Yeon k Seo

Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil

Background: Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment naïve chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8–3%, and ∼5.9%, respectively. Aims: The aim of this study was to characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV resistant CHB patients who were treated with ADV. Methods: Serum HBV DNA was quantified by real time polymerase chain reaction. The ADV mutant was detected using matrix assisted laser desorption/ionisation time of flight mass spectrometry based genotyping assays, termed restriction fragment mass polymorphism (RFMP). Results: RFMP analysis revealed that a total of 11 amino acid substitutions developed in the rt domain of the HBV polymerase in nine patients. The cumulative incidence of genotypic ADV resistance at months 12 and 24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations were detected in five, four, and two of the 67 patients at treatment months 12–17, 3–19, and 7–20, respectively. Serial quantification of serum HBV DNA revealed that two patients with the rtA181V mutation, with or without the rtN236T mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound. Conclusion: Emergence of the ADV mutation in LMV resistant patients who are treated with ADV appeared to present earlier and more frequently than was reported in previous studies on nucleoside/-tide treatment naïve patients.

PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes.

Background and Aims:  In a previous study, the authors found that reduced expression of peroxisome proliferator‐activated receptor (PPAR)‐α might play an important role in developing nonalcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the effects of PPAR‐α and ‐γ agonists on NAFLD and verify the mechanisms underlying the PPAR‐α and ‐γ agonist‐induced improvements by evaluating the hepatic gene expression profile involved in fatty‐acid metabolism, using the Otsuka–Long Evans–Tokushima fatty (OLETF) rat.

Comparison of the methods for tumor response assessment in patients with hepatocellular carcinoma undergoing transarterial chemoembolization

BACKGROUND & AIMS Recently, new methods, including the concept of viable enhancing tumor such as EASL and mRECIST, have been proposed for substitution of the conventional WHO and RECIST criteria in hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Herein, we evaluated the differences of four methods and compared the association of these methods with the prognosis of HCC patients undergoing TACE. METHODS We retrospectively reviewed 114 consecutive newly diagnosed HCC patients who underwent TACE as initial treatment. We evaluated the intermethod agreement (κ values) between the methods and compared their association with the prognosis of HCC patients. RESULTS The κ values for EASL vs. WHO, EASL vs. RECIST, mRECIST vs. WHO, and mRECIST vs. RECIST were low, of 0.102, 0.088, 0.112, and 0.122, respectively. However, good correlations were observed for WHO vs. RECIST and EASL vs. mRECIST (κ=0.883, κ=0.759, respectively p<0.001). The median OS was 32.3 months. Hazard ratios (HR) for survival in responders compared with non-responders were 0.21 (95% CI; 0.12-0.37, p<0.001) for EASL and 0.27 (95% CI; 0.15-0.48, p<0.001) for mRECIST. The mean survival of responders was significantly longer than that of non-responders in both EASL (40.8 vs. 16.9 months, p<0.001) and mRECIST (41.1 vs. 20.7 months, p<0.001). In multivariate analysis, EASL response (HR 0.21, 95% CI 0.11-0.40, p<0.001) and mRECIST response (HR; 0.31, 95% CI, 0.17-0.59, p<0.001) were independently associated with survival. CONCLUSIONS The response assessment by EASL and mRECIST could reliably predict the survival of HCC patients undergoing TACE and could be applicable in practice in preference to the conventional WHO and RECIST criteria.

Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage

Vasoactive drugs are recommended to be started as soon as possible in suspected variceal bleeding, even before diagnostic endoscopy. However, it is still unclear whether the therapeutic efficacies of the various vasoactive drugs used are comparable. The aim of this prospective, multicenter, randomized, noninferiority trial was to characterize the effects of terlipressin, somatostatin, and octreotide when they are initiated before endoscopic treatment in patients with acute variceal bleeding. Patients with liver cirrhosis and significant upper gastrointestinal bleeding were randomly assigned to receive early administration of terlipressin, somatostatin, or octreotide, followed by endoscopic treatment. Patients with nonvariceal bleeding were excluded after endoscopy. The primary endpoint was 5‐day treatment success, defined as control of bleeding without rescue treatment, rebleeding, or mortality, with a noninferiority margin of 0.1. In total, 780 patients with variceal bleeding were enrolled: 261 in the terlipressin group; 259 in the somatostatin group; and 260 in the octreotide group. At the time of initial endoscopy, active bleeding was noted in 43.7%, 44.4%, and 43.5% of these patients, respectively (P = 0.748), and treatment success was achieved by day 5 in 86.2%, 83.4%, and 83.8% (P = 0.636), with similar rates of control of bleeding without rescue treatment (89.7%, 87.6%, and 88.1%; P = 0.752), rebleeding (3.4%, 4.8%, and 4.4%; P = 0.739), or mortality (8.0%, 8.9%, and 8.8%; P = 0.929). The absolute values of the lower bound of confidence intervals for terlipressin versus somatostatin, terlilpressin versus octreotide, and octreotide versus somatostatin were 0.095, 0.090, and 0.065, respectively. Conclusion: Hemostatic effects and safety did not differ significantly between terlipressin, somatostatin, and octreotide as adjuvants to endoscopic treatment in patients with acute gastroesophageal variceal bleeding. (Hepatology 2014;60:954–963)

Comparison of sequential and 7-, 10-, 14-d triple therapy for Helicobacter pylori infection

AIM To compare the effectiveness of sequential therapy for Helicobacter pylori (H. pylori) infection with that of triple therapy of varying durations. METHODS The 460 patients enrolled in this study had H. pylori-associated gastritis or a gastric or duodenal ulcer. After screening, H. pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7, 10 or 14 d, or a new 10-d sequential therapy. Each of the 4 treatment groups included 115 patients. The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology. RESULTS The overall eradication rate was 81.0%, and eradication rates were 75.7% for 7-d conventional triple therapy, 81.9% for 10-d conventional triple therapy, 84.4% for 14-d conventional triple therapy, and 82.0% for 10-d sequential therapy. Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy (P = 0.416 and P = 0.405, respectively). CONCLUSION There are no significant differences between 10-d sequential eradication therapy for H. pylori and any duration of standard triple treatment in Korean patients.

Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B

Aliment Pharmacol Ther 2010; 32: 498–505

Clinical Features and Prognosis of Spontaneous Bacterial Peritonitis in Korean Patients with Liver Cirrhosis: A Multicenter Retrospective Study

Background/Aims Although early recognition and treatment with effective antibiotics have lead to improvements in the prognosis of patients with spontaneous bacterial peritonitis (SBP), it remains to be a serious complication in cirrhotic patients. This study was designed to evaluate the clinical manifestations and prognosis of patients with liver cirrhosis and SBP in Korea. Methods This was a multicenter retrospective study examining 157 episodes of SBP in 145 patients with cirrhosis. SBP was diagnosed based on a polymorphonuclear cell count in ascitic fluid of >250 cells/mm3 in the absence of data compatible with secondary peritonitis. Results The mean age of the cohort was 56 years, and 121 (77%) of the 157 episodes of SBP occurred in men. Microorganisms were isolated in 66 episodes (42%): Gram-negative bacteria in 54 (81.8%), Gram-positive in 11 (16.7%), and Candida in 1. Isolated Gram-negative organisms were resistant to third-generation cephalosporin in 6 cases (17%), to ciprofloxacin in 11 (20.8%), and to penicillin in 33 (62.3%). The treatment failure and in-hospital mortality rates were 12.1% and 21%, respectively. A high Model of End-Stage Liver Disease (MELD) score, SBP caused by extended-spectrum β-lactamase-producing organisms, and hepatocellular carcinoma were independent prognostic factors of high in-hospital mortality. Conclusions SBP remains to be a serious complication with high in-hospital mortality, especially in patients with a high MELD score.

Healthy range for serum ALT and the clinical significance of "unhealthy" normal ALT levels in the Korean population

Background and Aims:  It remains unclear whether the currently‐used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. The present study was conducted to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels.

Comparison of Surrogate Serum Markers and Transient Elastography (Fibroscan) for Assessing Cirrhosis in Patients with Chronic Viral Hepatitis

BackgroundProgressive hepatic fibrosis with development of cirrhosis is a feature of almost all chronic liver diseases.AimsWe assessed the performance of Fibroscan in patients with chronic viral hepatitis, and in comparison with and combined with several surrogate serum markers for predicting cirrhosis.MethodsIn this prospective multicenter cohort study, a novel panel of serum markers was constructed and serum levels of surrogate markers of liver fibrosis and Fibroscan were compared with the stage of fibrosis in the liver biopsy specimens obtained from 121 subjects with chronic viral hepatitis. Another 159 patients were enrolled to validate the diagnostic accuracy of this novel panel.ResultsMultivariate analysis identified platelet count and procollagen III N-terminal peptide (PIIINP) as independent predictors of liver cirrhosis. The PP score (combining of platelet count and PIIINP) showed significantly better diagnostic accuracy (areas under the receiver operating characteristic curves, AUROC: 0.885) than that of previously reported serologic tests, including APRI, Forns fibrosis index, FIB-4 index and ELF algorithm, in the validation group (AUROC: 0.792, 0.740, 0.800, and 0.775, respectively). The AUROC of Fibroscan was 0.743 and the best performance was obtained by combining Fibroscan, platelet count and PIIINP, with an AUROC of 0.826. However, there was no significant difference among the AUROCs of Fibroscan alone, PP score, the combination of Fibroscan and PP score, and previously reported serologic tests in the estimation group.ConclusionsFibroscan and surrogate serum markers had similar accuracy for predicting cirrhosis, and combining Fibroscan and serum markers did not improve the accuracy.

Serum cystatin C level is a good prognostic marker in patients with cirrhotic ascites and normal serum creatinine levels

Background/Aims: Serum creatinine (Cr) is not a reliable marker for early detection of renal dysfunction in patients with cirrhotic ascites. Several reports have suggested that cystatin C (CysC) is more sensitive than Cr for detecting reduced renal function in these patients. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and a normal serum Cr level.