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.

Clinical usefulness of double biomarkers AFP and PIVKA-II for subdividing prognostic groups in locally advanced hepatocellular carcinoma.

BACKGROUND & AIMS: In this study, we investigated the clinical usefulness of AFP and PIVKA-II in subdividing prognostic groups in patients with locally advanced HCC treated locally. METHODS: Patients who had undergone local treatment for locally advanced HCC between 2001 and 2006 were enrolled. Response to treatment was defined as a reduction in AFP or PIVKA-II by more than 50% from baseline levels at 1 month after the treatment completion. Patients were divided according to their AFP and PIVKA-II response: A↓P↓ [AFP response (+) and PIVKA-II response (+)]; A↓P↑ [AFP response (+) and PIVKA-II response (-)]; A↑P↓ [AFP response (-) and PIVKA-II response (+)]; A↑P↑ [AFP response (-) and PIVKA-II response (-)]. Clinical characteristics and prognosis were compared between groups. RESULTS: Patients were subdivided into four groups by the change in the level of the biomarkers AFP and PIVKA-II, and the survival outcomes of each group were distinct. Among patients with an AFP response, further subdivision by PIVKA-II response revealed that those in the A↓P↓ group had a longer median progression-free survival (PFS) and overall survival (OS) compared with those in the A↓P↑ group (PFS: 16.2 vs. 5.1 months, P = 0.009; OS: 26.3 vs. 7.3 months, P = 0.017). Combination of AFP and PIVKA-II response showed a predictive power for PFS and OS comparable to radiological criteria and better than AFP response alone. CONCLUSIONS: In patients with locally advanced HCC, the use of a combination of two biomarkers, AFP and PIVKA-II, appears useful in predicting treatment outcomes through the subdivision of prognostic groups.

Maintaining remission in lamivudine-resistant patients with a virological response to adefovir add-on lamivudine after stopping lamivudine therapy.

BACKGROUND & AIMS: We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD-resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy. METHODS: This study enrolled 72 patients with undetectable viral loads (≤12 IU/ml) and normal alanine aminotransferase levels after ADV add-on therapy for at least 6 months in LVD-resistant CHB patients. The enrolled patients were randomly assigned to continue with LVD-ADV combination therapy or switch to ADV monotherapy (n = 36 per group). Virological rebound was defined as HBV DNA detection at more than 12 IU/ml by quantitative polymerase chain reaction determined on two consecutive measurements. RESULTS: During 96 weeks of follow-up, 100% (36/36) of the patients in the LVD-ADV combination maintained group had persistently undetectable HBV DNA, compared with 94.4% (34/36) patients in the ADV monotherapy switched group. These two patients had undetectable HBV DNA after switching back to LVD-ADV combination therapy. There were no significant differences in the HBsAg levels between the two treatment groups during the 96-week follow-up period. CONCLUSIONS: In our study, switching to ADV monotherapy resulted in sustained HBV DNA suppression in 94.4% of the patients for 96 weeks. Prior complete viral suppression with LVD-ADV combination therapy conferred a significant advantage in patients who switched to ADV monotherapy. LVD may be discontinued in patients who show a complete virological response to LVD-ADV combination therapy for at least 6 months.

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.

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.

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.

Prognostic value of α-fetoprotein and des-γ-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUND/AIMS: Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) have been used as diagnostic tools for hepatocellular carcinoma (HCC). However, prediction of outcome using AFP and DCP has not been elucidated. We investigated the clinical role of AFP and DCP as predictors of treatment outcome in patients with HCC undergoing trans-arterial chemoembolization (TACE). METHODS: Between January 2003 and December 2005, we enrolled 115 treatment-naïve patients who received TACE as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 50% from the baseline level 1 month after TACE. Patients with AFP < 20 ng/mL or DCP < 20 mAU/mL were excluded. RESULTS: The median age was 59 years and the male gender predominated (n = 81, 70.4%). AFP and DCP response was identified in 91 (79.1%) and 77 (66.9%) patients after TACE. Although progression-free survival (PFS) did not differ according to AFP response (P = 0.150), AFP responders showed significantly better overall survival (OS) than non-responders (34.9 vs. 13.2 months; P = 0.002). In contrast, DCP response did not influence either PFS or OS (all P > 0.05). Multivariate analyses showed that gamma-glutamyltranspeptidase and baseline AFP were predictors of PFS (all P < 0.05) and that male gender, the presence of liver cirrhosis, baseline DCP, number of measurable tumors and AFP response were independent predictors of OS (all P < 0.05). CONCLUSIONS: AFP response and higher baseline DCP level are significant predictors of OS in treatment-naïve patients with HCC receiving TACE who showed pretreatment elevation of both AFP and DCP.

Normal enhanced liver fibrosis (ELF) values in apparently healthy subjects undergoing a health check-up and in living liver donors in South Korea.

BACKGROUND: The enhanced liver fibrosis (ELF) value is a non-invasive serum marker used for assessing liver fibrosis in chronic liver disease. To use the ELF value for the purpose of screening the general population and selecting subpopulations at high risk, it is important to know the normal range of ELF values as a prerequisite. AIMS: We aimed to define the normal range of ELF values by recruiting apparently healthy subjects and investigating factors influencing ELF values in subjects with minimal fibrotic burden. METHODS: ELF values were determined in a cohort of healthy subjects who underwent a health check-up and in healthy living liver donors who were screened for transplantation. None of subjects suffered from chronic heart disease, diabetes mellitus, metabolic syndrome, hepatitis B, hepatitis C, or human immunodeficiency virus infection, systemic autoimmune disease or liver dysfunction. RESULTS: Among 183 subjects analyzed, the normal ELF 5th through 95th percentile range was 5.95-8.73. Body mass index (P = 0.014) and male gender (P = 0.015) showed significant positive correlations with ELF value, whereas age did not. In multivariate linear regression analysis, platelet count was identified as the only independent factor influencing the ELF value (ß=-0.006, P = 0.016). When considering the difference in ELF values between genders, the normal range of men was defined to be 6.72-8.93, this was slightly higher than that of women, 5.69-8.67. CONCLUSIONS: We identified the normal range of ELF values and found that it can be significantly influenced by platelet count even in the healthy population.

Survival of hepatocellular carcinoma patients may be improved in surveillance interval not more than 6 months compared with more than 6 months: a 15-year prospective study.

GOALS: To compare hepatocellular carcinoma (HCC) stage, treatment modality, and survival between groups submitted to different surveillance interval. BACKGROUND: It is not clear if surveillance interval affects patient survival with HCC. STUDY: Clinical data from 10,307 patients at risk for HCC were prospectively collected from 1990 to 2005. The characteristics of cancer and 5-year survival in patients diagnosed as HCC during follow-up were compared between surveillance interval of <6 months and beyond 6 months. RESULTS: A total of 400 patients were diagnosed with HCC, with a mean tumor size of 3.5 cm and an annual detection rate of 2.4%. The tumor sizes detected in patients with surveillance interval ≤ 6 months were significantly smaller than those detected in patients with interval of >6 months (n=219; 3.0 ± 1.7 cm vs. n=181; 4.0 ± 2.6 cm, P<0.001). The survival benefit in patients with surveillance interval of ≤ 6 months was significant compared with those with interval of >6 months even after considering lead time with assumed tumor doubling time of 60 days. The 5-year survival of HCC patients surveyed between 2000 and 2004 was significantly higher compared with those surveyed between 1990 and 1994 or between 1995 and 1999 (41% vs. 17% and 19%, respectively, P<0.0001). Using a Cox regression model, Child-Pugh class, Japanese tumor-node-metastasis stage, and α-fetoprotein levels were independently associated with patient survival. CONCLUSIONS: Our data show that surveillance ≤ 6 months might be associated with early detection of HCC and improved survival in a hepatitis B endemic area.

Partial virological response to adefovir add-on lamivudine rescue therapy in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND/AIMS: In patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB) receiving adefovir (ADV) add-on LAM therapy, insufficient viral suppression or the appearance of additional ADV resistance has remained unresolved. This study determined the partial virological response (PVR) criteria to predict a virological response (VR) at week 96 in these patients. METHODS: 96 patients with LAM-resistant CHB (ADV add-on LAM therapy >2 years) were analyzed. For predicting VR at week 96, the area under the receiver operating characteristic curve values at different time points were compared to establish the optimal time point, and the maximal Youden index was calculated to determine the optimal cut-off hepatitis B virus (HBV) DNA level. RESULTS: 50 (52.1%) patients achieved VR at 2 years after ADV add-on LAM therapy. The optimal PVR criteria were determined to be HBV DNA 500 IU/ml at week 48. 44 (45.8%) patients who met optimal PVR criteria showed a significantly higher risk for detectable HBV DNA levels at week 96 than those with a favorable VR (HBV DNA <500 IU/ml) at week 48. CONCLUSIONS: This study suggested optimal PVR criteria in patients with LAM-resistant CHB receiving ADV add-on LAM therapy. Modification of the antiviral agent regimen should be considered if the serum HBV DNA level exceeds 500 IU/ml at week 48.

Early predictor of mortality due to irreversible posthepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Although mortality after liver resection has declined, posthepatectomy liver failure (PHLF) remains a major cause of operative mortality. To date there is not consensus on a definition for PHLF. However, there have been many efforts to define PHLF causing operative mortality. In the present study we sought to identify early predictors of death from irreversible PHLF. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 359 patients with hepatocellular carcinoma who underwent liver resection between March 2000 and December 2010. Various biochemical parameters from postoperative days (POD) 1, 3, 5, and 7 were analyzed and compared with the "50-50" criterion. RESULTS: Operative mortality was 4.7 %. Prothrombin time (PT) <65 % and bilirubin ≥ 38 µmol/L on POD 5 showed the only significant difference as compared with "50-50" criterion. The new combination of bilirubin level and the international normalized ratio showed higher sensitivity, area under the curve, as well as similar accuracy (sensitivity 78.6 vs. 28.6 %; p = 0.002; area under the curve 0.8402 vs. 0.6396; p = 0.00176; accuracy 88.6 vs. 93.4 %; p = 0.090). Multivariate analysis revealed the combination of PT <65 % and bilirubin ≥ 38 µmol/L on POD 5 to be the only independent predictive factor of mortality (odds ratio, 82.29; 95 % confidence interval 8.69-779.64; p < 0.001). CONCLUSIONS: In patients with chronic liver disease who will undergo liver resection the combination of PT <65 % and bilirubin ≥ 38 µmol/L on POD 5 may be a more sensitive predictor than the "50-50" criterion of mortality from PHLF. Although it needs to validated by prospective study, this measure may be applied to select patients receiving artificial liver supports or liver transplantation.

Combined measurement of preoperative α-fetoprotein and des-γ-carboxy prothrombin predicts recurrence after curative resection in patients with hepatitis-B-related hepatocellular carcinoma.

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are widely used complementary tumor markers for hepatocellular carcinoma (HCC). In this study, we investigated whether preoperative AFP and DCP levels predict recurrence after curative resection in patients with hepatitis B virus (HBV)-related HCC. Records for 267 patients who were diagnosed with HBV-related HCC and who underwent curative resection for HCC were retrospectively reviewed. Patients were divided into two preoperative groups: pre-op I (AFP ≥ 20 ng/dL and DCP ≥ 40 mAU/mL) and pre-op II (AFP ≥ 20 ng/dL and DCP <40 mAU/mL; AFP <20 ng/dL and DCP ≥ 40 mAU/mL; or AFP <20 ng/dL and DCP <40 mAU/mL). Among 267 patients, 102 (38.2%) patients were classified as pre-op I, whereas the other 165 (61.8%) belonged to pre-op II. During the post-resection follow-up [69.0 (3.0-136.0) months] period, 154 (57.7%) patients developed recurrences [68 (66.7%) patients in pre-op I vs. 86 (52.1%) in pre-op II, p = 0.029]. A multivariate analysis revealed that multiple tumors [hazard ratio (HR), 2.210; 95% confidence interval (CI), 1.185-4.121] and pre-op I (HR: 1.890; 95% CI; 1.080-3.289) were significant predictors for recurrence. Disease-free survival (DFS) was significantly shorter in pre-op I compared to that in pre-op II (20.0 vs. 46.8 months, p = 0.006). Elevated preoperative AFP and DCP levels were associated with a higher recurrence rate and shorter DFS in patients with HBV-related HCC after curative resection. The combined measurement of preoperative AFP and DCP may be a prognostic factor for future recurrence.

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.

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir.

UNLABELLED: Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(-) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. CONCLUSION: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated.

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.

Predictive value of HBsAg quantification for determining the clinical course of genotype C HBeAg-negative carriers.

BACKGROUND/AIMS: Hepatitis B virus surface antigen (HBsAg) quantification has been suggested to discriminate inactive carriers from hepatitis e antigen (HBeAg) negative chronic hepatitis, but it could be genotype-dependent. We studied the predictive value of HBsAg quantification in genotype C HBeAg-negative hepatitis B virus (HBV) carriers. METHODS: We recruited 104 HBeAg-negative HBV carriers with HBV DNA levels < 2,000 IU/ml and normal alanine aminotransferase (ALT) levels for at least 12 months and prospectively followed them for > 36 months. Patients were classified into two groups: inactive carriers (IC) who showed HBV DNA levels < 2,000 IU/ml and persistently ALT ≤ 40 IU/ml throughout the follow-up period and patients with HBeAg-negative chronic hepatitis (ENH). RESULTS: After follow-up, 73 patients were categorized into the IC group and 31 patients into the ENH group. HBsAg levels were significantly lower in the IC group than in the ENH group. The diagnostic accuracy of single-point HBsAg levels for predicting viral activation was favourable (AUROC = 0.710, P < 0.001). Diagnostic accuracy improved when HBsAg was combined with baseline HBV DNA levels (AUROC = 0.750, P < 0.001). The combination of HBsAg levels > 850 IU/ml and HBV DNA > 850 IU/ml predicted the reactivation of HBV replication with 84.6% diagnostic accuracy. CONCLUSIONS: Although it is inferior to other genotypes and to serum HBV DNA alone, single-point HBsAg level has a favourable diagnostic accuracy in genotype C HBeAg-negative HBV carriers and is expected to provide additional information for managing chronic hepatitis B.

Lamivudine plus adefovir vs. entecavir in HBeAg-positive hepatitis B with sequential treatment failure of lamivudine and adefovir.

BACKGROUND AND AIMS: Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12. METHODS: In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months. RESULTS: Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044). CONCLUSIONS: Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

Optimal time for restoring the reliability of liver stiffness measurement in patients with chronic hepatitis B experiencing acute exacerbation.

BACKGROUND/AIMS: Liver stiffness measurement (LSM) using transient elastography (FibroScan) is influenced by major changes in aminotransferase. We aimed to determine the optimal time for restoring the reliability of LSM for assessing liver fibrosis in patients with chronic hepatitis B experiencing acute exacerbation. METHODS: Twenty-one patients with acute exacerbation of chronic hepatitis B [alanine aminotransferase (ALT)>5× upper limit of normal (ULN)] were prospectively recruited. Serial LSM and biochemical tests were performed at the time of admission and after 1, 3, 6, 9, and 12 months. The ULN of ALT was defined as 40 IU/L. The cutoff LSM value for cirrhosis was defined as 10.3 kPa. RESULTS: The median age (9 male) was 49 years. The median ALT and LSM in the baseline were 522 IU/L and 15.1 kPa, respectively. Three months after acute exacerbation, ALT had decreased significantly below 2× ULN and stabilized (median: 522, 43, 21, 19, 18, and 16 IU/L at baseline, 1, 3, 6, 9, and 12 mo, respectively). However, LSM needed 3 more months (6 mo after exacerbation) for stabilization (median: 15.1, 10.0, 7.4, 7.1, 6.3, and 5.8 kPa at baseline, 1, 3, 6, 9, and 12 mo, respectively). CONCLUSIONS: LSM should be postponed for at least 3 months after stabilization of ALT below 2× ULN to restore the reliability of LSM in assessing liver fibrosis.

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.

Combination of preS deletions and A1762T/G1764A mutations in HBV subgenotype C2 increases the risk of developing HCC.

BACKGROUND: The interactions among hepatitis B virus (HBV) mutations in developing hepatocellular carcinoma (HCC) remain unclear and thus we investigated the risk of HCC related with single or multiple HBV mutations in Korean patients infected with HBV subgenotype C2. METHODS: From January 2003 to December 2008, HBV isolates from 135 patients with HCC were compared with those from 135 patients without HCC, matching for age, gender, and HBeAg status. The prevalence of preS deletions and G1896A and A1762T/G1764A mutations was evaluated. RESULTS: The frequency of preS deletions significantly differed between the non-HCC and HCC groups, with 6 (4.4%) versus 25 (18.5%) patients, respectively (p < 0.001). Additionally, the frequency of A1762T/G1764A mutations was higher in the HCC than the non-HCC group [82 (60.7%) versus 30 (22.2%), p < 0.001]. For combined mutations, the odds ratio (OR) was highest in patients with both preS deletions and the A1762T/G1764A mutation, with 1 (0.7%) versus 11 (8.1%) patients (p = 0.005; OR 11.887). CONCLUSIONS: HCC was associated with preS deletions and A1762T/G1764A mutations, and the combination of both mutations had a stronger association with HCC in Korean patients infected with HBV subgenotype C2.