of LS were low body mass index (BMI), HBeAg positivity, and low CAP value at baseline. In multivariate analysis, low BMI was a single factor independently associated with LS improvement (odds ratio 0.680, 95% CI 0.560-0.825, P < .001). Patients with BMI < 23.5, had a 1.96 times more chance of achieving LS improvement compared to those with BMI ≥ 23.5 (90.1% vs. 46.0%, P = .001). High BMI was a single significant factor hindering the fibrosis improvement in patients receiving long-term TDF therapy in CHB with liver cirrhosis. Life style modification and BMI reduction should be encouraged to enhance fibrosis improvement., (© 2020 John Wiley & Sons Ltd.)

Background and Aims: Sarcopenia is associated with fibrotic burden in patients with chronic hepatitis B. We investigated the dynamic association between fibrosis changes and appendicular skeletal muscle mass during antiviral therapy in patients with chronic hepatitis B., Methods: Between 2015 and 2018, chronic hepatitis B patients who received paired transient elastography to assess fibrotic burden in the liver and bioelectrical impedance analysis to assess appendicular skeletal muscle mass were recruited retrospectively. The sarcopenia index was calculated as total appendicular skeletal muscle mass/body mass index. Significant liver fibrosis was defined as a liver stiffness value≥8 kPa., Results: In total, 223 (53.7%) received antiviral therapy, whereas 192 (46.3%) did not. Appendicular skeletal muscle mass decreased significantly in the antiviral therapy group (mean 21.16→21.00 kg, P = 0.01), but not in the non-antiviral therapy group (mean 20.77→20.64 kg, P = 0.134). In a subgroup with significant liver fibrosis, similar findings were observed (mean 20.73→20.54 kg in antiviral therapy group, P = 0.037; mean 21.39→21.07 kg in the non-antiviral therapy group, P = 0.097). Older age, male gender, higher body mass index, and higher aspartate aminotransferase were significantly associated with the increased risk of appendicular skeletal muscle mass reduction (≥5% from the baseline)., Conclusions: Appendicular skeletal muscle mass significantly decreased during antiviral therapy in patients with chronic hepatitis B patients., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis., Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19., Results: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients., Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Introduction: There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA)., Objective: We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA., Methods: This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used., Results: There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40-6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59-12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05-3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037)., Conclusions: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA., (© 2020 S. Karger AG, Basel.)

Objectives: Comorbidities and conventional risk factors influence the prognosis of patients with rheumatoid arthritis (RA). We investigated whether liver fibrosis burden is associated with all-cause mortality in patients with RA. Methods: A total of 2812 patients with RA were retrospectively selected and reviewed. Liver fibrosis was assessed using the fibrosis-4 index (FIB-4) [age (years)× aspartate aminotransferase level (IU/L)/platelet count (10 9 /L)/√alanine aminotransferase (IU/L)]. Results: The mean patient age was 51.5 years (482 men and 2330 women). The mean erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and FIB-4 were 43.5 mm/h, 9.0 mg/L, and 1.0, respectively. Methotrexate was used in 2524 (89.9%) patients, and biological or targeted synthetic disease-modifying antirheumatic drugs were used in 310 (11.0%) patients. During the follow-up period (mean 93.7 months), 89 (3.2%) patients died. Deceased patients had a significantly higher age (mean 64.4 vs. 51.1 years); frequency of male sex (31.5% vs. 16.7%), hypertension (HTN; 40.4 vs. 18.5%), and diabetes mellitus (DM; 25.8% vs. 7.7%); ESR (mean 57.1 vs. 43.0 mm/h); CRP (mean 16.9 vs. 8.7 mg/L); and FIB-4 (mean 1.5 vs. 1.0) (all p  < .05) than the survivors. On multivariate analysis, higher FIB-4 was found to be independently associated with a higher rate of all-cause mortality (hazard ratio =1.130, p  = .004), together with male sex, HTN, DM, ESR, and intensity of glucocorticoid exposure, whereas the use of methotrexate was independently protective (all p  < .05). Conclusion: Besides conventional risk factors, fibrotic burden, assessed using FIB-4, might be useful for risk stratification of patients newly diagnosed as having RA.

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). We investigated whether P-I-R (progressive vs. indeterminate vs. regressive) staging is predictive of hepatocellular carcinoma (HCC) recurrence in patients with chronic hepatitis B (CHB) taking AVT who underwent resection. Patients with CHB-related HCC who underwent curative resection between 2004 and 2017 and had received ≥2 years AVT at the time of resection were eligible. Two pathologists performed P-I-R staging. In total, 104 patients with CHB-related HCC were enrolled. The mean age of the study population was 56.3 years. The mean duration of AVT at the time of resection was 62.6 months. During the follow-up period (mean, 45.5 months), 20 (19.2%) and 14 (13.5%) patients developed early and late recurrence of HCC, respectively. The cumulative incidence of late recurrence was significantly lower in patients with regressive patterns than in those with indeterminate and progressive patterns according to P-I-R staging (P = 0.015, log-rank test), although the cumulative incidence of overall recurrence according to P-I-R staging was similar. Hepatitis B virus DNA levels (hazard ratio [HR] = 3.200, P = 0.020) and the regressive P-I-R staging pattern (HR = 0.127, P = 0.047) independently predicted the risk of late recurrence. One-time assessment of the P-I-R staging at the time of curative resection in patients with CHB-related HCC receiving AVT independently predicted late HCC recurrence. Therefore, qualitative fibrosis assessment by P-I-R staging might be useful in predicting the outcomes of patients with CHB undergoing AVT.

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.

Background and Aims: The modified PAGE-B (mPAGE-B) score comprising age, gender, platelet count and albumin was recently proposed to predict hepatocellular carcinoma (HCC) risk among chronic hepatitis B (CHB) patients undergoing antivirals. Here, in the independent cohort, we externally validated the predictive performance of the mPAGE-B score and compared it with those of conventional HCC prediction models., Methods: We consecutively recruited CHB patients treated with lamivudine, entecavir or tenofovir as the first-line antiviral regimen. Patients with decompensated cirrhosis or HCC at baseline were excluded. Predictive performances of the mPAGE-B score and other models were assessed with comparison., Results: Among 1330 patients, 9.6% developed HCC during follow-up. The mPAGE-B score provided the highest Harrell's c-index (0.769), followed by the GAG-HCC (0.751), PAGE (0.744), REACH-B (0.686) and CU-HCC (0.618) scores. The mPAGE-B score showed the similar performance to the PAGE-B and GAG-HCC scores and the better performance than the REACH-B and CU-HCC scores. Cumulative HCC probabilities at 5- and 7-years were 0.0% and 0.0% in low-risk group (mPAGE-B score ≤ 8), 6.1% and 10.8% in intermediate-risk group (mPAGE-B score 9-12) and 18.7% and 26.7% in high-risk group (mPAGE-B score ≥ 13) respectively (both P < 0.001 between adjacent two groups). C-indices of the mPAGE-B score were 0.785 and 0.724 among subgroups treated with entecavir or tenofovir (n = 1011) and with lamivudine (n = 319), respectively, which are overall similar to those of the PAGE-B score., Conclusion: The mPAGE-B score showed acceptable predictive performances. Compared to the PAGE-B score, addition of albumin as a constituent provided the marginal benefit., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Serum hepatitis B virus (HBV)-DNA > 2,000 IU/mL is associated with higher risk of disease progression. However, without hepatocellular carcinoma (HCC) or cirrhosis, nucleos(t)ide analogs (NUCs) are recommended only for patients with elevated serum HBV-DNA and alanine aminotransferase ≥2 × upper normal limit., Methods: We evaluated prognosis of untreated minimally active (MA) hepatitis patients (defined as HBV-DNA > 2,000 IU/mL, but never fulfilling current criteria for NUCs during follow-up) (untreated MA group), compared to virological responders by NUCs (NUC-VR group). Eligible patients undergoing transient elastography were consecutively enrolled. Patients with an immune-tolerant or inactive phase and with cirrhosis or HCC at enrollment were excluded. Cumulative risks of disease progression were assessed using the Kaplan-Meier method., Results: The untreated MA group (n = 152) had higher HBV-DNA, alanine aminotransferase, and total bilirubin levels, and lower proportions of male and positive hepatitis B e antigen, compared to the NUC-VR group (n = 641). The untreated MA group had higher risks of HCC (adjusted hazard ratio [HR] 3.485, 95% confidence interval [CI] 1.234-9.846; P = 0.018), but similar risks of cirrhotic complications (adjusted HR 0.649, 95% CI 0.227-1.854; P = 0.420), compared to the NUC-VR group. Inverse probability of treatment weighting analysis using propensity score showed that the untreated MA group had higher risks of HCC (HR 4.464, 95% CI 2.008-9.901; P < 0.001), but similar risks of cirrhotic complications (HR 1.171, 95% CI 0.594-2.309; P = 0.649), compared to the NUC-VR group., Discussion: Through appropriate adjustment of potential prognostic factors, the untreated MA group consistently showed higher risks of HCC, but similar risks of cirrhotic complications, compared to the NUC-VR group. HCC risk might be reduced through earlier NUCs for the untreated MA group.

Background/aims: Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status., Methods: A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development., Results: The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p<0.05). Cirrhosis significantly predicted the risk of HCC development in subgroups with and without ongoing AVT at enrollment, regardless of adjustment., Conclusions: Our study showed that cirrhosis, not AVT and HBV-related variables, was associated with HCC development in a cohort of patients with heterogeneous HBV status. Our results may help clinicians apply individualized surveillance strategies according to fibrotic status in patients with CHB.

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, 145×10 9 /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.

Objectives: We evaluated the laboratory and radiological data on liver and investigate liver fibrosis induced by hepatic manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) using the aspartate aminotransferase to platelet ratio index (APRI) and an index of fibrosis (FIB-4) in 136 immunosuppressive drug-naïve patients., Methods: We retrospectively reviewed the medical records of 136 patients with AAV without chronic liver diseases or autoimmune diseases. We collected the laboratory and imaging results. We assessed liver fibrosis by APRI and FIB-4. The critical cut-offs of APRI and FIB-4 for predicting liver fibrosis are 0.5 and 1.45. The optimal cut-off of five factor score (FFS) at diagnosis for FIB-4 ≥1.45 was extrapolated by the area under the receiver operator characteristic curve., Results: The mean age at diagnosis was 54.6 years and 32.4% of patients were male (69 MPA, 38 GPA and 29 EGPA). The percentage of patients having the normal results of liver function tests was ranging from 86.0% to 95.6%. There were no patients who exhibited the significantly abnormal findings on imaging studies. Nonetheless, twenty-nine patients with AAV (21.3%) exhibited subclinical but significant liver fibrosis at diagnosis based on FIB-4. Patients with FFS ≥1 had a significantly higher risk of having subclinical but significant liver fibrosis (FIB-4 ≥1.45) than those with FFS <1 (RR 12.486)., Conclusions: AAV may increase the results of liver function tests and it may provoke subclinical but significant liver fibrosis at diagnosis. Furthermore, liver fibrosis should be considered in AAV patients having FFS ≥1.

Background & Aims: We compared the risk of hepatocellular carcinoma (HCC) development between patients with chronic hepatitis B (CHB) who achieved virological response (VR; HBV-DNA < 2000 IU/mL) with nucleos(t)ide analogues (NUCs) treatment (NUC-VR group) and patients with inactive CHB phase (ICHBP group)., Methods: To adjust for imbalances between NUC-VR and ICHBP groups, propensity score matching (PSM) models with 1:1 ratios were performed., Results: This study included 2032 patients (n = 1291 in NUC-VR group and n = 741 in ICHBP group). Before PSM, NUC-VR group was at higher risk of HCC development than ICHBP group at 7 years (9.4% in NUC-VR group vs 3.3% in ICHBP group; P < 0.001). However, after PSM, the cumulative HCC development rates at 7 years were similar in NUC-VR and ICHBP groups using the three PSM models [2.0% vs 4.3%, PSM model-1 (612 pairs); 3.7% vs 4.4%, PSM model-2 (618 pairs); and 2.4% vs 4.3%, PSM model-3 (610 pairs)] (all P > 0.05)., Conclusions: After adjusting heavier hepatic fibrosis burden in NUC-VR group, overall clinical outcomes between 2 groups had become comparable. Therefore, if appropriate, NUCs to prevent viral replication and hepatic inflammation are required for achieving better prognosis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To investigate whether there are differences in long-term all-cause and cardiovascular mortality according to the burden of liver fibrosis or steatosis in patients with ischaemic stroke or transient ischaemic attack (TIA). -Methods: Consecutive patients with acute ischaemic stroke or TIA who underwent transient elastography (TE) from January 2014 to December 2014 were considered eligible. The influence of liver fibrosis or steatosis, assessed via TE, on long-term outcomes was investigated using Cox proportional hazard models., Results: Among 395 patients included in this study, there were 37 (9%) patients with significant fibrosis (> 8.0 kPa) and 164 (41.5%) patients with fatty liver (> 250 dB/m). During the follow-up period (median 2.7 years), all-cause and cardiovascular mortality occurred in 28 (7.1%) and 20 (5.1%) patients. On multivariate analyses, significant liver fibrosis was independently associated with increased risk of all-cause (hazard ratio [HR] 8.14, 95% CI 3.03-21.90, p < 0.001) and cardiovascular (HR 4.29, 95% CI 1.10-16.73, p = 0.036) mortality, whereas fatty liver was not (all p > 0.05)., Conclusions: This study found that the burden of liver fibrosis but not that of steatosis, assessed via TE, was an independent predictor of all-cause and cardiovascular mortality during long-term follow-up in patients with ischaemic stroke., (© 2019 S. Karger AG, Basel.)

Background: Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B., Methods: Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass [kg]/body mass index [kg/m 2 ]) was calculated using dual-energy X-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut-offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis-4 index ≥2.67., Results: Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37-3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67-3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04-2.62 by the fibrosis-4 index; all P < 0.05)., Conclusions: Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis., (© 2018 John Wiley & Sons Ltd.)

Background: Interferon (IFN)-based regimens cause significant impairment of health-related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN-free regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV patients is unclear due to lack of published evidence., Aim: To assess HRQL in East Asian HCV patients treated with an IFN-free regimen with sofosbuvir+ribavirin., Methods: Patients completed Short Form-36 (SF-36) before, during and after treatment., Results: 686 subjects were included (China: 56.7%; S. Korea: 18.8%; Taiwan: 12.7%; genotype 2: 40.8%; genotype 1: 29.6%; genotype 3: 18.4%; genotype 6: 11.2%; cirrhosis: 13.4%; treatment-naïve: 66.5%). Patients received either pegylated-IFN, sofosbuvir, and ribavirin (IFN+SOF+RBV) for 12 weeks (n = 155, genotypes 1 and 6) or SOF+RBV for 12-24 weeks (n = 531, all genotypes). The SVR-12 rates were 95.5% and 96.0%; respectively (P = .76). Baseline HRQL scores were similar between treatment groups (all P > .05). By the end of treatment, the IFN-treated group experienced significant declines in most HRQL scores (on average, by up to -13.3 points on a 0-100 scale from the baseline level, P < .02) while subjects on SOF/RBV had milder impairments (up to -5.4 points). Achieving SVR-12 was associated with HRQL improvement regardless of regimen (up to +2.9 points, P < .05). The use of IFN-free treatment was a consistent independent predictor of higher HRQL scores during treatment (β: +2.1 to +10.7 points, P < .02)., Conclusions: East Asian HCV patients treated with an IFN-free regimen had better on-treatment HRQL scores. These data should inform policymakers about the comprehensive benefits of IFN-free regimens in East Asian patients with HCV., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Liver cirrhotic patients suffer from a seemingly unpredictable risk of hepatocellular carcinoma (HCC). Here, an HCC risk score R (0 ≦ R ≦ 1) was derived from commonly tested haematological and biochemical parameters. In the score-derivation Taiwanese cohort (144 cirrhosis versus 48 HCC-remission patients), the score had an area-under-the-curve (AUC) of 0.70 (95% confidence interval [CI], 0.61-0.78, P < 0.001). When validated in a Korean cohort (78 cirrhosis versus 23 HCC-remission patients), the AUC was 0.68 (CI, 0.56-0.80, P = 0.009). In a multicentre prospective cohort (478 cirrhotic patients prospectively followed for HCC occurrence), the hazard ratio with respect to R was 2.344 (CI = 1.183-4.646, P = 0.015). The cumulative incidences of HCC at two years after patient enrolment were 9.6% and 1.7% for the high-risk (R ≧ 0.5) and low-risk (R < 0.5) groups, respectively (P < 0.001). At the end of the study, the incidences were 10.9% and 5.0%, respectively (P = 0.012). The majority of HCCs (23/26) in the high-risk group emerged within the first two years of follow-up. In conclusion, an HCC risk score was developed for cirrhotic patients that effectively predicted HCC in a prospective cohort study.

Background & Aims: Several risk prediction models for hepatocellular carcinoma (HCC) development are available. We explored whether the use of risk prediction models can dynamically predict HCC development at different time points in chronic hepatitis B (CHB) patients., Methods: Between 2006 and 2014, 1397 CHB patients were recruited. All patients underwent serial transient elastography at intervals of >6 months., Results: The median age of this study population (931 males and 466 females) was 49.0 years. The median CU-HCC, REACH-B, LSM-HCC and mREACH-B score at enrolment were 4.0, 9.0, 10.0 and 8.0 respectively. During the follow-up period (median, 68.0 months), 87 (6.2%) patients developed HCC. All risk prediction models were successful in predicting HCC development at both the first liver stiffness (LS) measurement (hazard ratio [HR] = 1.067-1.467 in the subgroup without antiviral therapy [AVT] and 1.096-1.458 in the subgroup with AVT) and second LS measurement (HR = 1.125-1.448 in the subgroup without AVT and 1.087-1.249 in the subgroup with AVT). In contrast, neither the absolute nor percentage change in the scores from the risk prediction models predicted HCC development (all P > .05). The mREACH-B score performed similarly or significantly better than did the other scores (AUROCs at 5 years, 0.694-0.862 vs 0.537-0.875)., Conclusions: Dynamic prediction of HCC development at different time points was achieved using four risk prediction models, but not using the changes in the absolute and percentage values between two time points. The mREACH-B score was the most appropriate prediction model of HCC development among four prediction models., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aims: Liver stiffness (LS) was assessed using transient elastography, and the enhanced liver fibrosis (ELF) test was performed to accurately assess fibrotic burden. We validated the LS-ELF algorithm and investigated whether the sequential LS-ELF algorithm performs better than concurrent combination of these analyses in chronic hepatitis B (CHB) patients., Methods: Between 2009 and 2013, 222 CHB patients who underwent liver biopsy (LB), as well as LS measurement and the ELF test, were enrolled., Results: Advanced fibrosis (≥F3) and cirrhosis (F4) were identified in 141 (63.6%) and 118 (53.2%) patients, respectively. Areas under receiver operating characteristic curve for LS predictions of ≥F3 (0.887 vs 0.703) and F4 (0.853 vs 0.706) were significantly higher than the ELF test (all p＜0.001). Based on the LS-ELF algorithm, 60.4% to 71.6% and 55.7% to 66.3% of patients could have avoided LB to exclude ≥F3 and F4, respectively, whereas 68.0% to 78.7% and 63.5% to 66.1% of patients could have avoided LB to confirm ≥F3 and F4, respectively. When confirmation and exclusion strategies were applied simultaneously, 69.4% to 72.5% and 60.8% to 65.3% of patients could have avoided LB and been diagnosed as ≥F3 and F4, respectively. The proportion of patients who correctly avoided LB for the prediction of ≥F3 (69.4% to 72.5% vs 42.3% to 59.0%) and F4 (60.8% to 65.3% vs 23.9% to 49.5%) based on the sequential LS-ELF algorithm was significantly higher than the concurrent combination (all p＜0.05)., Conclusions: The sequential LS-ELF algorithm conferred a greater probability of avoiding LB in CHB patients to diagnose advanced fibrosis and cirrhosis, and this test performed significantly better than the concurrent combination.

Background and Aim: A subcirrhotic range of liver stiffness (sc-LS), assessed by transient elastography, is associated with better outcomes in patients with chronic hepatitis B (CHB). We investigated whether the achievement of sc-LS by antiviral therapy (AVT) reduced the risk of developing hepatocellular carcinoma (HCC) in patients with CHB-related advanced fibrosis or cirrhosis., Methods: In total, 209 patients with CHB-related advanced fibrosis or cirrhosis, who received paired transient elastography examinations during AVT between 2007 and 2012, were enrolled. The cut-off LS value for ultrasonographic cirrhosis was defined as 11.6 kPa., Results: The median age of the study population was 51 years, with males predominating (n = 138, 66.0%). The median LS value at enrollment was 14.1 kPa (interquartile range: 9.5-24.1 kPa). After 2 years of AVT, 140 (67.0%) patients achieved sc-LS. During the study period, 28 (13.4%) patients developed HCC after 2 years of AVT. On multivariate analysis, the achievement of sc-LS after AVT was independently associated with a decreased risk of HCC development (hazard ratio [HR] = 0.485, P = 0.047), whereas older age (HR = 1.071) and male gender (HR = 3.704) were independently associated with an increased HCC risk (both P < 0.05). Patients with a cirrhotic range of LS value after 2 years of AVT were at a higher risk of HCC development than those with sc-LS (log-rank test, P = 0.020)., Conclusions: The achievement of sc-LS after AVT can reduce the risk of HCC development in patients with CHB, even when advanced fibrosis or cirrhosis is apparent on starting AVT., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background/aims: The renal effects of nucleos(t)ide analogs in patients with chronic hepatitis B are controversial. We aimed to compare the impact of entecavir (ETV) and tenofovir (TDF) on renal function in patients with hepatitis B virus (HBV)-related cirrhosis., Methods: We performed a retrospective cohort study of 235 consecutive treatment-naïve patients with HBV-related cirrhosis who were treated with ETV or TDF between December 2012 and November 2013 at Severance Hospital, Seoul, Korea., Results: Compensated cirrhosis was noted in 183 patients (ETV 130, TDF 53), and decompensated cirrhosis was noted in 52 patients (ETV 32, TDF 20). There were no significant changes in estimated glomerular filtration rates (eGFR) from baseline in either the ETV- or TDF-treated groups at week 96 (Chronic Kidney Disease Epidemiology Collaboration, ETV -1.68% and TDF -5.03%, p=0.358). Using a multivariate analysis, the significant factors associated with a decrease in eGFR >20% were baseline eGFR, diabetes mellitus (DM), and the use of diuretics. The use of antiviral agents and baseline decompensation were not determined to be significant factors., Conclusions: In patients with HBV-related cirrhosis, TDF has shown similar renal safety to that of ETV over a 2-year period. Renal function should be closely monitored, especially in patients who exhibit decreasing eGFR, DM, and the use of diuretics.

Background/aims: Transient elastography (TE) can be used to assess the degree of liver fibrosis and steatosis. We investigated the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) with or without significant liver fibrosis in the general population., Methods: A total of 3033 subjects without alcoholic or chronic viral liver diseases who underwent a medical health check-up including TE were recruited from April 2013 to August 2014. TE-defined NAFLD was defined as a controlled attenuation parameter of ≥250 dB/m, and significant liver fibrosis was defined as a liver stiffness (LS) value of ≥8 kPa., Results: Overall, 1178 (42.9%) subjects had NAFLD. Subjects with NAFLD had significantly higher alanine aminotransferase (ALT) levels and a higher prevalence of parameters related to metabolic syndrome, such as high blood pressure, a high body mass index (BMI), glucose intolerance, and dyslipidemia than did subjects without NAFLD (all P < 0.05). Age, male gender, ALT level, serum albumin, BMI, diabetes, hypertriglyceridemia, and LS values independently showed positive associations with the presence of NAFLD (all P < 0.05). In addition, concomitant significant liver fibrosis was identified in 60 (5.1%) subjects with NAFLD, and its independent predictors were age [odds ratio (OR) 1.054], ALT level (OR 1.019), BMI (OR 1.217), and diabetes (OR 1.987) (all P < 0.05)., Conclusions: We found that the prevalence of subjects with NAFLD was high (42.9%), and 5.1% of them had concomitant significant liver fibrosis. The risk factors found in this study can help identify which subjects with NAFLD are vulnerable to fibrosis progression.

Although several human clinical trials using various bone marrow-derived cell types for cirrhotic or decompensated patients have reported a short-term benefit, long-term follow-up data are limited. We analyzed the long-term clinical outcomes of autologous bone marrow cell infusion (ABMI) for decompensated liver cirrhosis (LC). Patients enrolled in a pilot single-armed ABMI study were followed up more than 5 years. Bone marrow-derived mononuclear cells (BM-MNCs) from decompensated LC were harvested and after processing were infused into a peripheral vein. The laboratory test results and long-term clinical course including liver transplantation (LT), development of cancer, cause of death, and survival after ABMI were analyzed. Nineteen patients were followed up for a median of 66 months after ABMI. Liver function, including serum levels of albumin and Child-Pugh (CP) score, was improved at the 1-year follow-up. Liver volume was significantly greater, cirrhosis was sustained, and collagen content was decreased at the 6-month follow-up. Five years after ABMI, five patients (26.3%) maintained CP class A without LT or death, and five patients (26.3%) had undergone elective LT. Hepatocellular carcinoma (HCC) occurred in five patients (26.3%), and lymphoma and colon cancer occurred in one patient each. Three patients (15.8%) were lost to follow-up at months 22, 31, and 33, respectively, but maintained CP class A until their last follow-up. Five patients expired due to infection. While improved liver function was maintained in some patients for more than 5 years after ABMI, other patients developed HCC. Further studies of long-term follow-up cohorts after cell therapy for LC are warranted.

Background & Aims: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA + -M2BP) can be used to assess the degree of liver fibrosis, but few studies have investigated its prognostic utility. We evaluated whether serum WFA + -M2BP can predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients., Methods: A total of 1323 CHB patients with WFA + -M2BP test results between 2009 and 2011 were included in this retrospective analysis., Results: The mean age of patients (793 men) was 51.0 years. During the follow-up period (median 60.3 months), 52 (3.9%) patients developed HCC. Age, the proportion of male gender, the presence of diabetes and cirrhosis, and levels of aspartate aminotransferase, alpha-foetoprotein, and WFA + -M2BP were significantly greater in patients with HCC than in those without HCC, whereas serum albumin levels and platelet counts were significantly lower in patients with HCC than in those without HCC (all P<.05). In multivariate analysis, WFA + -M2BP level was an independent predictor of HCC development (adjusted hazard ratio 1.143, 95% CI: 1.139-1.829), along with male gender and diabetes (all P<.05). In patients without cirrhosis (n=1087), WFA + -M2BP levels ≥1.8 were associated with a higher risk of HCC development (P<.001 by log-rank test), whereas WFA + -M2BP levels ≥1.8 tended to be associated with a higher risk of HCC development in patients with cirrhosis (n=236) (P=.073 by log-rank test)., Conclusions: WFA + -M2BP level can independently predict HCC development. Further studies should investigate whether WFA + -M2BP level could be incorporated into surveillance strategies for CHB patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Performing repeated liver biopsies to assess the improvement of liver fibrosis is impractical. The purpose of this prospective cohort study was to assess the improvement of liver fibrosis during antiviral treatment by serial liver stiffness (LS) measurement using Fibroscan in chronic hepatitis B (CHB) patients with advanced fibrosis., Methods: Nucleos(t)ide analog-naive CHB patients with advanced fibrosis in histological findings (stage ≥F3), high viral load (hepatitis B virus DNA ≥2,000 IU/ml), and normal liver enzyme levels (<2 × upper normal limit) before starting antiviral treatment were included in this study. LS measurement was performed at baseline and annually for 5 years during antiviral treatment. Five-year fibrosis improvement was defined as LS value <7.2 kPa (

This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: The risk of developing hepatocellular carcinoma (HCC) varies, even in the context of cirrhosis. We investigated the relationship between liver stiffness (LS) in subcirrhotic range, assessed via transient elastography (TE), and risk of HCC development in patients with chronic hepatitis B (CHB)-related cirrhosis., Methods: Data on 540 patients presenting with clinically evident CHB-related cirrhosis between April 2006 and December 2014 were reviewed retrospectively. Subcirrhotic range of LS was defined by TE values ≤13 kPa., Results: Of the study population, 214 (39.6%) had LS values in the subcirrhotic range. During follow-up (median 54.1 months), 81 patients (15.0%) developed HCC. In conjunction with age, male gender, and diabetes mellitus, subcirrhotic LS value (hazard ratio = 0.462) was an independent predictor of HCC development on multivariate analysis (all p < 0.05). Cumulative HCC incidence was significantly lower for patients in subcirrhotic (versus cirrhotic) LS range (log-rank test, p < 0.05). In our cohort, the modified REACH-B score performed better than other prediction models, namely REACH-B, CU-HCC, and LSM-HCC scoring systems (area under receiver operating characteristic curve: 0.717 versus 0.669, 0.578, and 0.624, respectively, for 7-year HCC risk)., Conclusions: A significant association between subcirrhotic range of LS value and lower risk of HCC development was identified in patients with clinically evident CHB-related cirrhosis. Thus, different TE-based HCC surveillance strategies may be required even in patients with identical liver cirrhosis disease category.

Background and Aims: The relationship between liver fibrosis and the occurrence of ischemic stroke is unknown. We investigated the correlation between liver fibrosis assessed with transient elastography (TE) and the risk of ischemic stroke., Methods: Between April 2013 and August 2014, patients with acute ischemic stroke and subjects who underwent a health check-up were included in the study. Liver fibrotic burden was assessed with TE in all participants. The degree of liver fibrosis was compared between groups by using various multiple logistic regression models and propensity-score matched analyses., Results: Two hundred ninety-five patients with ischemic stroke (stroke group) and 1942 subjects with health check-up (control group) were included. The mean liver stiffness (LS) on TE (5.6 vs. 4.1 kPa) and the proportion of significant fibrosis (>8 kPa) (9.2% vs. 1.8%) were significantly higher in the stroke than in the control group (all p<0.05). These trends were observed regardless of body mass index, the degree of hepatic steatosis, and metabolic syndrome (all p<0.05). The adjusted odds ratio (OR) for ischemic stroke was 1.268 (95% confidence intervals [CI] 1.183-1.358) per 1 kPa increase and 12.033 (95% CI 5.180-27.948) for significant fibrosis, compared with no fibrosis (all p < 0.05). Propensity-score matched analysis also confirmed that liver fibrosis was independently associated with the risk of ischemic stroke (OR 1.804 [95% CI 1.461-2.230] per 1 kPa increase, 13.184 [95% CI 3.127-55.645] for significant fibrosis, compared with no fibrosis; all p<0.001)., Conclusions: The degree of liver fibrosis, assessed with TE, was significantly associated with the risk of ischemic stroke., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aim: Liver stiffness (LS) value determined using transient elastography (TE) can be used to assess the degree of liver fibrosis. The study investigated whether TE can predict the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA)., Methods: This study retrospectively enrolled 228 patients with HCC who received TE and RFA as the first-line treatment for HCC between 2008 and 2015. Cox regression analysis was used to identify independent predictors of HCC recurrence., Results: The median age of the study population (170 men and 58 women) was 61 years. During the study period, HCC recurrence and mortality developed in 125 (54.8%) and 37 (16.2%) patients after RFA, respectively. Liver cirrhosis, platelet count, multiple tumors, and LS value were the independent predictors of HCC recurrence. When the study population was stratified into early (< 12 months) and late (≥ 12 months) recurrence groups, LS value was an independent predictor of late recurrence, along with liver cirrhosis and spleen diameter. The risk of late recurrence was higher in patients with LS values of ≥ 13 kPa than in those with LS values of < 13 kPa (adjusted hazard ratio [HR] = 4.507, 95% confidence interval [CI] 2.131-7.724, P < 0.001). Recurrence was the only predictor of overall survival (HR = 18.583, 95% CI 2.424-142.486, P = 0.005)., Conclusions: Findings of this study suggest that LS measurement using TE can be a useful predictor of HCC recurrence after RFA., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The clinical features of hepatocellular carcinoma (HCC) differ in patients with and without cirrhosis., Objective: We aimed to investigate the long-term outcomes of noncirrhotic HCC patients after curative resection., Methods: We retrospectively examined 649 consecutive patients with HCC who underwent curative resection from 1996 to 2012; 387 (59.6%) were cirrhotic and 262 (40.4%) were noncirrhotic., Results: The mean age was 54.7 years, and 511 (78.7%) of the study participants were men. The most common cause of HCC was hepatitis B virus (n = 419, 64.6%). Noncirrhotic tumors were larger and more advanced than cirrhotic tumors. However, the noncirrhotic group showed better disease-free survival (DFS) and overall survival (OS) after resection than the cirrhotic group (median 64.0 vs. 56.0 months for OS and 48.0 vs. 31.0 months for DFS, p < 0.05). The predictors for HCC recurrence were cirrhosis, tumor number, portal vein invasion, and major surgery., Conclusions: Noncirrhotic HCC showed better DFS and OS after resection than cirrhotic HCC, although noncirrhotic HCC presented more aggressively., (© 2017 S. Karger AG, Basel.)

Background & Aims: We performed a propensity-score matched analysis to investigate whether entecavir, compared with lamivudine, can reduce risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B after adjusting for level of fibrosis., Methods: We performed a retrospective study of 1079 patients with chronic hepatitis B who received first-line therapy with lamivudine (n = 435) or entecavir (n = 644) from 2006 through 2013. Only patients with available liver stiffness value measured by transient elastography were recruited. Liver cirrhosis was diagnosed by ultrasonography. To adjust for the imbalance of patients treated with lamivudine versus entecavir, we performed propensity-score matching (PSM), at a ratio of 1:1, using 7 factors (age, sex, hepatitis B e antigen, alanine aminotransferase, serum albumin, platelet count, and liver stiffness; PSM1) or 8 factors (variables of PSM1 plus ultrasonography measurements of cirrhosis; PSM2). Patients with virologic breakthrough or resistance mutations received rescue therapy., Results: Over the 7-year period, 91 patients developed HCC and 104 had liver-related events in the entire cohort. In multivariate analyses, level of fibrosis, but not antiviral regimen, was independently associated with risk of HCC (P < .05). The PSM1 group included 342 pairs of patients and the PSM2 group included 338 pairs. Similar proportions of patients given lamivudine versus entecavir developed HCC in each model (10.5% given lamivudine vs 9.9% given entecavir in PSM1 and 11.9% vs 12.6% in PSM2; all P > .05). When PSM was applied to patients with liver stiffness value ≤13 kPa or >13 kPa, patients given lamivudine versus entecavir still had similar cumulative rates of HCC development (all P > .05)., Conclusions: In a PSM analysis, we associated level of fibrosis, rather than antiviral regimen, with risk of HCC, when patients received appropriate rescue therapy in case of virologic breakthrough or resistance mutations., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the prevalence and the predictors of silent but substantial liver fibrosis in patients with primary Sjogren's syndrome (pSS)., Methods: We enrolled 101 pSS patients with normal liver function and structures, and without significant liver diseases or other conditions affecting liver fibrosis. The European league against rheumatism (EULAR) SS patients reported index (ESSPRI) and the EULAR SS disease activity index (ESSDAI) were analyzed. Liver stiffness (LS) was measured using transient elastography and 7.4 kPa was determined as the cutoff value for significant liver fibrosis., Results: The median age of patients (91women) was 53 years and the median LS value was 4.7 kPa. The median ESSPRI and ESSDAI showed no correlation with LS values. Twelve patients (11.9%) had significant liver fibrosis. In multivariate logistic regression, white blood cells count ≤4000.0/mm(3) (Odds ratio [OR] 9.821), serum albumin ≤3.8 mg/dL (OR 16.770) and aspartate aminotransferase (AST) ≥ 27.0 IU/L (OR 20.858) independently predicted silent but substantial liver fibrosis in pSS patients., Conclusions: The prevalence of silent but substantial liver fibrosis was 11.9% in pSS and its predictors were leukopenia, decreased serum albumin and increased AST levels.

Spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is typically caused by gram-negative bacteria. However, the number of SBP cases due to gram-positive bacteria is steadily increasing. To date, little is known about the predictive factors involved in SBP infections.We performed a retrospective cohort study of patients (>18 years) with SBP due to gram-positive and -negative bacteria who were enrolled from January 2006 to December 2013 at Severance Hospital in Seoul, Korea where the incidences of hepatitis B virus associated chronic liver disease, cirrhosis, and hepatocellular carcinoma are high. Only the 1st SBP episode for each patient within the study period was included in our analysis.We identified 77 patients with cirrhosis and SBP. Of these, 27 patients (35%) had gram-positive bacterial infections and 50 patients (65%) had gram-negative bacterial infections. Our univariate analysis revealed that an early stage of cirrhosis (P = 0.004), lower creatinine level (P = 0.011), lower Sequential Organ Failure Assessment (SOFA) score (P = 0.001), lower Model for End-Stage Liver Disease score (P = 0.005), and use of systemic antibiotics within 30 days before SBP diagnosis (P = 0.03) were significantly associated with gram-positive bacterial infections. Our multivariate analysis indicated that the use of systemic antibiotics within 30 days before SBP diagnosis (odds ratio, 3.94; 95% CI, 1.11-13.96; P = 0.033) and a lower SOFA score (odds ratio, 0.56; 95% CI, 0.37-0.86; P = 0.007) were independent predictive factors of SBP caused by gram-positive bacterial infections in patients with cirrhosis. However, we did not observe a statistically significant difference in the 28-day mortality between the gram-positive and -negative bacterial infection groups (40.7% vs 46.0%, respectively; P = 0.407).In this study, the incidence rate of SBP caused by gram-positive bacteria in patients with cirrhosis was similar to the rates reported in recently published studies. Furthermore, the use of systemic antibiotics within 30 days before SBP diagnosis and a lower SOFA score were significantly associated with SBP caused by gram-positive bacteria in patients with cirrhosis., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background/aims: To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB)., Methods: Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals., Results: We analyzed 105 patients (median age of 47 years). The F0-1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥ F2, ≥ F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3-4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance., Conclusions: Advanced fibrosis stage (F3-4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.

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., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) has a close relationship with coronary atherosclerosis. We investigated the association between coronary atherosclerosis and liver fibrosis, represented as coronary artery calcification (CAC) score, and live stiffness (LS) value assessed using transient elastography (TE), respectively, in patients with NAFLD., Methods: Between January 2013 and March 2014, a total of 285 asymptomatic subjects without chronic liver and ischemic heart diseases who underwent comprehensive medical health check-up were recruited. NAFLD was defined as controlled attenuation parameter (CAP) ≥ 250 dB/m on TE., Results: The median age of the study population (men 161 and women 124) was 56 (interquartile [IQR], 50-63) years. Of these, 142 (49.8%) subjects had NAFLD. Among subjects with NAFLD, CAC score was independently correlated with the male gender (β = 0.230; P = 0.010), elevated erythrocyte sedimentation rate (β = 0.220; P = 0.019), reduced estimated glomerular filtration rate (β=-0.220; P = 0.004), increased left ventricular mass index (β = 0.226; P = 0.027), and higher LS values (β = 0.274; P < 0.001). In addition, alanine aminotransferase level (β = 0.214, P = 0.012) and CAC score (β = 0.311; P = 0.001) are the only independent factors associated with LS values in subjects with NAFLD., Conclusions: Higher CAC score was independently correlated with LS values in subjects with NAFLD. However, it should be further investigated whether TE can be incorporated into a screening tool to identify the high-risk population for coronary artery disease., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background & Aims: Liver fibrosis is a multifactorial disease that can affect the development of cerebral small vessel diseases (SVDs) including cerebral microbleeds (CMBs), leukoaraiosis, and silent infarctions. Transient elastography can accurately assess the degree of liver fibrosis by measuring liver stiffness (LS). In the present study, we investigated the association between SVDs and LS values., Methods: We recruited 300 participants (mean age 56 years, 170 men) who underwent a comprehensive medical health check-up between January 2011 and December 2012. Transient elastography was taken on the right lobe of the liver through intercostal space with patients lying in the dorsal decubitus position with the right arm in maximal abduction. Mild and significant fibrosis were defined as LS values >5.6 and >8.0 kPa, respectively. The presence of each SVD was determined using the FLAIR, GRE MR imaging as well as T1-, T2-weighted MR images. We tested whether the presence and burden of each type of SVD were different by LS values., Results: Of the different types of SVDs, only the presence (p = 0.001) and number of CMBs (p<0.001) were positively associated with LS values. Multivariate analysis revealed that significant fibrosis (>8.0 kPa) was an independent predictor of CMBs (odds ratio 6.079, 95% confidence interval 1.489-24.819, p = 0.012). However, leukoaraiosis and silent infarctions were not associated with LS values (all p>0.05)., Conclusions: The degree of liver fibrosis, as assessed using transient elastography, was independently associated with the presence and burden of CMBs in healthy, asymptomatic participants. Understanding the link between the brain and liver may advance future research on the pathomechanisms of CMBs.

Introduction: Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients., Methods: Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy., Results: Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA., Conclusions: Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA., Funding: Bristol-Myers Squibb.

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 β=0.375, p=0.018) and MSS (standardised β=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.

Unlabelled: Early detection of liver cirrhosis in its subclinical stage is of paramount importance to identify high-risk individuals for developing hepatocellular carcinoma (HCC). This study investigated whether transient elastography (TE) can identify patients with subclinical cirrhosis (SCC) who are at increased risk of developing HCC among chronic hepatitis B (CHB) patients without clinical evidence of cirrhosis. A total of 2,876 CHB patients without clinical cirrhosis who received TE examinations between April 2006 and December 2012 were enrolled in this prospective study. SCC was defined as a nonclinical cirrhosis, but with a liver stiffness (LS) value ≥13 kilopascals (kPa). Mean age of the study population was 46.1 years, and male gender was predominant (n = 1,775; 61.7%). Mean LS value was 7.9 kPa, and SCC was identified in 285 (9.9%) patients. During the median follow-up period of 48.9 months (range, 6.6-96.2), HCC developed in 16 patients (13.3 per 1,000 person-years) in the SCC group and 36 (3.4 per 1,000 person-years) in the non-SCC group. Cumulative incidence rate of HCC in the SCC group was significantly higher than that in the non-SCC group (P < 0.001, log-rank test). On multivariate analysis, SCC was independently associated with a risk of developing HCC, regardless of antiviral therapy (without antiviral therapy: hazard ratio [HR]: 4.680; 95% confidence interval [CI]: 1.187-18.441; P = 0.027; with antiviral therapy: HR, 3.344; 95% CI: 1.526-7.328; P = 0.003)., Conclusion: TE can identify CHB patients with SCC who are at increased risk of developing HCC, even when cirrhosis is not clinically apparent., (© 2015 by the American Association for the Study of Liver Diseases.)

Background: Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis., Aim: We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores., Methods: Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT., Results: A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r (2) = 0.018-0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3-4 and F4 by 5 and 17 %, respectively., Conclusions: ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.

Background & Aims: Few noninvasive methods can accurately identify esophageal varices (EVs) in patients with compensated cirrhosis. We developed and validated a novel, acoustic radiation force impulse (ARFI) elastography-based prediction model for high-risk EVs (HEVs) in patients with compensated cirrhosis., Methods: A total of 143 patients with compensated cirrhosis between February, 2010 and February, 2013 (training set) and 148 between June, 2010 and May, 2013 (validation set) who underwent ARFI elastography and endoscopy were prospectively recruited. Independent predictors of HEVs were used to construct a prediction model., Results: Based on multivariate analysis, we developed two new statistical models, a varices risk score and ARFI-spleen diameter-to-platelet ratio score (ASPS), the latter of which was calculated as ARFI velocity × spleen diameter/platelet count. The area under receiver operating characteristic curve (AUROC) of the varices risk score and ASPS to predict HEVs were 0.935 (95% confidence interval [CI] 0.882-0.970) and 0.946 (95% CI 0.895-0.977), respectively. When ASPS, a simpler model with a higher AUROC, was applied in the validation set, acceptable diagnostic accuracy for HEVs was observed (AUROC = 0.814 [95% CI 0.743-0.885]). To detect HEVs, a negative predictive value of 98.3% was achieved at ASPS <2.83, whereas a positive predictive value of 100% was achieved at ASPS >5.28., Conclusions: ASPS, a novel noninvasive ARFI-based prediction model, can accurately identify HEVs in patients with compensated cirrhosis. ASPS <2.83 may safely rule out the presence of HEVs, whereas patients with ASPS >5.28 should be considered for endoscopic examinations or appropriate prophylactic treatment.

Background: To elucidate the benefits of successful antiviral therapy in chronic hepatitis C (CHC) patients, Methods: A total of 463 CHC patients who underwent pegylated interferon alfa and ribavirin therapy were classified as sustained virological response (SVR) or non-SVR based on response to antiviral therapy. We investigated disease progression to cirrhosis in non-cirrhotic patients, development of cirrhosis-related complications such as ascites, variceal bleeding, and hepatic encephalopathy in patients with cirrhosis, and development of hepatocellular carcinoma (HCC)., Results: Three hundred patients achieved SVR, and 163 were classified into the non-SVR group. The overall SVR rates were 64.8 %, and multivariate analysis showed that younger age, non-cirrhosis, HCV genotype 2 or 3, lower HCV RNA level (<800,000 IU/mL), and lower body weight were independent factors associated with SVR (all P < 0.05). During a median follow-up of 36.1 months, non-cirrhotic patients with SVR had significantly lower risk of progression to cirrhosis compared with patients with non-SVR (P < 0.001). Moreover, SVR was related to a reduced risk of HCC development (P = 0.017)., Conclusions: SVR resulted in significantly more favorable long-term outcomes, such as lower risk of progression to cirrhosis and HCC occurrence compared with non-SVR.

Aim: To investigate the prevalence of significant liver fibrosis assessed using transient elastography (TE) and its predictors in asymptomatic general population., Methods: A total of 159 subjects without chronic viral hepatitis who underwent comprehensive medical health check-up between January 2012 and July 2012 were prospectively recruited. Significant liver fibrosis was defined as liver stiffness value>7.0 kPa., Results: The mean age and body mass index (BMI) of the study population (men 54.7%) was 56.0 years and 24.3 kg/m2. Among the study subjects, 11 (6.9%) showed significant liver fibrosis. On univariate analysis, BMI, alanine aminotransferase (ALT), homeostasis model assessment of insulin resistance, carotid intimal media thickness (IMT), number of calcified plaques on carotid ultrasound, and visceral fat area on computed tomography were significantly higher in subjects with significant liver fibrosis than in those without (all P<0.05). However, on multivariate analysis, BMI [odds ratio (OR)=.487; P=0.045], ALT (OR=1.078; P=0.014), carotid IMT (OR=3.244; P=0.027), and the number of calcified carotid plaques (OR=1.787; P=0.031) were independent predictors of significant liver fibrosis., Conclusion: The prevalence of significant liver fibrosis assessed using TE was 6.9% in apparently healthy subjects. High BMI, high ALT, thicker carotid IMT, and higher numbers of calcified carotid plaques were independently associated with the presence of significant liver fibrosis.