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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. more...

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 ( 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 more...

While liver stiffness measurement (LSM) predicts histological cirrhosis accurately, complementary methods are needed for better performance. Furthermore, alanine aminotransferase (ALT) influences LSM, making it necessary to modify its use in patients with high ALT levels. We developed a new LSM-based prediction model for cirrhosis and estimated the thresholds for different ALT levels.From 2008 to 2009, we prospectively enrolled 330 consecutive patients who were diagnosed with chronic hepatitis B (CHB) and underwent a liver biopsy and LSM on the same day. For detection of cirrhosis, we performed univariate and multivariate analyses, using the chi(2)-test/t-test and logistic regression respectively. Thereafter, a prediction model was derived from multivariate predictors.In multivariate analyses of patients with and without cirrhosis, we found significant differences in the LSM, spleen diameter and platelet count. Then, we developed an LSM-spleen diameter to platelet ratio index (LSPI): (LSM x spleen diameter/platelet count) x 100. The area under the receiver operating curve was 0.956, significantly higher than LSM alone (0.919, P=0.032). We suggested different thresholds in patients with ALTor = upper limit of normal (ULN) (normal-ALT group, 164 patients) and ALTULN (high-ALT group, 166 patients). In the normal-ALT group, LSPI thresholds of 38 and 62 provided 95.7% negative predictive value (NPV) and a 95.5% PPV (positive predictive value), while in the high-ALT group, thresholds of 42 and 94 yielded 95.1% NPV and 96.4% PPV respectively. Therefore, liver biopsy could be avoided in 76.7% of the subjects.LSPI is a useful, non-invasive tool that can replace liver biopsy in the assessment of liver fibrosis in the majority of CHB patients. more...

Periodic endoscopic screening for oesophageal varices (OVs) and prophylactic treatment for high-risk OVs (HOVs; medium/large OVs or small OVs plus red sign/decompensation) are currently recommended for all cirrhotic patients. However, if a simple, noninvasive test is available, many low-risk patients may reliably avoid endoscopy.We conducted a large-scale validation study of a simple, noninvasive test called P2/MS based on complete blood counts, (platelet count)(2)/[monocyte fraction (%) x segmented neutrophil fraction (%)], and compared it with other predictive tests for HOVs in B-viral cirrhotic patients.From 2008 to 2009, we prospectively enrolled 318 consecutive B-viral cirrhotic patients. All underwent endoscopy and laboratory evaluation.An area under the receiver operating characteristic curve of P2/MS was 0.941 for HOVs, comparable with those of the age-spleen platelet ratio index (0.922, P=0.317) and spleen-platelet ratio index (0.922, P=0.324), and better than those of age-platelet index (0.653, P0.001), aspartate aminotransferase (AST)-platelet ratio index (0.871, P0.006) and AST-alanine aminotransferase ratio (0.644, P0.001). P2/MS11 reliably identified 83 patients as having HOVs (94.0% positive predictive value), while at a cutoff of 25 and 179 as not having HOVs (94.4% negative predictive value). Overall, P2/MS reliably determined the likelihood of HOVs in 262 patients (82.4%). These cutoffs were validated internally using bootstrap resampling methods, which showed good agreement.P2/MS is a simple, accurate and economical method, reducing the need for endoscopy in B-viral cirrhosis. Patients with P2/MS11 should be considered for appropriate prophylactic treatments, while those with P2/MS25 may avoid endoscopy reliably. more...

Aims: To identify the normal range of liver stiffness (LS) values by recruiting healthy living liver and kidney donors in South Korea. Methods: Liver stiffness measurement (LSM) was performed in 69 healthy living liver and kidney donors who were admitted for transplantation. None of the subjects suffered from diabetes mellitus, hypertension, hepatitis B virus infection, hepatitis C virus infection, heart dysfunction, liver dysfunction or metabolic syndrome. Results: LSM failure rate was 2.7%. Among 12 liver donors (17.4%) with available liver histology, eight showed normal liver histology and four showed liver steatosis of more...

Background: Liver stiffness measurement (LSM) using FibroScan® is accepted as a highly reproducible and accurate technique for assessment of liver fibrosis. However, several studies have indicated that the LSM value can be significantly influenced by major changes in aminotransferases in patients with chronic viral hepatitis and LSM is unreliable for diagnosing underlying liver cirrhosis in patients with acute liver damage. We aimed to determine biochemical factors influencing the LSM value in patients with acute hepatitis. Methods: From July to December 2007, a total of 60 patients with acute hepatitis of varying aetiologies were recruited prospectively. LSM and biochemical tests were performed at diagnosis and recovery from acute hepatitis. Results: The mean age of the patients (38 men and 22 women) was 40.7±15.4 years. The aetiology of acute hepatitis included hepatitis A virus in 31 patients, drug induced in 19 and hepatitis B virus in 10. The mean LSM value was 19.6 kPa at diagnosis and 15.9 kPa at recovery. Correlation analysis showed that the LSM value at diagnosis was significantly associated with platelet count (P=0.023), alanine aminotransferase (P=0.045), albumin (P more...

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.We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100,000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (100,000 copies/ml), while 68 (viraemia group) had consistently positive DNA (100 000copies/ml). Serum DNA level, biochemical tests, alpha-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery.There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently.Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA. more...

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.A total of 346 consecutive treatment-naïve patients with CHB were retrospectively studied. The aspartate to alanine aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), SPRI, and ASPRI were compared with liver histology.AAR, APRI, SPRI, API, and ASPRI correlated significantly to fibrosis stage (all P0.001). The diagnostic accuracy of ASPRI was the highest among five tests for prediction of cirrhosis (area under receiver operating characteristic curve, AUROC=0.893). Using a cutoff score of ASPRI12, the presence of cirrhosis could be correctly identified with a high accuracy (96.3% positive predictive value) in 35 (10.1%) of 346 patients. Similarly, using a cutoff of5, the presence of cirrhosis could be totally excluded with 100% of negative predictive value in 120 (34.7%) of 346 patients.ASPRI was accurate in predicting cirrhosis and screening with ASPRI has the potential to reduce the number of liver biopsies in CHB patients. more...