Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

GOALS: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Risk assessment of development of hepatic decompensation in histologically proven hepatitis B viral cirrhosis using liver stiffness measurement.

BACKGROUND/AIMS: There are few studies regarding the predictive value of liver stiffness measurement (LSM) for development of hepatic decompensation. We assessed the risk of hepatic decompensations in B-viral compensated cirrhosis, using an LSM and LSM-based model (LSM-spleen diameter to platelet ratio score, LSPS = LSM × spleen diameter/platelet count) in a prospective, longitudinal study. METHODS: We analyzed 217 patients with histologically proven B-viral cirrhosis, well-preserved liver function, and no history of decompensation. The Kaplan-Meier and Cox regression method were used to examine the major endpoint, time to the first decompensation event, defined as development of ascites, hepatic encephalopathy, variceal hemorrhage, and deterioration of liver function to Child-Pugh class B/C. RESULTS: During follow-up, 26 patients experienced hepatic decompensation, ascites (n = 22), hepatic encephalopathy (n = 11), variceal hemorrhage (n = 9), and deterioration of liver function (n = 20). For risk stratification, patients were grouped as LSM <13, 13-18, and ≥18 kPa, and from multivariate analysis, patients with LSM 13-18 kPa [hazard ratio (HR) 4.547/ p = 0.044] and ≥18 kPa (HR 12.446/p < 0.001) retained independently higher risks than patients with LSM <13 kPa. Similarly, when patients were grouped as LSPS <1.1, 1.1-2.5, and ≥2.5, those with LSPS 1.1-2.5 (HR 5.796/p = 0.004) and ≥2.5 (HR 13.618/p < 0.001) retained independently higher risks than those with LSPS <1.1. CONCLUSION: LSM and LSPS are useful in risk assessment of hepatic decompensation among complication-naive B-viral cirrhotic patients.

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 ß-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.

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.

Non-invasive assessment of changes in liver fibrosis via liver stiffness measurement in patients with chronic hepatitis B: impact of antiviral treatment on fibrosis regression.

BACKGROUND: Liver stiffness measurement (LSM) can assess liver fibrosis in patients with chronic hepatitis B (CHB). We evaluated whether LSM can be used to assess changes in liver fibrosis during antiviral treatment using nucleos(t)ide analogs in patients with CHB. METHODS: We recruited 41 patients with CHB who had significant liver fibrosis, normal or slightly elevated serum alanine aminotransferase (ALT) levels (≤2 × upper limit of normal), and detectable serum hepatitis B virus DNA before antiviral treatment. Patients in Group 1 (n = 23) and Group 2 (n = 18) underwent follow-up LSM after antiviral treatment for 1 and 2 years, respectively. RESULTS: The mean age, ALT and LSM value of all patients (34 men and 7 women) before antiviral treatment were 46.6 ± 9.5 years, 40.6 ± 17.2 IU/L and 12.9 ± 8.6 kPa, respectively. Hepatitis B e antigen (HBeAg) was detected in 31 patients (75.6%). Fibrosis stage was F2 in 12 (29.3%), F3 in 6 (14.6%) and F4 in 23 (56.1%) patients. After antiviral treatment, LSM values and DNA positivity decreased significantly as compared to baseline (P = 0.018 and P < 0.001 in Group 1; P = 0.017 and P < 0.001 in Group 2, respectively), whereas ALT levels were unchanged (P = 0.063 in Group 1; P = 0.082 in Group 2). CONCLUSIONS: Our preliminary data suggest that LSM can be used to assess liver fibrosis regression after antiviral treatment using nucleos(t)ide analogs in patients with CHB.

External validation of P2/MS and comparison with other simple non-invasive indices for predicting liver fibrosis in HBV-infected patients.

BACKGROUND: To optimize management strategies and predict the long-term clinical course in patients with chronic hepatitis B (CHB), non-invasive tests to determine the degree of hepatic fibrosis have been developed. AIMS: We aimed to conduct a large-scale external validation of a simple, non-invasive test called P2/MS using CHB patients and to compare it to other non-invasive tests for the prediction of histological cirrhosis. METHODS: From 2006 to 2009, we enrolled a total of 521 consecutive CHB patients who underwent liver biopsy. Fibrosis stage was assessed according to the Metavir scoring system by a single pathologist who was unaware of the patients' histories. RESULTS: For predictions of significant (p>or=2) and severe (p>or=3) fibrosis and cirrhosis (p=4), the areas under the receiver operating characteristic curves were 0.801, 0.856, and 0.906, respectively. In predicting cirrhosis, we found that diagnostic values were comparable to age-spleen platelet ratio index (0.931, p=0.063), spleen-platelet ratio index (0.923, p=0.145), age-platelet index (0.914, p=0.670), and FIB-4 (0.898. p=0.597) and had better outcomes than the aspartate aminotransferase (AST)-platelet ratio index (0.780, p<0.001), and AST-alanine aminotransferase ratio index (0.729, p<0.001). The cut-off points of P2/MS>83 and P2/MS<30 provided 91.1% of negative predictive value and 91.3% of positive predictive value, respectively. Based on these results, liver biopsies could be avoided in 67.0% of the population. These cut-offs were validated internally using bootstrap resampling methods, which showed good agreement. CONCLUSIONS: P2/MS is a simple, accurate, and inexpensive method with comparable outcomes to other non-invasive tests and may reduce the need for liver biopsy in the majority of CHB patients.