Kyu Sik Jung

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

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. (HEPATOLOGY 2011)

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.

Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis.

Background Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis. Methods Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis (≥F3) with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) and hepatocellular carcinoma (HCC). Results The mean age of the patient (72 men, 56 women) was 52.2 years. During the median follow-up period [median 27.8 (12.6–61.6) months], LREs developed in 19 (14.8%) patients (five with hepatic decompensation, 13 with HCC, one with both). Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P<0.044; hazard ratio (HR), 1.038; 95% confidence interval (CI), 1.002–1.081]. When the study population was stratified into two groups using the optimal cutoff value (19 kPa), which maximized the sum of sensitivity (61.1%) and specificity (86.2%) from a time-dependent receiver operating characteristic curve, patients with LSM>19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257–22.812; P = 0.001). Conclusion LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis.

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

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).

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.

Clinical applications of transient elastography

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan®) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.

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.

Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea

BACKGROUND/AIMS The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. METHODS We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). RESULTS Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. CONCLUSIONS Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.

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

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.(Hepatology 2015;62:1757–1766)

Factors Affecting the Accuracy of Controlled Attenuation Parameter (CAP) in Assessing Hepatic Steatosis in Patients with Chronic Liver Disease

Background & Aims Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP. Methods A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 (<5%), S1 (5–33%), S2 (34–66%), and S3 (>66% of hepatocytes). Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥S1, ≥S2, and S3). Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP. Results The median age (102 males and 59 females) was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI) and interquartile range/median of CAP value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207–75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006–1.034; P = 0.006) were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level. Conclusions Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.