Yong Jin Jung

c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells.

MicroRNAs (miRNAs) regulate post‐transcriptional gene expression in various physiological and pathological processes, including viral infections. The miR‐17‐92 cluster encodes six miRNAs (miR‐17‐5p, miR‐18a, miR‐19a, miR‐19b, miR‐20a, and miR‐92a‐1) which are transactivated by c‐Myc. Because hepatitis B virus transactivates c‐Myc, the interaction between the miR‐17‐92 cluster and HBV replication was examined in this study. Inducing HBV replication in a human hepatoma cell line increased miR‐17‐5p, miR‐20a and miR‐92a‐1 expression. HBV‐induced overexpression of miR‐17‐92 was reversed by c‐Myc knockdown. Antisense peptide nucleic acids against miR‐20a and miR‐92a‐1 augmented HBV replication. A computational analysis yielded potential binding sites for miR‐20a and miR‐92a‐1 in the HBV genome. The direct interaction between these two miRNAs and target regions in HBV transcripts was confirmed by luciferase reporter analysis. These results demonstrated negative feedback suppression of HBV replication by the miR‐17‐92 polycistron. J. Med. Virol. 85: 969–978, 2013.

Erratum to: Add-On Adefovir Is Superior to a Switch to Entecavir as Rescue Therapy for Lamivudine-Resistant Chronic Hepatitis B

Serum ALT levels decreased during the treatment period in both groups (Table 2). However, no significant differences were found between the two groups in the mean reduction and normalization of ALT at week 48. Among HBeAgpositive patients, HBeAg seroconversion (66.7% in the ETV group vs. 38.4% in the add-on ADV group) and the mean time to HBeAg seroconversion (11.83 ± 8.95 months in the ETV group vs. 5.40 ± 1.45 months in the add-on ADV group) were similar in the two groups (P = 0.229 and P = 0.190).

Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis

The aims of this study were to investigate whether acid suppressive therapy increases the risk of spontaneous bacterial peritonitis (SBP) and to define factors associated with mortality in cirrhotic patients with SBP.

Evaluation of hernia repair operation in Child-Turcotte-Pugh class C cirrhosis and refractory ascites.

Background and Aim:  Abdominal wall hernia is a common feature of decompensated liver cirrhosis and frequently causes life‐threatening complications or severe pain. However, there have been no data reported on postoperative mortality, hepatic functional deterioration and recurrence rate according to Child–Turcotte–Pugh (CTP) class and to the presence of refractory ascites.

PUTATIVE ASSOCIATION OF FAS AND FASL GENE POLYMORPHISMS WITH CLINICAL OUTCOMES OF HEPATITIS B VIRUS INFECTION

Objective:Fas/FasL polymorphisms, which are related to apoptosis, might influence the clearance of hepatitis B virus (HBV) infection and the occurrence of hepatocellular carcinoma (HCC). This study was performed to determine whether Fas and FasL promoter polymorphisms are associated with clinical outcome in chronic HBV infection. Methods: A total of 1,095 Korean subjects were prospectively allocated to two different groups: ‘the chronic carrier group’ (CC; n = 666), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and ‘the spontaneous recovery group’ (SR; n = 429), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. In addition, the CC group was subcategorized into chronic hepatitis and HCC subgroups. Fas promoter polymorphisms at –1377G>A and –670A>G and the FasL promoter polymorphism at –844C>T were analyzed for and the genotype distributions of subjects were compared. Results: There were no significant associations between Fas or FasL promoter polymorphism with the HBV clearance and HBeAg clearance. However, –1377G>A in Fas promoter region showed protective effect to HCC occurrence (RH = 0.70, p = 0.03). Conclusions:Fas–1377G>A polymorphisms might be involved in the pathogenesis of human HCC.

Clinical features of acute renal failure associated with hepatitis A virus infection.

Summary.  Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self‐limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non‐ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non‐ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P < 0.001), prothrombin time (PT) (International normalized ratio, median 1.72 vs 1.10, P < 0.001), and total bilirubin level (median: 9.6 mg/dL vs 6.3 mg/dL, P = 0.04) were significantly higher in the ARF than in the non‐ARF group. Twelve patients (80%) recovered completely with haemodialysis (seven patients, 46.7%) or only conservative management (five patients, 33.3%), while one patient underwent liver transplantation because of fulminant hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non‐ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.

Role of ascites adenosine deaminase in differentiating between tuberculous peritonitis and peritoneal carcinomatosis

AIM To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC). METHODS A retrospective analysis of data was performed on consecutive patients who underwent peritoneoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS Serum c-reactive protein (7.88 ± 6.62 mg/dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serum-ascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.

The Role of Spleen Stiffness in Determining the Severity and Bleeding Risk of Esophageal Varices in Cirrhotic Patients

AbstractEsophageal varix and its hemorrhage are serious complications of liver cirrhosis. Recent studies have focused on noninvasive prediction of esophageal varices. We attempted to evaluate the association of liver and spleen stiffness (LS and SS) as measured by acoustic radiation force impulse imaging, with the presence and severity of esophageal varices and variceal hemorrhage in cirrhotic patients.We measured LS and SS, along with endoscopic examination of esophageal varices for a total of 125 cirrhotic patients at a single referral hospital in this prospective observational study. The diagnostic utility of noninvasive methods for identifying varices and their bleeding risk was compared, including LS, SS, spleen length, Child-Pugh score, and various serum fibrosis indices.Esophageal varices were present in 77 patients (61.6%). SS was significantly higher in patients with varices than in those without varices (3.58 ± 0.47 vs 3.02 ± 0.49; P < 0.001). A tendency toward increasing SS levels was observed with increasing severity of varices (no varix, 3.02 ± 0.49; F1, 3.39 ± 0.51; F2, 3.60 ± 0.42; F3, 3.85 ± 0.37; P < 0.001). SS was significantly higher in patients who experienced variceal hemorrhage than in those who did not (3.80 ± 0.36 vs 3.20 ± 0.51; P = 0.002). An optimal cut-off value of SS for high-risk varices (≥F2) or variceal hemorrhage was 3.40 m/s.SS was significantly correlated with the presence, severity, and bleeding risk of esophageal varices. Prompt endoscopic evaluation of variceal status and prophylactic measures based on the SS may be warranted for cirrhotic patients.

Prospective Comparison of Noninvasive Fibrosis Assessment to Predict Advanced Fibrosis or Cirrhosis in Asian Patients With Hepatitis C.

Goals and Background: The diagnostic role of noninvasive fibrosis assessment, which can obviate liver biopsy in Asian patients with hepatitis C, remains controversial. This study aimed to evaluate the diagnostic accuracy of noninvasive fibrosis assessment to predict advanced fibrosis or cirrhosis in Asian patients with hepatitis C. Study: A total of 101 antiviral treatment–naive patients with hepatitis C were prospectively enrolled between March 2011 and March 2013. Liver stiffness was measured by acoustic radiation force impulse (ARFI) elastography. At the same time, liver biopsy was performed to obtain histologic data of hepatic fibrosis. Diagnostic measurements of serum fibrosis indices and ARFI imaging were compared with predicted advanced fibrosis or cirrhosis by analyzing the area under the receiver operating characteristic (AUROC) curve. Results: The median age of the study population was 59 years (range, 25 to 82 y). Aspartate aminotransferase to alanine aminotransferase ratio (AAR), Fib-4, Forns index, aspartate aminotransferase to platelet ratio index (APRI), and Lok index showed significant, positive correlations with METAVIR stages (P<0.001). Fib-4 had the greatest AUROC for advanced fibrosis (≥F3) (0.864; 95% CI, 0.793-0.934), and the Lok index had the highest AUROC for predicting cirrhosis (F4) (0.847; 95% CI, 0.767-0.927). A tendency toward increasing liver stiffness existed in a graded manner across METAVIR stages (P<0.001). Conclusions: Fib-4 and Lok index were useful noninvasive fibrosis indices for predicting advanced fibrosis and cirrhosis in Asian patients with hepatitis C. In addition, ARFI elastography exhibited acceptable diagnostic performance in the assessment of hepatic fibrosis in patients with hepatitis C.

Characterization of acute-on-chronic liver failure and prediction of mortality in Asian patients with active alcoholism.

Alcoholic liver diseases often evolve to acute‐on‐chronic liver failure (ACLF), which increases the risk of (multi‐)organ failure and death. We investigated the development and characteristics of alcohol‐related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism.