High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis.

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.

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.

BACKGROUND & AIMS: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. METHODS: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. RESULTS: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively. CONCLUSIONS: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. LAY SUMMARY: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

Improvement of Liver Fibrosis after Long-Term Antiviral Therapy Assessed by Fibroscan in Chronic Hepatitis B Patients With Advanced Fibrosis.

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 (

Conventional versus drug-eluting beads chemoembolization for hepatocellular carcinoma: Emphasis on the impact of tumor size.

BACKGROUND AND AIM: This study aims to evaluate clinical outcomes of patients with hepatocellular carcinoma who underwent transarterial chemoembolization (TACE) using drug-eluting beads (DEB). PATIENTS AND METHODS: This study retrospectively compared the clinical outcomes of 250 consecutive patients who underwent DEB-TACE (n = 106) or conventional TACE (cTACE) (n = 144) in a tertiary center between January 2010 and April 2014. The median age of the patients was 62 years and 81.6% were men. The primary endpoint was overall survival (OS). The time to progression (TTP), radiological response rate using modified response evaluation criteria in solid tumors criteria at 1 month after treatment, and complication rates within 1 month were also compared. RESULTS: The most common etiology was hepatitis B virus infection. The median index tumor size was 2.8 cm, and 150 (60.0%) patients had Barcelona Clinic Liver Cancer stage B. Median TTP in the cTACE group was longer than in the DEB-TACE group (13.3 vs10.8 months; P = 0.023). However, DEB-TACE and cTACE groups showed no significant differences for mean OS (46.6 vs 44.9 months; P = 0.660) and disease control rate at 1 month (78.3% vs 86.8%; P = 0.076). The OS, TTP, and disease control rate were also not different between two groups, even when subgrouped by index tumor size. The complication rates within 1 month were higher in the cTACE group (6.6% vs 14.6%; P = 0.048). CONCLUSIONS: Drug-eluting beads TACE appears to be a safe intra-arterial therapy. However, it is not superior to cTACE in terms of efficacy. Tumor size might not be a criterion to select treatment modality between cTACE and DEB-TACE in terms of efficacy.

Validation of hepatitis B virus-related hepatocellular carcinoma prediction models in the era of antiviral therapy.

UNLABELLED: Several risk prediction models have been created to predict hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) occurrence, with promising results. However, their prognostic performances need to be validated in the era of antiviral therapy. From 2006 to 2011, patients with chronic HBV infection were recruited and those with a history of HCC or hepatic decompensation were excluded. At enrollment, liver stiffness (LS) was measured using transient elastography. We assessed the performances of conventional HCC prediction models (CU-HCC, GAG-HCC, REACH-B, and LSM-HCC scores) and the modified REACH-B (mREACH-B) score where LS values were incorporated into REACH-B score instead of serum HBV-DNA levels. Of 1,308 subjects analyzed, the median age was 50.0 years (883 men). During the follow-up (median, 75.3 months), HCC developed in 125 (9.6%) patients. mREACH-B score had the highest areas under the receiver operating characteristic curves (AUROCs) for the prediction of HCC development at 3/5 years (0.828/0.806), compared with LSM-HCC (0.777/0.759), GAG-HCC (0.751/0.757), REACH-B (0.717/0.699), and CU-HCC (0.698/0.700) scores, respectively, with statistical significances (all P values <0.05 vs. mREACH-B). When serum HBV-DNA levels were excluded from the formula for REACH-B score, AUROCs for HCC development at 3/5 years improved paradoxically (from 0.717/0.699 to 0.757/0.732, respectively). In patients with antiviral therapy (n = 848), mREACH-B score had the better prognostic performances for HCC development at 3/5 years, compared to other prediction models. However, in patients without antiviral therapy (n = 460), it had the prognostic performances comparable to those of other prediction models. CONCLUSIONS: Prognostic performances of mREACH-B score seemed better compared to conventional models. In the era of antiviral therapy, incorporation of serum HBV-DNA level should be applied cautiously and individual risks should be assessed effectively based on the fibrotic burden.

Entecavir plus tenofovir combination therapy in patients with multidrug-resistant chronic hepatitis B: results of a multicentre, prospective study.

BACKGROUND & AIMS: Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis B (CHB) treatment. We evaluated the antiviral efficacy and safety of entecavir (ETV) plus tenofovir (TDF) combination therapy in multidrug-resistant (MDR) CHB patients. METHODS: In this prospective, multicentre study, MDR CHB patients, defined as measurable serum HBV DNA (≥60 IU/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with ETV 1.0 mg and TDF 300 mg combination therapy for 48 weeks. RESULTS: A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2-6) were included. At baseline, median age was 47.0 years, 89.1% were HBeAg(+), and median HBV DNA was 4.24 (range, 2.11-6.73) log10 IU/ml. By week 4, 12, 24 and 48, 15/64 (23.4%), 36/64 (56.3%), 43/64 (67.2%) and 55/64 (85.9%) patients achieved a HBV DNA <60 IU/ml respectively. The mean reduction of HBV DNA from baseline to 4 and 48 weeks was 1.23 log10 IU/ml and 2.38 log10 IU/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to TDF or novel mutation was detected in any patients. CONCLUSIONS: In difficult-to-treat MDR CHB patients with a high exposure to multiple antiviral drugs, ETV plus TDF combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.

Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients.

OBJECTIVE: As data on the effectiveness of tumor markers in detecting hepatocellular carcinoma (HCC) in cirrhotic patients are limited, we investigated the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3). MATERIAL AND METHODS: This retrospective study enrolled 361 cirrhotic patients with HCC, and 276 cirrhotic patients without HCC occurrence. RESULTS: Most patients were men (n = 431, 67.7%); the median age was 57.0 years. The main etiology of chronic liver disease was chronic hepatitis B (n = 467, 73.3%). The sensitivity and specificity of combined three biomarkers was 87.0 and 60.1% in overall HCC, and 75.7 and 60.1% in early HCC, respectively (cutoff: 20 ng/mL for AFP, 40 mAU/mL for PIVKA-II, and 5% for AFP-L3). The area under the receiver operating characteristic curve (AUROC) for HCC diagnosis was 0.765 (95% confidence interval [CI], 0.728-0.801) for AFP; 0.823 (95% CI, 0.791-0.854) for PIVKA-II; and 0.755 (95% CI, 0.718-0.792) for AFP-L3. The AUROC for early HCC diagnosis was 0.754 (95% CI, 0.691-0.816) for AFP, 0.701 (95% CI, 0.630-0.771) for PIVKA-II, and 0.670 (95% CI, 0.596-0.744) for AFP-L3. Combining the three tumor markers increased the AUROC to 0.877 (95% CI, 0.851-0.903) for HCC diagnosis, and 0.773 (95% CI, 0.704-0.841) for early HCC diagnosis. CONCLUSION: Diagnostic accuracy improved upon combining the AFP, PIVKA-II, and AFP-L3 tumor markers compared to each marker alone in detecting HCC and early HCC in cirrhotic patients.

Noninvasive Prediction of Erosive Esophagitis Using a Controlled Attenuation Parameter (CAP)-Based Risk Estimation Model.

BACKGROUND: Erosive esophagitis and fatty liver share obesity and visceral fat as common critical pathogenesis. However, the relationship between the amount of hepatic fat and the severity of erosive esophagitis was not well investigated, and there is no risk estimation model for erosive esophagitis. AIM: To evaluate the relationship between the amount of hepatic fat and the severity of erosive esophagitis and then develop a risk estimation model for erosive esophagitis. METHODS: We enrolled 1045 consecutive participants (training cohort, n = 705; validation cohort, n = 340) who underwent esophagogastroduodenoscopy and CAP. The relationship between severity of fatty liver and erosive esophagitis was investigated, and independent predictors for erosive esophagitis that have been investigated through logistic regression analyses were used as components for establishing a risk estimation model. RESULTS: The prevalence of erosive gastritis was 10.7 %, and the severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation (P < 0.05). A CAP-based risk estimation model for erosive esophagitis using CAP, Body mass index, and significant alcohol Drinking as constituent variables was established and was dubbed the CBD score (AUROC = 0.819, range 0-11). The high-risk group (CBD score ≥3) showed significantly higher risk of having erosive esophagitis than the low-risk group (CBD score <3) (24.1 vs. 2.7 %, respectively; P < 0.001). The diagnostic accuracy of CBD score was maintained in the validation cohort (AUROC = 0.848). CONCLUSION: The severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation, and the CBD score might be a simple CAP-based risk model for predicting erosive esophagitis.

Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008-2011).

BACKGROUND & AIMS: Although sarcopaenia is associated with obesity-related comorbidities, its influence on non-alcoholic fatty liver disease (NAFLD) or steatohepatitis has not been fully determined. We aimed to investigate the direct relationship between sarcopaenia and NAFLD or steatohepatitis in the general population. METHODS: We conducted a cross-sectional study using nationally representative samples of 15,132 subjects from the Korea National Health and Nutrition Examination Surveys 2008-2011. Subjects were defined as having NAFLD when they had higher scores from previously validated NAFLD prediction models such as the hepatic steatosis index, comprehensive NAFLD score and NAFLD liver fat score. BARD and FIB-4 scores were used to define advanced fibrosis in subjects with NAFLD. The skeletal muscle index (SMI) [SMI(%)=total appendicular skeletal muscle mass (kg)/weight (kg)×100] measured by dual-energy X-ray absorptiometry was used to diagnose sarcopaenia with cut points of 32.2% for men and 25.5% for women. RESULTS: SMI was inversely correlated with all NAFLD predicting scores (Ps<0.001). After stratification, sarcopaenic subjects had an increased risk of NAFLD regardless of obesity (odds ratios [ORs]=1.55 to 3.02, depending on models; all Ps<0.001) or metabolic syndrome (ORs=1.63 to 4.00, all Ps<0.001). Multiple logistic regression analysis also demonstrated this independent association between sarcopaenia and NAFLD after adjusting for confounding factors related to obesity or insulin resistance (ORs=1.18 to 1.22, all Ps<0.001). Furthermore, among the NAFLD population, subjects with lower SMIs were likely to have advanced fibrosis compared with non-sarcopaenic individuals (BARD and FIB-4: ORs=1.83 and 1.69, respectively; both Ps<0.001). Compared with non-exercised subjects, individuals who exercised regularly had a lower risk of NAFLD (p<0.001), particularly among obese people with well-preserved muscle mass. CONCLUSIONS: Sarcopaenia is associated with increased risks of NAFLD and advanced fibrosis, independent of obesity or metabolic control.

Lower incidence of hepatocellular carcinoma and cirrhosis in hepatitis C patients with sustained virological response by pegylated interferon and ribavirin.

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.

Normal controlled attenuation parameter values: a prospective study of healthy subjects undergoing health checkups and liver donors in Korea.

BACKGROUND/AIMS: The controlled attenuation parameter (CAP) is a noninvasive method of assessing hepatic steatosis. We defined the normal range of CAP values in healthy subjects and evaluated the associated factors. METHODS: CAP values were measured in a cohort of healthy subjects who were screened as living liver transplantation donors and those who underwent health checkups. Subjects with current or a history of chronic liver disease, abnormalities on liver-related laboratory tests, or fatty liver on ultrasonography or biopsy were excluded. RESULTS: The mean age of the 264 recruited subjects (131 males and 133 females; 76 potential liver donors and 188 subjects who had undergone health checkups) was 49.2 years. The mean CAP value was 224.8 ± 38.7 dB/m (range 100.0-308.0 dB/m), and the range of normal CAP values (5th-95th percentiles) was 156.0-287.8 dB/m. The mean CAP value was significantly higher in the health checkup than in the potential liver donor group (227.5 ± 42.0 vs. 218.2 ± 28.3 dB/m, P = 0.040). CAP values did not differ significantly according to gender or age in either group (all P > 0.05). In a multivariate linear regression analysis, body mass index (ß = 0.271, P = 0.024) and triglyceride levels (ß = 0.348, P = 0.008) were found to be independently associated with CAP values. CONCLUSION: We determined the normal range of CAP values and found that body mass index and triglyceride levels were associated with the CAP values of healthy subjects.

Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)-related HCC after curative resection. METHODS: Patients with HBV-related HCC who underwent curative resection and showed Laennec stage 3 to 4 were enrolled and the cases with stage 4 were subclassified histologically into three groups (stages 4A, 4B and 4C) according to the Laennec system. Between February 2006 and August 2009, 92 patients were recruited. RESULTS: Stage 3, 4A, 4B and 4C were identified in 24 (26.1%), 15 (16.3%), 43 (46.7%) and 10 (10.9%) patients respectively. The cumulative incidence rates of recurrence at 1, 2 and 3 years were 24.2%, 40.5% and 55.1% respectively. On multivariate analysis, serum albumin [hazard ratio (HR), 0.528; 95% confidence interval (CI), 0.312-0.891; P=0.017] and Edmondson-Steiner grade III-IV (HR, 3.456; 95% CI, 1.123-10.517; P=0.031) were significantly correlated with early recurrence (<1 year), whereas stage 4C (HR, 5.426; 95% CI, 1.030-28.598; P=0.046) was the only independent risk factor for late recurrence (≥1 year). CONCLUSIONS: Histological subclassification of cirrhosis using the Laennec system is a significant predictor of late recurrence in patients with HBV-related HCC after curative resection.

Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population.

BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method of measuring hepatic steatosis using a process based on transient elastography. We investigated the diagnostic accuracy of CAP in detecting hepatic steatosis in patients with chronic liver disease (CLD). METHODS: A total of 135 patients with CLD who underwent liver biopsy and CAP were consecutively enrolled in this prospective study. The performance of CAP for detection of hepatic steatosis compared with liver biopsy was calculated using area under receiver operating characteristics curves (AUROC). Steatosis was categorized into S0 (<5%), S1 (5-33%), S2 (34-66%) and S3 (>66% of hepatocytes). RESULTS: Male gender predominated (n = 87, 64%) and the median age was 51 years. The aetiologies of CLD included non-alcoholic fatty liver disease (n = 56, 41.5%) and chronic viral hepatitis because of hepatitis B (n = 47, 34.8%) and C (n = 12, 8.9%). Steatosis repartition was: S0 31.1% (n = 42), S1 43.7% (n = 59), S2 18.5% (n = 25) and S3 6.7% (n = 9) respectively. In the multivariate analysis, steatosis grade and body mass index were independently associated with CAP (all P < 0.001), whereas fibrosis stage and activity grade were not. The AUROCs of CAP were 0.885 for ≥S1 (sensitivity 73.1%, specificity 95.2%), 0.894 for ≥S2 (sensitivity 82.4%, specificity 86.1%) and 0.800 for S3 (sensitivity 77.8%, specificity 84.1%). The optimal cut-off CAP values that maximized the Youden index were 250 dB/m (≥S1), 299 dB/m (≥S2), and 327 dB/m (=S3) respectively. CONCLUSIONS: Our data showed that CAP had high diagnostic accuracy for detecting hepatic steatosis in patients with CLD and suggested that CAP is also applicable for Asian patients.

Community-acquired vs. nosocomial spontaneous bacterial peritonitis in patients with liver cirrhosis.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with end-stage liver disease, but reports comparing community-acquired SBP (CA-SBP) with nosocomial SBP (N-SBP) are rare. This study compared the clinical characteristics, microbiological characteristics, and treatment outcomes of patients with CA-SBP and N-SBP. METHODOLOGY: Records for 248 patients (173 men, 75 women) with cirrhosis who experienced SBP were retrospectively reviewed. RESULTS: The study population included 202 (81.5%) patients with CA-SBP and 46 (18.5%) patients with N-SBP. Patients with CA-SBP or N-SBP showed no significant differences in baseline or microbiological characteristics, except for a high frequency of previous SBP history in the N-SBP population (P=0.020). During hospitalization, antibiotic switching and in-hospital mortality were significantly higher for patients with N-SBP than CA-SBP (35.6% vs. 8.9%; P=0.001 and 30.4% vs. 12.9%; P=0.028). There were 202 (81.5%) deaths during the follow-up period, with longer overall survival time in patients with CA-SBP (7.9 vs. 3.9 months; P=0.041). However, time to recurrence was not significantly different between the two groups (4.7 vs. 3.6 months; P=0.910). CONCLUSIONS: N-SBP was significantly associated with increased antibiotic switching, higher in-hospital mortality and shorter overall survival. Third-generation cephalosporin may be inappropriate as first-line empirical antibiotics for patients with N-SBP.

Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan).

UNLABELLED: Liver stiffness measurement (LSM) using FibroScan accurately assesses the degree of liver fibrosis and the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. This study investigated the usefulness of LSM as a predictor of HCC development in patients with chronic hepatitis B (CHB). A total of 1,130 patients with non-biopsy-proven CHB who underwent LSM between May 2005 and December 2007 were enrolled in this prospective study. After LSM was performed, patients attended regular follow-up as part of a surveillance program for the detection of HCC. The mean age of the patients (767 men, 363 women) was 50.2 years, and the median LSM was 7.7 kPa. Six hundred seventy-two (59.5%) patients received antiviral treatment before or after enrollment. During the follow-up period (median, 30.7 months; range, 24.0-50.9 months), HCC developed in 57 patients (2.0% per 1 person-year). The 1-, 2-, and 3-year cumulative incidence rates of HCC were 0.80%, 3.26%, and 5.98%, respectively. On multivariate analysis, together with old age, male sex, heavy alcohol consumption (>80 g/day), serum albumin, and hepatitis B e antigen positivity, patients with a higher LSM (>8 kPa) were at a significantly greater risk of HCC development, with the following hazard ratios: 3.07 (95% confidence interval [CI], 1.01-9.31; P = 0.047) for LSM 8.1-13 kPa; 4.68 (95% CI, 1.40-15.64; P = 0.012) for LSM 13.1-18 kPa; 5.55 (95% CI, 1.53-20.04; P = 0.009) for LSM 18.1-23 kPa; and 6.60 (95% CI, 1.83-23.84; P = 0.004) for LSM >23 kPa. CONCLUSION: Our data suggest that LSM could be a useful predictor of HCC development in patients with CHB.

Prediction of recurrence after curative resection of hepatocellular carcinoma using liver stiffness measurement (FibroScan®).

BACKGROUND: The purpose of this study was to investigate whether preoperative liver stiffness measurement (LSM) can predict recurrence after curative resection of hepatocellular carcinoma (HCC). LSM using FibroScan(®) can assess the severity of liver fibrosis, which is significantly associated with recurrence after curative resection of HCC. METHODS: Between February 2006 and March 2009, 133 patients who underwent preoperative LSM and curative resection for HCC were enrolled in this prospective study. LSM values were analyzed for association with recurrence, together with other clinical variables. RESULTS: The mean age of the patients (117 men and 16 women) was 57 years. During the follow-up period (median, 25.0 (range, 3.0-54.6) months), HCC recurred in 62 (46.6 %) patients. In multivariate analysis, together with satellite nodule and Edmonson-Steiner grade III-IV, LSM was selected as an independent predictor of recurrence (P < 0.05; hazard ratio, 1.034; 95 % confidence interval, 1.007-1.061). When the study population was stratified into two groups using the optimal cutoff value (13.4 kPa) that maximized the sum of sensitivity (64.7 %) and specificity (76.1 %) from time-dependent receiver operating characteristic curves (area under the receiver operating characteristic curve = 0.676), patients with LSM values >13.4 kPa were at a significantly greater risk for recurrence with a hazard ratio of 1.925 (P = 0.01; 95 % confidence interval, 1.17-3.168) compared with those with LSM values ≤ 13.4 kPa. CONCLUSIONS: Our data suggest that LSM can be a useful predictor of recurrence after curative resection of HCC.

The accuracy of noninvasive methods in predicting the development of hepatocellular carcinoma and hepatic decompensation in patients with chronic hepatitis B.

BACKGROUND: Liver stiffness measurement (LSM) using transient elastography (FibroScan) can accurately assess the degree of liver fibrosis and predict the development of hepatocellular carcinoma (HCC) and variceal bleeding in patients with chronic hepatitis B (CHB). AIMS: We compared the accuracy of noninvasive liver fibrosis prediction methods in predicting the development of HCC or hepatic decompensation in patients with CHB. METHODS: A total of 1126 patients with CHB who underwent LSMs and attended regular follow-ups to detect the development of HCC and hepatic decompensations (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatorenal syndrome) were enrolled. Noninvasive liver fibrosis prediction methods included, age-spleen-to-platelet ratio index, LSM, LSM-spleen diameter-to-platelet ratio index (LSPI), P2/MS, and FIB-4. RESULTS: During follow-up (median, 30.7 mo), HCC and hepatic decompensation developed in 63 and 68 patients, respectively. The accuracy of LSM and LSPI in predicting the development of HCC or hepatic decompensation was higher than that of aspartate aminotransferase-to-platelet ratio index, age-spleen-to-platelet ratio index, P2/MS, or FIB-4 (areas under the receiver operating characteristic curve=0.789 and 0.788 vs. 0.729, 0.756, 0.696, and 0.744 for HCC development; areas under the receiver operating characteristic curve=0.820 and 0.848 vs. 0.787, 0.799, 0.812, and 0.784 for hepatic decompensation). On multivariate analyses, LSM and LSPI were identified as independent predictors of the development of HCC [hazard ratio (HR), 1.040 (LSM); HR, 1.001 (LSPI)] and hepatic decompensation [HR, 1.033 (LSM); HR, 1.002 (LSPI)]. CONCLUSIONS: Our results suggest that LSM or LSPI may be useful predictors of the development of HCC and hepatic decompensation in patients with CHB.

Effects of Entecavir and Tenofovir on Renal Function in Patients with Hepatitis B Virus-Related Compensated and Decompensated Cirrhosis.

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.

Transarterial Radioembolization Versus Concurrent Chemoradiation Therapy for Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

PURPOSE: It is unclear whether the efficacy and safety of concurrent chemoradiation therapy (CCRT) and transarterial radioembolization (TARE) with 90Y are comparable in patients with locally advanced hepatocellular carcinoma. METHODS AND MATERIALS: In total, 209 treatment-naive patients with stage B or C cancer according to the Barcelona Clinic Liver Cancer classification who were treated with TARE or CCRT were analyzed. Propensity scores were calculated and matched at a 1:1 ratio for TARE versus CCRT using age, tumor size, tumor number, portal vein thrombosis, and Barcelona Clinic Liver Cancer staging. In the CCRT group, concurrent hepatic arterial infusion chemotherapy with 5-fluorouracil was delivered at a dosage of 500 mg/d during the first and last 5 days of radiation therapy (median, 45 Gy). Overall survival, freedom from progression, tumor response, and complication rate were compared between the TARE and CCRT groups. RESULTS: Among 209 patients, 124 (62 undergoing TARE and 62 undergoing CCRT) were selected after propensity score matching. Overall survival (TARE vs CCRT, 14.0 months vs 13.2 months, P=.435) and freedom from progression (6.9 months vs 7.8 months, P=.437) were comparable between the 2 groups. Objective response rates at 1 month after treatment were higher for CCRT than for TARE (46.8% vs 16.1%, P<.001), while objective response rates at 3 months were significantly higher for TARE than for CCRT (39.3% vs 21.4%, P=.04). There was no significant difference in long-term response rates (at 6 months and 1 year) between the 2 groups. The CCRT group experienced a higher rate of curative resection or liver transplantation after treatment than the TARE group, although the statistical significance was marginal (24.2% vs 11.3%, P=.060). Treatment-related complications were less frequent after TARE than after CCRT. CONCLUSIONS: Both treatments yielded comparable survival rates and long-term response rates in patients with intermediate- or advanced-stage hepatocellular carcinoma. The role of these modalities as a bridge to curative therapy requires further investigation.