Beom Kyung Kim

A Liver Stiffness Measurement-Based, Noninvasive Prediction Model for High-Risk Esophageal Varices in B-Viral Liver Cirrhosis

OBJECTIVES:Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs and (2) small EVs with red sign or decompensated cirrhosis) are currently recommended for all cirrhotic patients. However, if a simple, noninvasive test is available, many low-risk patients may safely avoid endoscopy. We developed and validated a new liver stiffness measurement (LSM)-based prediction model for HEVs.METHODS:We prospectively enrolled 280 consecutive B-viral cirrhosis patients from 2005 to 2007 (training set) and 121 from 2007 to 2008 (validation set). All underwent laboratory workups, endoscopy, LSM, and ultrasonography. For detection of HEVs, univariate and multivariate analysis were performed, using χ2-test/t-test and logistic regression, respectively. A prediction model was derived from multivariate predictors.RESULTS:In the training set, 90 had HEVs, and multivariate analysis showed significant differences in LSM, spleen diameter, and platelet count between patients with and without HEVs. We developed LSM-spleen diameter to platelet ratio score (LSPS): LSM × spleen diameter/platelet count. The area under the receiver-operating characteristic curve (AUROC) in the training set was 0.954. At LSPS<3.5, 94.0% negative predictive value (NPV) was provided (184 patients), whereas 94.2% positive predictive value (PPV) was achieved (69 patients) at LSPS>5.5. Overall, the likelihood of HEVs was correctly diagnosed in 253 patients (90.3%). Its predictive values were maintained at similar accuracy in subsequent validation set (AUROC=0.953; 94.7% NPV/93.3% PPV at cutoff 3.5/5.5, respectively).CONCLUSIONS:LSPS is a reliable, noninvasive method for detection of HEVs. Patients with LSPS<3.5 may avoid endoscopy safely, whereas those with LSPS>5.5 should be considered for appropriate prophylactic treatments.

Validation of FIB‐4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus‐infected patients

Backgrounds: To optimize management and predict long‐term clinical courses in patients with chronic hepatitis B (CHB), noninvasive tests to determine the degree of hepatic fibrosis have been developed.

Noninvasive models to predict liver cirrhosis in patients with chronic hepatitis B

Objectives: Few noninvasive models of chronic hepatitis B (CHB) to predict liver cirrhosis have been studied. The aim of the current study is to investigate the diagnostic accuracy of two simple novel models of spleen–platelet ratio index (SPRI) and age–spleen–platelet ratio index (ASPRI) in patients with CHB.

Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection

Background: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence.

HBV genotypes: relevance to natural history, pathogenesis and treatment of chronic hepatitis B.

Although chronic HBV infection is the leading cause of chronic liver disease and death worldwide, there are substantial differences in its clinical courses regarding prevalence, mode of transmission, characteristics of each phase, responses to antiviral therapy, and development of cirrhosis and hepatocellular carcinoma, according to geographical areas (Asia versus Western Europe and North America versus Africa). Furthermore, the clinical course in infected individuals depends on a complex interplay among various factors including viral, host, environmental and other factors. Recently, understanding of molecular characteristics of the prevailing HBV genotypes, frequently accompanied mutations and their clinical implications might explain these geographical differences more pertinently. Hence, in this article, we review the global epidemiology and the natural history of HBV infection, with emphasis on summarizing the different HBV genotypes according to regions.

What are ‘true normal’ liver stiffness values using FibroScan®?: a prospective study in healthy living liver and kidney donors in South Korea

Aims: To identify the normal range of liver stiffness (LS) values by recruiting healthy living liver and kidney donors in South Korea.

Applicability of BCLC stage for prognostic stratification in comparison with other staging systems: single centre experience from long-term clinical outcomes of 1717 treatment-naïve patients with hepatocellular carcinoma

The most informative staging system regarding survival outcomes for treatment‐naïve hepatocellular carcinoma (HCC) remains debated. We evaluated prognostic values of Barcelona Clinic Liver Cancer (BCLC) stage compared with other staging systems, and identified discrepancies between treatment options chosen in Korean clinical practice and BCLC guidelines.

Prospective Validation of ELF Test in Comparison with Fibroscan and FibroTest to Predict Liver Fibrosis in Asian Subjects with Chronic Hepatitis B

Background and Aims Liver stiffness measurement (LSM) and FibroTest (FT) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB) patients. Methods Between June 2010 and November 2011, we prospectively enrolled 170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The Batts system was used to assess fibrosis stages. Results Areas under receiver operating characteristic curves (AUROCs) to predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881 for FT. AUROCs to predict F≥2 were similar between each other, whereas LSM and FT had better AUROCs than ELF for predicting F≥3 (both p<0.05), and LSM predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F≥2, F≥3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients, respectively, were correctly classified according to histological results. Conclusions ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients, especially in predicting F≥2. However, LSM consistently provided better performance for predicting F≥3 and F4.

Prospective comparison of prognostic values of modified Response Evaluation Criteria in Solid Tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation.

BACKGROUNDS European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number of target lesions (all versus ≤2) and calculation method (bidimensional versus unidimensional). We compared prognostic values of mRECIST for predicting overall survival (OS) with reference to EASL criteria in treatment-naïve HCC undergoing trans-arterial chemoembolisation (TACE). METHODS The ability to predict OS during longitudinal follow-up was expressed as C-index, and a sample size of 292 patients was required to validate its equivalence between each criteria. Treatment responses were assessed using both guidelines 4weeks after the first TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan-Meier and Cox regression analyses were used to explore differences in OS between responders (complete or partial) and non-responders (stable or progressive disease), defined by each method. RESULTS C-index for EASL and mRECIST guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between two methods. Differences in median OS between responders and non-responders were statistically significant for both EASL (30.1 versus 18.7 months, p<0.001) and mRECIST (33.8 versus 17.1 months, p<0.001) guidelines. In addition to radiological response, α-fetoprotein (p<0.001), tumour number (p<0.001) and tumour size (p=0.048) were significant predictors of OS. In multivariate analysis, radiological criteria, tumour number and α-fetoprotein were identified as independent predictors (all p<0.05). CONCLUSION mRECIST, a simpler method, provided prognostic values for predicting OS equivalent to EASL criteria in patients with HCC undergoing TACE as an initial treatment modality.

Risk assessment of esophageal variceal bleeding in B-viral liver cirrhosis by a liver stiffness measurement-based model

OBJECTIVES:Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs (HEVs; (i) medium/large EVs and (ii) small EVs with red sign or decompensated cirrhosis) are recommended for cirrhotic patients. We assessed cumulative risks of future EV bleeding (EVB) using the liver stiffness measurement (LSM)-based model, LSM–spleen diameter to platelet ratio score (LSPS=LSM×spleen diameter/platelet count).METHODS:We prospectively enrolled 577 consecutive B-viral cirrhosis patients from 2005 to 2009, none of whom experienced EVB. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. Those with HEVs took nonselective β-blockers as prophylaxis for EVB after diagnosis, if not contraindicated. The major end point was the first EVB event, examined using Kaplan–Meier and Cox-regression methods.RESULTS:Among whole population, 95.9% negative- /93.5% positive-predictive value by LSPS<3.5/LSPS≥5.5 were provided for predicting the presence of HEV at enrollment, respectively. Among patients with HEV (n=150), 25 experienced their first EVBs during follow-up (median, 29 months). To differentiate EVB risk, we divided them into subgroup 1 (LSPS<6.5) and 2 (LSPS≥6.5) according to LSPS 6.5, a point with maximum sum of sensitivity and specificity from time-dependent receiver-operating characteristic (ROC) curves (area under ROC curve=0.929). EVB risk was higher in subgroup 2 than subgroup 1 (P<0.001). Multivariate analysis found higher LSPS (P=0.003) a significant predictor, alongside large variceal sizes (P=0.004) and Child-Pugh classifications B/C (P=0.001). Notably, EVB risk of subgroup 1 was as low as that of low-risk EVs (P=0.507).CONCLUSIONS:LSPS is a reliable predictor for EVB risk. According to risk stratification, different prophylactic treatments should be considered for subgroups with LSPS≥6.5.