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Background: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used 18F-2-fluoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC. Materials and methods: A total of 29 patients with HCC were included. Baseline 18F-FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient. Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0-12.0] and 3.8 months (95% CI: 1.4-6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α-fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors ( P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too ( P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax ( n=10; <5.00) and high SUVmax ( n=19;≥5.00), the low SUV group showed significantly longer OS and PFS ( P=0.023 and P=0.042 respectively). Conclusion: Our study showed that the degree of FDG uptake is an independent prognostic factor in patients with HCC who undergo sorafenib treatment. [ABSTRACT FROM AUTHOR]

The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. We estimated that 49.3-64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is associated with chronic progressive liver disease. Its global epidemiology is still not well ascertained and its impact will be confronted with a higher burden in the next decade. The goal of this study was to develop a tool that can be used to predict the future prevalence of the disease in different countries and, more importantly, to understand the cause and effect relationship between the key assumptions and future trends. A system approach was used to build a simulation model where each population was modeled with the appropriate inflows and outflows. Sensitivity analysis was used to identify the key drivers of future prevalence. The total HCV-infected population in the US was estimated to decline 24% from 3.15 million in 2005 to 2.47 million in 2021, while disease burden will increase as the remaining infected population ages. During the same period, the mortality rate was forecasted to increase from 2.1 to 3.1%. The diagnosed population was 50% of the total infections, while less than 2% of the total infections were treated. We have created a framework to evaluate the HCV-infected populations in countries around the world. This model may help assess the impact of policies to meet the challenges predicted by the evolution of HCV infection and disease. This prediction tool may help to target new public health strategies. [ABSTRACT FROM AUTHOR]

We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea. Between June 2005 and July 2009, 91 CHC patients without a previous history of antiviral treatment, clinical evidences of cirrhosis, coinfection with other viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT) ≤ 5x upper limit of normal, total bilirubin ≤ 1.5 mg/dL, sufficient liver biopsy quality (≥ 15 mm and more than six portal tracts), interquartile range to median liver stiffness (LS) value ratio ≤ 0.21, and more than 10 valid measurements, were recruited. The Batts and Ludwig scoring system was used for histologic assessment. Age-platelet index (API), aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and age-spleen-platelet ratio index (ASPRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of LSM and other noninvasive models. The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47 women). LS value was highly correlated to the fibrosis stages ( r = 0.835, P < 0.001). The AUROCs of LSM were 0.909 for ≥ F2, 0.993 for ≥ F3, and 0.970 for F = 4 and were superior to those of API (0.72, 0.858, and 0.948, respectively), APRI (0.780, 0.887, and 0.904, respectively), and ASPRI (0.713, 0.862, and 0.957, respectively). The optimal cutoff LS values were 6.2 kPa for ≥ F2, 7.7 kPa for ≥ F3, and 11.0 kPa for F = 4. Our data suggest that LSM can accurately assess liver fibrosis in patients with CHC and be applied in South Korea. [ABSTRACT FROM AUTHOR]

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents. [ABSTRACT FROM AUTHOR]

Backgrounds/aims: 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. Methods: 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 χ2-test/ t-test and logistic regression respectively. Thereafter, a prediction model was derived from multivariate predictors. Results: 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 × spleen diameter/platelet count) × 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 ALT≤upper limit of normal (ULN) (normal-ALT group, 164 patients) and ALT>ULN (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. Conclusions: LSPI is a useful, non-invasive tool that can replace liver biopsy in the assessment of liver fibrosis in the majority of CHB patients. [ABSTRACT FROM AUTHOR]

Backgrounds: 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. Aims: 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 (%) × segmented neutrophil fraction (%)], and compared it with other predictive tests for HOVs in B-viral cirrhotic patients. Methods: From 2008 to 2009, we prospectively enrolled 318 consecutive B-viral cirrhotic patients. All underwent endoscopy and laboratory evaluation. Results: 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, P<0.001), aspartate aminotransferase (AST)–platelet ratio index (0.871, P<0.006) and AST-alanine aminotransferase ratio (0.644, P<0.001). P2/MS<11 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. Conclusions: P2/MS is a simple, accurate and economical method, reducing the need for endoscopy in B-viral cirrhosis. Patients with P2/MS<11 should be considered for appropriate prophylactic treatments, while those with P2/MS>25 may avoid endoscopy reliably. [ABSTRACT FROM AUTHOR]

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. Aims: This study aimed to validate a simple, noninvasive FIB-4 index, which was first derived from an HCV–HIV-co-infected population, in patients with CHB and to compare it with other noninvasive tests for predicting cirrhosis. Methods: From 2006–2008, a total of 668 consecutive CHB patients who underwent liver biopsies were enrolled. The fibrosis stage was assessed according to the Batts and Ludwig system by a single pathologist blinded to patients' data. Results: For prediction of significant ( F≥2) and severe ( F≥3) fibrosis, and cirrhosis ( F=4), the area under the receiver-operating characteristic curves were 0.865, 0.910 and 0.926 respectively. In predicting cirrhosis, it demonstrated diagnostic values comparable to the age–spleen platelet ratio index (0.937, P=0.414) and age–platelet index (0.928, P=0.888), and better outcomes than spleen–platelet ratio index (0.882, P=0.007), aspartate aminotransferase (AST)–platelet ratio index (0.731, P<0.001) and AST–alanine aminotransferase ratio index (0.730, P<0.001). FIB-4 cut-offs of 1.6 and 3.6 provided 93.2% negative predictive value and 90.8% positive predictive value for detection of cirrhosis respectively. Based on these results, liver biopsy could be avoided in 70.5% of the study population. These cut-offs were validated internally using bootstrap resampling methods, showing good agreement. Conclusions: FIB-4 is a simple, accurate and inexpensive method of predicting cirrhosis, with outcomes comparable to other noninvasive tests and may reduce the need for liver biopsy in the majority of CHB patients. [ABSTRACT FROM AUTHOR]

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 <5% of the hepatocytes. The mean age of our study population was 38.9 ± 11.9 years (35 men and 34 women), with a mean LS value of 4.6 ± 0.5 kPa (range 3.3–5.6 kPa). LS values were not significantly different between men (4.6 ± 0.6 kPa) and women (4.5 ± 0.5 kPa, P=0.636), nor were they significantly different according to age ( P=0.851). Using the fifth and 95th percentiles, we determined the normal range of LS values to be 3.9–5.3 kPa. Conclusions: We identified the normal range of LS values and found that LS values were not significantly influenced by age and gender. [ABSTRACT FROM AUTHOR]

Background and Aim: Ascitic fluid infection (AFI) consists of culture-negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)-related cirrhotic patients. Methods: We analyzed 130 consecutive patients hospitalized due to the first episode of AFI between January 1998 and December 2007. Results: The mean age of the patients was 52.3 years (88 men, 42 women). Ninety-three patients (71.5%) had CNNA and 37 patients (28.5%) had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months. Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4 months, respectively ( P = 0.417). Patients with SBP showed higher in-hospital mortality than those with CNNA (16.2 vs 4.3%; P = 0.031). Binary logistic regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP) was the only independent predictor of in-hospital mortality ( P = 0.042). In a Cox regression model for the 120 patients (92.3%) who survived the first episode of AFI, only the Child–Pugh score remained significant for survival ( P = 0.007), whereas no association was observed for culture positivity of ascitic fluid (CNNA vs SBP) during the first episode of AFI ( P = 0.752). Conclusions: Although in-hospital mortality was higher in patients with SBP than CNNA, the clinical course of the two groups was similar after the first episode of AFI. Thus, liver transplantation should be considered, irrespective of culture positivity of ascitic fluid. [ABSTRACT FROM AUTHOR]

Ascites is the most common complication of liver cirrhosis, and it develops as a consequence of portal hypertension and splanchnic vasodilatation. Depending on severity, management of ascites consists of diverse strategy, including dietary sodium restriction, diuretic therapy, repeated large-volume paracentesis with albumin infusion, transjugular intrahepatic portosystemic shunt, and liver transplantation. Recently, advances in medical therapy have been made with satavaptan, a V2 receptor antagonist, vasoconstrictors, such as clonidine, midodrine, or terlipressin, and other categories of drugs, including docarpamine and Chinese herbs. These drugs may serve as useful adjuncts to conventional diuretics in the management of ascites. Besides ascites itself, serious complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome, frequently ensue in decompensated cirrhosis. SBP develops from the translocation of bacteria from the intestine, and successful management with early diagnosis and treatment with proper prevention in patients of high risk is necessary. In summary, ascites is a starting point for more serious complications in liver cirrhosis. Although liver transplantation is the fundamental treatment, it is not always feasible, and consequently various means of treatment should be used. Further study, particularly in Asia where hepatitis B virus-related cirrhosis is predominant, is warranted to improve the clinical outcome. [ABSTRACT FROM AUTHOR]

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<0.001), total bilirubin ( P=0.004) and prothrombin time ( P=0.005). However, additional correlation analysis between the changes in LSM value and biochemical factors from diagnosis to recovery showed that the change in total bilirubin was found to be the only factor associated with the change in the LSM value ( P<0.001). Conclusions: Our data suggest that the LSM value might be influenced by serum total bilirubin in patients with acute hepatitis without pre-existing underlying chronic liver disease. [ABSTRACT FROM AUTHOR]

Aim: To investigate the variability in liver stiffness measurement (LSM) values from the fifth, sixth and seventh intercostal space (ICS) and examine whether LSM better predicts significant fibrosis (F2–4) and cirrhosis when LSM is performed at the same site as liver biopsy (LB). Methods: This study enrolled 91 consecutive patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) who underwent both LB and LSM between September 2007 and January 2009. Results: The mean age of the patients was 45.4 years (66 men and 25 women). F1 fibrosis was noted in 12 patients (13.2%), F2 in 28 (30.7%), F3 in 15 (16.5%) and F4 in 36 (39.6%). The mean LSM values from the fifth, sixth and seventh ICS were 11.6, 11.1 and 10.9 kPa respectively. The mean LSM value from the same site as LB was 11.0 kPa. An interclass correlation analysis showed no significant difference in LSM values from the fifth, sixth and seventh ICS and the same site as LB. The area under the receiver operating characteristic curves of LSM values from the fifth, sixth and seventh ICS and the same site as LB for predicting significant fibrosis were 0.815, 0.838, 0.818 and 0.837, respectively, and those for cirrhosis were 0.919, 0.916, 0.907 and 0.913, respectively, with all overlapping confidence intervals. Conclusions: Any LSM value from the fifth, sixth or seventh ICS can predict significant fibrosis and cirrhosis with considerable accuracy without statistical differences regardless of correspondence with LB site in patients with HBV-related CLD. [ABSTRACT FROM AUTHOR]

Background and Aim: Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified. Methods: A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence. Results: The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence. Conclusions: The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated. [ABSTRACT FROM AUTHOR]

Background and Aim: Few studies have assessed the natural history of hepatitis B virus (HBV)–related cirrhotic ascites. We investigated the natural history of patients with HBV-related cirrhotic ascites hospitalized to control ascites and determined their prognosis, including survival rates and prognostic factors affecting survival. Methods: Between January 1996 and December 2005, 203 consecutive patients with HBV-related cirrhotic ascites were followed for a median of 80.7 months (range, 15–149) after their first significant ascitic decompensation that required hospitalization. Results: The mean age of all patients was 52.6 years. Male gender predominated (male/female, 138/65). A subgroup analysis of 165 patients who had ascitic decompensation as their first episode of hepatic decompensation revealed that gastrointestinal variceal bleeding developed after a median interval of 8 months following ascitic decompensation in 31 (18.8%) patients, hepatic encephalopathy occurred at 9 months in 53 (32.1%), spontaneous bacterial peritonitis appeared at 12.7 months in 24 (14.5%), hepatorenal syndrome occurred at 8.1 months in five (3%), and hepatocellular carcinoma was observed at 21.2 months in 10 (6.1%). The overall median survival was 12.4 months. The 1- and 3-year survival rates were 50.7 and 18.7%. The prognostic factors that independently correlated with survival at the time of ascitic decompensation were Child–Pugh classification B/C ( P = 0.030), serum white blood cell (WBC; P = 0.035), serum creatinine (Cr; P = 0.039), serum sodium (Na; P = 0.010), and antiviral therapy ( P = 0.040). Conclusions: The prognosis of HBV-related cirrhotic patients with ascitic decompensation is poor. Child–Pugh class, serum WBC/Cr/Na, and antiviral therapy primarily influenced survival. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatitis C virus (HCV) is one of the major causes of liver cirrhosis and hepatocellular carcinoma (HCC) in Mongolia. However, there are no data concerning nationwide prevalence of HCV infection in Mongolia. We intended to investigate the population-based prevalence of HCV infection and genotype distribution among 1512 apparently healthy individuals in this country. Methods: Between April 2003 and December 2005, sera from 1512 residents of Ulaanbaatar and 12 provinces were collected by two-stage cluster random sampling, and anti-HCV was tested. Anti-HCV-positive samples were tested for HCV RNA by reverse transcription polymerase chain reaction, and HCV genotype was determined. Results: The mean age of the subjects was 46.2±17.8 years, and 812 (53.7%) were male. Overall, the prevalence of anti-HCV was 15.6% (236/1512) and HCV RNA was detected in 167 subjects (11.0%), with the most common genotype being 1b (165/167, 98.8%). When the HCV RNA-positive subjects were categorized by decade of age, the prevalence in each age group was as follows: 2.5% in subjects ≤10 years of age, 4.5% in teens, 10.1% in 20's, 12.5% in 30's, 24.2% in 40's, 29.0% in 50's and 32.6% in subjects ≥61 years of age. The seroprevalence of anti-HCV in a risk group, nurses, was not significantly different from the general population in each decade of age ( P>0.05). Conclusions: Approximately 11.0% of apparently healthy population had detectable HCV RNA in Mongolia, and the predominant genotype of HCV was 1b. Preventive and therapeutic strategies for chronic hepatitis C are urgently warranted in this HCV-endemic area. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have a particularly grave prognosis. In the current study, an attempt was made to localize chemoradiation therapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in patients with locally advanced HCC with PVT and good reserve liver function. The objective of the current study was to evaluate the therapeutic effect of localized CCRT followed by HAIC as a new treatment modality for these patients.Methods: Between January 1998 and December 2003, 40 patients were recruited. Concurrent regional chemotherapy using an intra-arterial implanted port plus localized external beam radiotherapy was performed with a total of 45 gray (Gy) over 5 weeks with conventional fractionation and hepatic arterial infusion of 5-fluorouracil (5-FU), which was administered during the first and fifth weeks of radiotherapy. One month after localized CCRT, HAIC with 5-FU and cisplatin was administered every 4 weeks.Results: One month after localized CCRT, an objective response was observed on the intention-to-treat analysis in 18 of 40 patients (45%). The actuarial 3-year overall survival rate was 24.1% and the median survival time was 13.1 months from the start of radiation treatment. Responders after localized CCRT demonstrated significantly better survival (P = .033) than nonresponders.Conclusions: The substantial response rate as well as median survival time noted in the current study encourages the use of this new approach in patients with locally advanced HCC with PVT. [ABSTRACT FROM AUTHOR]

Background and Aim: Monotherapy of lamivudine, interferon-alpha (IFN-α), and thymosin alpha-1 (Tα1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of Tα1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. Methods: Sixty-seven patients were assigned to two different groups in a randomized manner. The combination group ( n = 34) received Tα1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group ( n = 33) received lamivudine monotherapy continuously. Results: The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group ( P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks ( P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks ( P = 0.201). Conclusions: The combination treatment of Tα1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of Tα1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs. [ABSTRACT FROM AUTHOR]

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. Patients and methods: 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, α-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. Results: 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. Conclusions: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly malignant cancer and third major cause of death in Korean. It is more prevalent among men in the sixth to seventh decades. HCC is particularly prevalent in Korea where the age-standardized incidence rate is 45.0/100 000 population in males and 12.0/100 000 population in females. The death rate from HCC is 20.0/100 000 population. Approximately 65–75% of HCC patients were positive for hepatitis B surface antigen (HBsAg), where 10–20% of patients were anti-hepatitis C virus (HCV) positive. The high incidence rate of HCC in Korea is thought to be related to the high carrier rate of hepatitis B virus (HBV) in the general population. For primary prevention, a nationwide HBV vaccination program has been conducted since the late1980s in Korea. Although advances have been made in the various methods of management of HCC, there has been little overall survival improvement during the past 20 years. Only few patients are candidates for potentially curative forms of treatment. Therefore, the early detection of HCC is a key issue. When compared with clinical outcomes of HCC based on recent 10-year institutional data, our screening and surveillance programs might enable early detection and increased applicability of curative treatments. [ABSTRACT FROM AUTHOR]

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. Patients and methods: 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. Results: AAR, APRI, SPRI, API, and ASPRI correlated significantly to fibrosis stage (all P<0.001). 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 ASPRI>12, 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 of <5, the presence of cirrhosis could be totally excluded with 100% of negative predictive value in 120 (34.7%) of 346 patients. Conclusion: ASPRI was accurate in predicting cirrhosis and screening with ASPRI has the potential to reduce the number of liver biopsies in CHB patients. [ABSTRACT FROM AUTHOR]

The article discusses a study on the efficacy and safety of repetitive short-course hepatic arterial infusion chemotherapy (HAIC) with high-dose 5-fluorouracil (5-FU) and cisplatin in patients with advanced hepatocellular carcinoma (HCC). Results indicate that of the 41 subjects, nine patients exhibited partial response while 14 had stable disease. It adds that adverse reactions from the treatment are tolerable. It concludes that the therapy can serve as an alternative therapy for patients with advanced HCC.

Background and Aim: This study evaluated the long-term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage. Methods: A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re-evaluated based on histological grade and stage. Results: During follow-up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto-periportal activity. The development of cirrhosis correlated well with the grade of porto-periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared-up without normalization than in patients whose ALT levels flared-up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow-up were independent prognostic factors for chronic hepatitis B. Conclusions: The results demonstrate that histological grade and stage, and biochemical profile during follow-up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long-term outcome of chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

In order to determine the effect of additional radiotherapy (RT) after an incomplete transcatheter arterial chemoembolization (TACE) in an unresectable hepatocellular carcinoma (HCC), the treatment results of patients receiving TACE plus RT were analyzed and compared with those treated with TACE alone. Materials and methods: One hundred and five patients with an unresectable HCC were treated with TACE from January 1992 to December 2002. In 73 of these patients, the TACE was incomplete. Among them, TACE was repeatedly performed in 35 patients (TACE group), and the remaining 38 patients were also treated with local RT (TACERT group). The patients were either in stage III or IVa, Eastern Cooperative Oncology Group 2 or less, and Child–Pugh class A or B. The average frequency of TACE prior to RT was 2 and the RT was started within 7–10 days after the TACE. Results: The 2-year survival rate was significantly higher in the TACERT than in the TACE group (36.8 % vs. 14.3%, P=0.001). According to the tumor size, the 2-year survival rates in the TACERT and TACE groups were 63% vs. 42% in 5–7 cm ( P=0.22), 50% vs. 0% in 8–10 cm ( P=0.03), and 17% vs. 0% in larger than 10 cm ( P=0.0002) respectively. Conclusion: There was a significantly improved survival rate in the TACERT group of unresectable HCC patients than in the TACE group, particularly in case of tumors ≥8 cm in diameter. Therefore, RT in addition to TACE is strongly recommended for patients with an unresectable HCC. [ABSTRACT FROM AUTHOR]

Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. Methods: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count ≥250/mm3. Results: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. Conclusion: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites. [ABSTRACT FROM AUTHOR]

Large volume paracentesis (LVP) with plasma volume expansion has been used for tense or refractory ascites. However, still in question is whether it is safe and effective for the treatment of spontaneous bacterial peritonitis (SBP). We addressed this issue and conducted a study to assess safety and long-term outcome of LVP in cirrhotic patients with SBP. Forty-two randomly assigned cirrhotic patients with SBP were classified into two groups; Group 1 included 21 patients who were treated with LVP and intravenous albumin; and Group 2 included 21 patients who were treated with diuretics and intravenous albumin. The overall cumulative survival rate was poor in patients with SBP (42.5% and 22.5% at 6 and 12 months, respectively). At 7 days after treatment, the blood tests were similar between the two groups. In the ascitic fluid, the white blood cell counts decreased significantly and the protein concentrations tended to increase in both groups. In-hospital days, resolution rate of SBP, and in-hospital mortality rate were similar between the two groups. Although complication rates tended to be slightly higher in Group 1, long-term cumulative survivals were similar between Group 1 and Group 2. LVP was effective in removing abdominal discomfort in patients with tense ascites without serious complication. LVP with intravenous albumin was as effective as diuretics with intravenous albumin for the treatment of SBP with similar mortality. LVP with intravenous albumin might be feasible for the treatment of tense or refractory ascites in cirrhotic patients with SBP. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection has been known to be hampered by immunity against hepatitis B surface antigen (HBsAg). However, HBV with mutations within the common antigenic epitope of HBsAg, the ‘a’ determinant region, can escape from humoral immunity. Moreover, HBV infection by ‘a’ determinant mutants in chronic HBV patients has been reported after renal transplantation. In the present study, the authors investigated HBV infection after renal transplantation despite passive immunization or resolved HBV infection. A total of 1682 patients who underwent a renal transplant between 1979 and 1998 at the Severance Hospital, Yonsei University College of Medicine, Korea, were enrolled. The sequence of the HBV genome was analyzed from two patients with antibody to HBsAg (anti-HBs) immunity. Of 1682 patients who were HBsAg negative before transplantation, 21 patients were found to be HBsAg positive, with elevated aspartate aminotransferase and alanine aminotransferase levels after transplantation. Interestingly, six of 21 (28.6%) patients were anti-HBs positive before the transplantation. Sequence analysis of the cloned HBV from two of six patients with anti-HBs immunity showed no evidence of significant mutations within the ‘a’ determinant region, suggesting a wild-type of HBV. Their donors were not exposed to HBV before transplantation (all HBV markers were negative). Seven deaths of 21 patients were ascribed to HBV-related complications. Regardless of anti-HBs immunity, HBV infection occurred in immunosuppressed patients in a high endemic area. The molecular mechanism and clinical impact of HBV infection after renal transplantation in patients with anti-HBs immunity should be further reappraised. © 2004 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

Discusses treatment options for non-resectable hepatocellular carcinoma (HCC). Overview of HCC therapies; Non-surgical treatment of HCC; Transcatheter arterial chemoembolization; Radiation therapy; Percutaneous ethanol injection.

Provides an overview of immunogenetic studies of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) studies; Relationship between tumor necrosis factor-alpha promoter polymorphism and the clearance or persistence of HBV.

The authors reflect on the assessment of liver fibrosis using non-invasive procedure. They examine the proposed formula for fibrosis prediction named HALF index on the study by H. J. Lee and colleagues. They mention several issues that must be considered in cross-sectional studies concerning noninvasive fibrosis prediction models, which include the discrepancy in interpreting liver biopsy (LB) and the models, the limitation in validating serologic fibrosis markers and formulae, and cost issue.

See article in J. Gastroenterol. Hepatol. 2010; 25: 1117–1122 [ABSTRACT FROM AUTHOR]

The author examines hepatocellular carcinoma (HCC) and the means to treat the disease. He claims that HCC is the third most common cause of cancer-related death worldwide, and with no treatment so far because of its acquired resistance to chemotherapeutic agents. To treat the disease, hepatic arterial infusion chemotherapy was introduced. He explains that the process is done by administering chemotherapeutic agents into the hepatic artery, thereby exposing the tumor cells to levels of the drug.

The authors reflect on several studies that proposed replacement methods for liver biopsy, which had been used to assess liver fibrosis. They cite the study of R. Malik and colleagues which suggested the transient elastography (TE) that can be used for assessing liver fibrosis and predicting cirrhosis in patients with chronic liver disease. Meanwhile, the cohort study of Kun and colleagues confirmed the accuracy of S-index in diagnosing fibrosis in patients with chronic hepatitis B (CHB).