Myung Seok Lee

Seroepidemiology of HBV Infection in South Korea , 1995 through 1999

Background : We analyzed serologic data that were obtained from the Korea Association of Health from 1995 to 1999 to estimate the reliable prevalence of HBV in South Korea. Methods : 603,375, 639,465, 621,476, 612,705 and 650,398 serum samples were annually tested for HBsAg. Of HBsAg positive persons whose serum samples were available, HBeAg positivity was checked. Results : HBsAg positivities among subjects between 6 and 19 years old were 8.2%, 3.9%, 2.1%, 2.6% and 1.3%. HBsAg positivities among subjects above 20 years old were 8.9%, 6.4%, 5.9%, 5.4% and 5.4%. The positive rates of HBeAg were 39.8 to 62.9% among subjects between 6 and 19 years old, and 18.3 to 37.9% among persons above 20 years old, in each year. In both subgroups, HBsAg positivity in the latter year was significantly lower than that in the former year (p<0.001). It also showed that HBsAg positivities among subjects between 6 and 19 years old have been significantly lower than those among subjects above 20 years old, but those of HBeAg the exact reverse of HBsAg since 1996 (p<0.001). Conclusions : It was observed that prevalence of HBV infection in the late 1990s, especially in the group between 6 and 19 years old, was conspicuously lower than that in the past. The nationwide vaccination programme might be one of the most important contributors to this tendency in Korea.

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection.

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009.

Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial.

Management of lamivudine‐resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported.

Helicobacter pylori infection and peptic ulcer disease in patients with liver cirrhosis.

Background/Aims We investigated the prevalence and relationship of peptic ulcer disease and Helicobacter pylori infection to liver cirrhosis. Methods We examined 288 patients with liver cirrhosis, 322 patients with non-ulcer dyspepsia, and 339 patients with peptic ulcer disease. Rapid urease test and Wright-Giemsa staining were used for diagnosis of H. pylori infection. Results The prevalence of peptic ulcer disease in patients with cirrhosis was 24.3%. The prevalence of peptic ulcer disease in patients with cirrhosis divided into Child-Pugh classes A, B, and C was 22.3%, 21.0%, and 31.3%, respectively (p>0.05). The prevalence of H. pylori infection in the patients with cirrhosis, non-ulcer dyspepsia, and peptic ulcer without chronic liver disease were 35.1%, 62.4%, and 73.7%, respectively (p<0.001). The prevalence of H. pylori infection did not differ depending on whether there was peptic ulcer (35.6%) or not (34.9%) in patients with liver cirrhosis (p>0.05). The prevalence of H. pylori infection in patients with hepatitis virus-related liver cirrhosis and in the patients with alcohol-related liver cirrhosis was 42.5% and 22.0%, respectively (p<0.001). The prevalence of H. pylori infection in patients with Child-Pugh classes A, B, and C liver cirrhosis was 51.5%, 30.5%, and 20.0%, respectively (p<0.001). Conclusions Factors other than H. pylori may be involved in the pathogenesis of peptic ulcer disease in the setting of liver cirrhosis.

Early Viral Kinetics of Telbivudine and Entecavir: Results of a 12-Week Randomized Exploratory Study with Patients with HBeAg-Positive Chronic Hepatitis B

ABSTRACT We characterized the early viral kinetic profiles of telbivudine and entecavir and the effects of these potent nucleoside analogs on hepatitis B virus (HBV) DNA and alanine aminotransferase levels in adults with hepatitis B e antigen-positive compensated chronic hepatitis B. Forty-four patients were enrolled in this open-label, parallel-group, multicenter study and randomized to receive telbivudine or entecavir for 12 weeks. Reductions in hepatitis B virus DNA and alanine aminotransferase levels from baseline to weeks 2, 4, 8, and 12 were assessed. Viral kinetic parameters, including viral clearance per day, loss of infected cells per day, and efficiency of inhibition of viral production, were estimated by using a biphasic mathematical model. Statistical analyses were limited to descriptive analyses. The 2 treatment groups achieved similar reductions in HBV DNA and alanine aminotransferase levels. Mean reductions in levels of hepatitis B virus DNA at week 12 were 6.6 ± 1.6 and 6.5 ± 1.5 log10 copies/ml for the telbivudine- and entecavir-treated patients, respectively. There were no significant differences between groups in values for mean viral clearance per day, mean loss of infected cells per day, or efficiency of blocking viral production. The safety profiles for both medications were favorable. During the first 12 weeks of treatment, telbivudine and entecavir demonstrated similar antiviral potencies, resulting in a rapid and profound suppression of serum hepatitis B virus DNA and reduction of alanine aminotransferase levels. No differences in the effects of these 2 agents on early viral kinetics were observed. Both medications were well tolerated.

Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

AIM To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

Prevalence of Minimal Change Lesions in Patients with Non-Erosive Reflux Disease: A Case-Control Study

Background/Aims: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). Methods: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). Results: Overall frequency of MC (≥1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72–9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. Conclusions: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

Clinical Characteristics and Outcomes of Acute Hepatitis A in Korea: A Nationwide Multicenter Study

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea. Graphical Abstract

Clinical characteristics of patients with Mycoplasma pneumoniae-related acute hepatitis.

Background/Aims: Although the hepatobiliary manifestations of Mycoplasma pneumoniae infection have been described in several previous studies, controversies still remain. The aim of this study was to evaluate the clinical characteristics of patients with M. pneumoniae-related hepatitis and compare to those with M. pneumoniae infection but not hepatitis. Methods: We reviewed the medical chart of patients diagnosed with M. pneumoniae infection serologically. Results: Among the 117 patients with M. pneumoniae infection enrolled in the study, 25 showed acute hepatitis without any evidence of another cause. Patients with hepatitis presented with prodromal symptoms more frequently and also had a higher body temperature and C-reactive protein (CRP) levels than patients without hepatitis. Frequencies of respiratory tract involvement were not different between two groups. Clinical signs recovered within three weeks in both groups following the institution of antibiotic therapy. Multivariate analysis revealed that male sex, age <40 years, and high CRP levels were significantly linked to M. pneumoniae-related hepatitis. Conclusions: We found that acute hepatitis associated with M. pneumoniae occurred in about 21% of all M. pneumoniae infections, and gender, age, and CRP levels were factors related to the occurrence of M. pneumoniae-related hepatitis.

Genotypic shift of the hepatitis A virus and its clinical impact on acute hepatitis A in Korea: a nationwide multicenter study

Abstract Background: The genotypic shift of hepatitis A virus (HAV) and its correlation with clinical course has not been evaluated in acute hepatitis A (AHA). Methods: From June 2007 to May 2009, we prospectively enrolled 546 AHA patients. We performed a nested reverse transcriptase polymerase chain reaction (RT-PCR) using the serum samples in addition to phylogenetic analysis, then we compared patient clinical features. Results: Among 351 successfully genotyped patients, we found genotype IIIA in 178 patients (51%) and IA in 173 patients (49%). The sequences of genotype IA are identical to previously reported Korean genotype IA, and the new IIIA genotype is closely related to NOR24/Norway. We retrospectively analyzed 41 AHA samples collected from 2000 to 2006 and found that all of them were genotype IA. Patients with genotype IIIA showed significantly higher levels of aspartate aminotransferase, higher levels of alanine aminotransferase, and lower platelet counts than patients with genotype IA when comparing baseline laboratory data or peak/lowest laboratory data during the disease course. However, there were no differences in duration of hospital stay, incidence of cholestatic hepatitis, acute kidney injury, and acute liver failure, or mortality between them. Conclusions: A genotypic shift of the HAV was identified in Korean AHA subjects, and genotype IIIA HAV has become endemic. Although there were significant differences in the biochemical responses of AHA between genotype IA and genotype IIIA patients, we did not detect any differences in clinical outcomes such as complications or mortality.