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The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6 mo) and long-term (6-120 mo) survival of patients with decompensated cirrhosis., Methods: We performed a 10-year observation analysis using data from the Epidemiology and Natural History of Liver Cirrhosis study of patients with decompensated liver cirrhosis in Korea. Of the entire cohort (1595 patients enrolled at onset of decompensation since 2005), our analysis comprised 295 patients who immediately began treatment with entecavir (n = 179) or lamivudine (n = 116) after decompensation. We collected laboratory test results, data on hepatocellular carcinoma (HCC) development, and Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores. The mean follow-up time was 62.3 ± 36.5 months. The primary end point was time of liver transplant-free survival., Results: The median survival time was 7.7 years; 60.1% of patients survived for 5 years and 45.7% survived for 10 years without liver transplantation. An MVR was observed in 116 patients (39.3%); these patients had significantly longer times of transplant-free survival than patients without MVR. Survival times associated with the occurrence of HCC; survival of patients without HCC was excellent if they survived the first 6 months after initiation of antiviral therapy, whereas the survival rates of patients with HCC decreased persistently over time. A baseline MELD score above 20 and multiple complications were associated with short-term mortality. MVR was the factor most strongly associated with long-term transplant-free survival. Significantly higher proportions of patients who received entecavir survived 10 years compared with patients who received lamivudine, but no difference was observed among patients with MVRs. Patients with MVRs had significant improvement in hepatic function over time, but nonsignificant reductions in risk of HCC or HCC-related mortality., Conclusions: In a 10-year observation study of patients in Korea with HBV-related decompensated cirrhosis, we found baseline MELD score and MVR to entecavir or lamivudine to associate with short- and long-term transplant-free survival. The benefits of an MVR are maintained for up to 10 years even after decompensation, but patients are still at risk for HCC., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC)., Methods: The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements., Results: With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001)., Conclusions: CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) subgenotypes, the spectrum of mutations in the precore/core region through phylogenetic analysis, and the relevance of viral characteristics in disease progression in Korean patients., Methods: 133 patients with chronic HBV infection were enrolled. The precore and core region of HBV was amplified and sequenced. Phylogenetic analysis was performed for subgenotyping and the changes of nucleotides and amino acid were compared in liver disease stages., Results: HBV/C2 subgenotype was predominant in chronic HBV carriers (98.5%), followed by HBV/A2 (0.75%) and HBV/C7 (0.75%). The mutations of the precore region were not different between liver disease stages. However, amino acid changes in the cytotoxic T lymphocyte epitope (p < 0.020), CD4+ T cell epitope (p < 0.027), or B cell epitope (p < 0.029) were significantly higher in liver cirrhosis patients than in chronic hepatitis patients, but not in hepatocellular carcinoma patients., Conclusion: HBV/C2 is the most prevalent subgenotype in Korea, and HBV/C7 subgenotype found in the Philippines was first identified in the Korean population. Mutations in immune epitopes within the core gene were significantly associated with disease progression., (Copyright © 2011 S. Karger AG, Basel.)

Liver cirrhosis represents the final common pathway of virtually all chronic liver diseases, and is characterized by an accumulation of extracellular matrix rich in fibrillar collagens. Patients with cirrhosis are at risk of developing many potential complications. The most common complication seen in patients with liver cirrhosis is ascites, and the most lethal one is bleeding varices. Other intermediate and late stage complications include spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome. The mortality and morbidity attributable to liver disease in Korea have decreased continuously over the past decades, probably due to the implementation of universal vaccination and potent antiviral therapies. In addition, recent advances in the understanding of the pathophysiology of cirrhosis and in various management approaches to cirrhosis complications will contribute to the steady improvement in patient outcomes in this country. This review article outlines recent changes in etiologies and prognosis, and the advances in management of cirrhosis in Korea.

Background/aims: In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria., Methods: Pre-operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated., Results: The 1- and 3-year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface (P=0.014) and progressive disease after pretransplant treatment (P=0.038). The 2-year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively (P<0.001). The 2-year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors (P=0.022)., Conclusions: In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface.

Background/aim: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population., Methods: One hundred and thirty-seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules., Results: In class I antigens, the frequencies of HLA-A3 (relative risk (RR)=3.5, P<0.04), HLA-B35 (RR=2.0, P<0.03), and HLA-B46 (RR=2.5, P<0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1*0803, DQB1*0601 and DQB1*0604 were significantly higher in chronic HCV carriers than in controls (RR=2.5, P<0.005; RR=1.8, P<0.05; RR=1.9, P<0.04, respectively). On the other hand, the frequencies of DRB1*0301, DQA1*0501 and DQB1*0201 were significantly lower in chronic HCV carriers than in normal controls (RR=0.2, P<0.03; RR=0.4, P<0.004; RR=0.5, P<0.02, respectively). The haplotype DRB1*0803-DQB1*0601 significantly increased (RR=2.5, P<0.02) while the DQA1*0501-DQB1*0201 significantly decreased (RR=0.2, P<0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1*0803 and DQB1*0601 were associated with HLA-B46, particularly in patients with chronic HCV carriers., Conclusions: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population.

Hepatitis B virus (HBV) is one of the major causative agents of chronic liver diseases in Korea. HBV has been classified into 8 genotypes by a divergence of >8% in the entire genomic sequence, and have distinct geographic distributions. There are limited data on the relevance between HBV genotypes and clinical outcomes in Korea. To investigate the clinical feature relating to HBV genotype in Korea, a total 120 serum samples with HBsAg (65 from Seoul and 55 from the other city in Korea) were obtained from each 30 chronic HBV carriers with asymptomatic carrier (ASC), chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBV genotype was determined by either enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies against genotype-specific epitopes in the preS2-region or the direct sequencing of small S gene. HBV genotypes were determined in 105 (87.5%) of 120 samples. HBV genotype C was identified in all HBV carriers with ASC, CH, LC, and HCC. Genotypes A, B, D, E, F and G were not detected in any of them. Genotype C HBV prevails predominantly among chronic carriers of the virus in Korea, irrespective of their clinical stages of liver disease and geographic origin.

Objective: The aim of this study was to evaluate retrospectively the long-term effects of lamivudine in 461 Korean patients with chronic hepatitis B who were treated for more than 12 months., Methods: The annual rates of virological response and breakthrough were examined and the predictive factors for post-treatment relapse in 114 patients who achieved hepatitis B e antigen (HBeAg) loss or seroconversion after lamivudine therapy were also analyzed., Results: During follow-up, the rates of HBeAg seroconversion after 1, 2, 3, 4 and 5 years of treatment were 22.9, 33.2, 47.6, 54.2 and 58.8%, respectively, while those for virological breakthrough at 1, 2, 3 and 4 years were 8.2, 41.7, 55.7 and 64.8%, respectively. Ninety-five patients (20.6%) had HBeAg seroconversion and 19 (4.1%) showed HBeAg loss alone with disappearance of hepatitis B virus DNA in serum. Seroconversion was higher with prolonged treatment in patients who had elevated serum alanine aminotransferase. The cumulative relapse rates in the seroconversion group were 52.0 and 55.7% 1 and 2 years after treatment, respectively. Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged 12 months after seroconversion had the lowest relapse rate (p < 0.001)., Conclusions: These results suggest that additional treatment for over 12 months after HBeAg seroconversion in younger patients may produce a better long-term outcome., (Copyright (c) 2005 S. Karger AG, Basel.)

Recently, we reported that Qi-therapy may be beneficial in reducing negative psychological symptoms and increasing melatonin levels, neutrophil function and natural killer cell cytotoxicity in young subjects. However, there is little scientific evidence of its efficacy in elderly subjects. Therefore, this study was designed to investigate the effects of Qi-therapy on anxiety, depression, fatigue, pain and blood pressure in elderly subjects. Ninety-four elderly subjects were randomly assigned to either Qi-therapy (n=47) or mimic therapy (n=47) groups. Both groups received a 10-min intervention period once using similar procedures. The Qi-therapy group exhibited greater reduction in anxiety, depression, fatigue, pain level and blood pressure compared to the placebo group; the difference in anxiety was significant (P=0.014). These results suggest that even a brief application of Qi-therapy may exert a positive psychological and physiological effect. However, further research is necessary in order to fully understand the long-term impact of Qi-therapy on psychological health and the cardiovascular system.