Hyung Joon Yim

Current status of liver diseases in Korea: Hepatitis B

Hepatitis B virus (HBV) infection is the one of the most common causes of the liver diseases in Korea. Since the discovery of Australia antigen (hepatitis associated antigen, or HBsAg later), hepatitis associated antigen was tested widely. HBsAg was detected in 6.6-8.6% in 1980s. Later, it decreased to 5.7% in 1990s. Remarkably, seropositivity of the children deceased to 0.2% after the nationwide vaccination program. Although hepatitis B vaccines are highly effective, the failure rate of perinatal prophylaxis in babies born to HBsAg positive mother was reported to be 4.25%. Treatment of chronic hepatitis B was initiated after the introduction of interferon alpha. Lamivudine opened a new era of oral antiviral agent, and it has been widely used in Korea since 1999. Adefovir was proven to have a good efficacy for lamivudine-resistant chronic hepatitis B. Newer potent antiviral agents such as entecavir, clevudine, and telbivudine are available currently. Further studies are warranted for understanding factors influencing natural history, improving treatment outcomes, and overcoming vaccine non-response.

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)

Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: A randomised, non-inferiority, open trial

BACKGROUND & AIMS Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. METHODS In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddreys discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. RESULTS The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. CONCLUSIONS The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Comparative study of helicobacter pylori eradication rates with 5-day quadruple concomitant therapy and 7-day standard triple therapy

Background: Several studies have shown the superiority of concomitant quadruple therapy containing 3 antibiotics over triple therapy for Helicobacter pylori infection. The aim of this study was to compare concomitant quadruple therapy with standard triple therapy for first-line H. pylori eradication. Methods: A total of 270 patients with proven H. pylori infection were randomly assigned to one of 2 regimens: amoxicillin 1000 mg with clarithromycin 500 mg and lansoprazole 30 mg twice daily for 7 days (triple therapy) or amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice daily for 5 days (concomitant therapy). The success of eradication was evaluated 4 to 5 weeks after completion of treatment. Results: Eradication rates were 86.1% in the triple therapy and 91.4% in the concomitant therapy (per protocol), but the difference was not statistically significant. Mild adverse events were more frequently reported in the concomitant-therapy group (35.6%) than in the triple-therapy group (25.2%) (P=0.09). Conclusions: Five-day quadruple concomitant therapy eradicated H. pylori in over 90% of patients. Accordingly, concomitant therapy is thought to be a promising alternative to triple therapy as a first-line treatment regimen for H. pylori eradication.

A nationwide seroepidemiology of hepatitis C virus infection in South Korea

The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large‐scale survey.

Chronic hepatitis B: whom to treat and for how long? Propositions, challenges, and future directions

Recent guidelines of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver 2008 update of the “Asian-Pacific consensus statement on the management of chronic hepatitis B” offer comprehensive recommendations for the general management of chronic hepatitis B (CHB). These recommendations highlight preferred approaches to the prevention, diagnosis, and treatment of CHB. Nonetheless, the results of recent studies have led to an improved understanding of the disease and a belief that current recommendations on specific therapeutic considerations, including CHB treatment initiation and cessation criteria, particularly in patient populations with special circumstances, can be improved. Twelve experts from the Asia-Pacific region formed the Asia-Pacific Panel Recommendations for the Optimal Management of Chronic Hepatitis B (APPROACH) Working Group to review, challenge, and assess relevant new data and inform future updates of CHB treatment guidelines. The significance of and controversy about reported findings were discussed and debated in an expert meeting of the Working Group in Beijing, China, in November 2008. This review paper attempts to identify areas requiring improved CHB management and provide suggestions for future guideline updates, with special emphasis on treatment initiation and duration.

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.

Genetic analysis of HAV strains isolated from patients with acute hepatitis in Korea, 2005–2006

Hepatitis A virus (HAV) is a causative agent of acute viral hepatitis, which represents a significant public health problem. HAV is usually transmitted by oral‐fecal route and prevalent not only in developing countries but also in developed countries worldwide. To characterize the HAV wild type strains circulating in Korea, the VP3/VP1 and VP1/P2A junction regions were detected by RT‐PCR from HAV IgM positives during 2005 and 2006. Among 160 HAV IgM positive sera, 30% (n = 48) were positive for HAV RNA. Additionally, the VP3/VP1 junction regions were detected all six stools, which collected from outbreak in Gyeonggi province. Phylogenetic analysis of the sequences obtained from 54 distinct HAV isolates revealed that most of the strains (n = 45) belonged to genotype IA and the others including nine strains belonged to genotype IIIA. Interestingly, a Q → S amino acid change was dominantly observed at position 810 of the VP1/P2A junction region in 14 isolates. The molecular epidemiology of HAV infection in Korea has changed with the co‐circulation of at least two genotypes and 810Q → S amino acid substitutions were found to be prevalent. These results strongly suggest that various HAV strains, including genotype IIIA, might be imported from high‐endemic countries into Korea. J. Med. Virol. 80:777–784, 2008.

Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide.

The aim of the present study was to determinethe efficacy of a new combination regimen including anantioxidant, a proton pump inhibitor, and antibioticsagainst Helicobacter pylori and to document the changes of oxidative stress and cytokinesinvolved in H. pylori-associated gastric inflammation.From 57 patients with endoscopically diagnosed gastricand/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimenswere taken for the diagnosis of H. pylori and for theexperimental measures. The patients were then treatedeither with lansoprazole 30 mg + amoxicillin 1.5 g (LAgroup; 21 patients) or lansoprazole 30 mg amoxicillin1.5 g + rebamipide 300 mg (LAM group; 36 patients) fortwo weeks. Four weeks after the initiation of treatment,the patients were endoscoped again and biopsy specimens were obtained. Mucosalmalondialdehyde (MDA) levels; myeloperoxidase (MPO)activities; superoxide dismutase; catalase; glutathioneperoxidase; cytokines IL-1, IL-6, TNF-α; andchemokines IL-8, GRO-α, RANTES (regulated onactivation normal T expressed and secreted) weremeasured. Using paraffin-embedded tissue sections, insitu terminal deoxyribonucleotide transferase (TdT)mediated dUTP nick end labeling (TUNEL) for apoptosisand immunohistochemical staining for inducible nitricoxide synthase (iNOS) were performed. Two weeks oftreatment with the LA regimen resulted in 57.4%eradication rates of H. pylori, whereas two weeks oftreatment with the LAM regimen resulted in 75.0%eradication rates. Eradication rates between these twogroups were statistically significantly different (P< 0.05). Mucosal MDA levels and MPO activities weresignificantly lower in the LAM group than the LA group.Mucosal levels of cytokines IL-1, IL-6, and TNF-αand of chemokines IL-8, GRO-α, and RANTES were all significantly decreased after the treatmentof H. pylori, especially so in the LAM group. Theapoptotic index and iNOS score were significantlyreduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradicationregimen against H. pylori has advantages either inaugmenting the eradication rates of H. pylori or indecreasing the oxidative stress and cytokines levelsgenerated by H. pylori infection.