BACKGROUND/AIMS: The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. METHODS: A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). RESULTS: The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). CONCLUSIONS: In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population.
Aspartate Aminotransferases ; Biomarkers* ; Biopsy ; Blood Platelets ; Coinfection ; Diagnosis ; Fibrosis* ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis C, Chronic ; Hepatitis* ; Hepatitis, Chronic ; Humans ; Liver ; Liver Cirrhosis ; Platelet Count ; Prothrombin Time ; Retrospective Studies

BACKGROUND/AIMS: Hepatitis C genotypes 1 and 2 are widely distributed globally. In contrast, genotype 6 is found mainly in Southeast Asia, while genotype 6 is rare in Korea. This study aims to investigate the prevalence, risk factors and clinical characteristics of patients with genotype 6 chronic hepatitis C. METHODS: We retrospectively identified 133 HCV-infected patients who underwent HCV genotype analysis between January 2012 and December 2012, and analyzed the prevalence, risk factors and clinical characteristics of patients diagnosed with genotype 6 chronic hepatitis C. RESULTS: Among 133 patients, 53 patients (39.8%) were infected with genotype 1, 62 patients (46.6%) with genotype 2, 2 patients (1.5%) with genotype 3, 14 patients (10.5%) with genotype 6, and 2 patients (1.5%) with mixed genotypes (genotype 1 and 6). The risk factors associated with genotype 6 were acupuncture (n=4, 28.6%), intravenous drug use (n=3, 21.4%), tattoo (n=2, 14.3%), and transfusion (n=2, 14.3%). Of the 14 patients with genotype 6, 6 patients were treated with pegylated interferon and ribavirin. Five patients had reached the end of treatment. All patients reaching end of treatment for genotype 6 showed early virological response and sustained virological response. CONCLUSIONS: The prevalence of genotype 6 is 10.5% and mixed infections of genotype 1 and 6 are 1.5% in patients with chronic hepatitis C. A major potential risk factor is intravenous drug use and the treatment response rate to pegylated interferon plus ribavirin is high in patients with genotype 6 chronic hepatitis C. Large scale multicenter studies are needed.
Acupuncture Therapy ; Adult ; Aged ; Antiviral Agents/therapeutic use ; Blood Transfusion ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics/isolation & purification ; Hepatitis C, Chronic/*diagnosis/drug therapy/epidemiology ; Humans ; Interferon-alpha/therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols/therapeutic use ; Prevalence ; RNA, Viral/genetics ; Recombinant Proteins/therapeutic use ; Republic of Korea ; Retrospective Studies ; Ribavirin/therapeutic use ; Risk Factors ; Tattooing

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.
Adult ; Aged ; Antiviral Agents/*adverse effects ; Autoantibodies/blood ; Biomarkers/blood ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy ; Humans ; Incidence ; Interferon-alpha/*adverse effects ; Male ; Middle Aged ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Republic of Korea ; Retrospective Studies ; Ribavirin/*adverse effects ; Thyroid Diseases/*chemically induced/diagnosis/epidemiology/immunology/physiopathology ; Thyroid Gland/*drug effects/immunology/physiopathology ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein. METHODS: Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin. RESULTS: This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naive patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy. CONCLUSIONS: In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemoglobins/analysis ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; RNA, Viral/blood ; Republic of Korea ; Retrospective Studies ; Ribavirin/therapeutic use ; Sofosbuvir/adverse effects/*therapeutic use ; Treatment Outcome

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Aged ; Creatinine/blood ; Foot/pathology ; Gangrene/*etiology ; Hepatitis C, Chronic/complications ; Humans ; Liver Cirrhosis/complications/diagnosis ; Liver Diseases/*diagnosis/drug therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Osteomyelitis/*etiology ; Severity of Illness Index ; Toe Phalanges/radiography ; Vasoconstrictor Agents/*adverse effects/therapeutic use

BACKGROUND/AIMS: The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2. METHODS: This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared. RESULTS: The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2. CONCLUSIONS: The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring.
Adult ; Antiviral Agents/therapeutic use ; Asian Continental Ancestry Group ; Cohort Studies ; Female ; Genotype ; Hepacivirus/*genetics ; Hepatitis C, Chronic/*diagnosis/drug therapy/epidemiology ; Humans ; Liver/pathology ; Male ; Middle Aged ; Prospective Studies ; RNA, Viral/blood ; Republic of Korea ; Risk Factors ; Sexual Behavior ; Substance-Related Disorders/complications ; Tattooing

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.
Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; DNA, Viral/analysis ; Feces/*virology ; Female ; Hepatitis B/complications/*epidemiology/transmission ; Hepatitis B Core Antigens/immunology ; Hepatitis B virus/genetics/immunology ; Hepatitis C Antibodies/blood ; Humans ; Kidney Failure, Chronic/*complications/diagnosis ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Renal Dialysis ; Risk Factors

BACKGROUND: Procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) are inflammatory markers used to diagnose severe bacterial infections. We evaluated the diagnostic role of these markers and compared their accuracy for spontaneous bacterial peritonitis (SBP) associated with chronic severe hepatitis B (CSHB). METHODS: PCT and CRP concentrations, WBC count, and other hematological parameters were measured in serum from 84 well-characterized patients with CSHB, of whom 42 had SBP. Receiver operating characteristics (ROC) curve analysis was performed to assess the diagnostic accuracy. RESULTS: PCT and CRP concentrations were significantly higher in the CSHB patients with SBP (n=42) than CSHB patients without SBP (n=42). PCT and CRP concentrations were more accurate than WBC count for the diagnosis of CSHB-associated SBP. The optimal cutoff value of PCT was 0.48 ng/mL. The PCT concentration was significantly correlated with the CRP concentration and WBC count. CONCLUSIONS: Serum PCT and CRP seems to be better markers than WBC for the diagnosis of CSHB patients with SBP.
Age Factors ; Area Under Curve ; Bacterial Infections/complications/*diagnosis ; Biological Markers/blood ; C-Reactive Protein/*analysis ; Calcitonin/*blood ; Female ; Hepatitis B, Chronic/*complications ; Humans ; Leukocyte Count ; Leukocytes/cytology ; Male ; Middle Aged ; Peritonitis/complications/*diagnosis ; Protein Precursors/*blood ; ROC Curve ; Sex Factors ; Temperature

OBJECTIVE: To evaluate the mid-term prognostic value of procalcitonin (PCT), endotoxin and common inflammatory markers combining the model for end-stage liver disease (MELD) score in patients with chronic severe hepatitis. METHODS: A total of 124 chronic severe hepatitis patients were enrolled, who were hospitalized in the Department of Infectious Diseases, Xiangya Hospital, Central South University from May 2011 to December 2011. Indexes of inflammation, liver and kidney function tests and MELD were determined within 24 h after the admission, and blood samples were collected for measurement of endotoxin , procalcitonin (PCT), and C-reactin protein (CRP). The outcome was confirmed after discharge follow-up at the end of the 3rd month. According to the outcome, the 124 patients were divided into a survival group (n=58) and a death group(n=66). RESULTS: 1) Of the 124 patients, 66 died and 58 survived, with statistical difference in age, MELD score, white blood cell (WBC), polymorphonuclear (PMN), CRP and PCT by single factor analysis between the 2 groups(P<0.05). Binary logistic regression analysis indicated that age, MELD scores and PCT were highly correlated with the outcome (OR=1.07, 1.42 and 1.02 respectively, P<0.05), which could be used to predict the 3 month mid-term mortality of chronic severe hepatitis. 2)There was significant correlation between the MELD scores and the mid-term mortality. Age was positively correlated with the MELD score, and Pearson's correlation coefficient was 0.21 (P<0.05). PCT was also positively correlated with the MELD, and Spearman's correlation coefficient was 0.54 (P<0.01). 3)According to the receiver operation characteristic (ROC) curve analysis , the area under the curve (AUC) of MELD score and PCT were 0.91 and 0.77 respectively, higher than those of other indexes (P<0.01). When the MELD score was up to 30.09 or higher, the predicted mortality risk among these tested patients was the highest(82.26%). The mortality risk predicted by PCT combining MELD score and PCT alone was lower than by MELD score alone (75.00%), but the specificity of MELD score combining PCT was 100%, and the positive prediction value was 1.00. CONCLUSION Endotoxin and common inflammatory markers (WBC, PMN, and CRP) are not reliable indicators to predict the prognosis in patients with chronic-severe hepatitis. MELD score is significantly correlated with the outcome of mid-term chronic severe hepatitis, PCT and age are both positively correlated with the MELD score. PCT and age combining MELD score can be used to predict the 3 month mid-term mortality of chronic severe hepatitis. MELD score has better prognostic value than PCT. MELD score combining PCT can improve the specificity of prediction.
Adult ; Age Factors ; C-Reactive Protein ; metabolism ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; End Stage Liver Disease ; diagnosis ; mortality ; Endotoxins ; blood ; Female ; Hepatitis, Chronic ; diagnosis ; mortality ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Protein Precursors ; blood ; ROC Curve ; Severity of Illness Index ; Survival Analysis

Because Mongolia has much higher liver disease burden than any other regions of the world, it is necessary to provide information on real-time situation of chronic liver disease in Mongolia. In this article, we reviewed studies performed in Mongolia from 2000 to 2011 on seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among healthy individuals and patients with chronic liver diseases, and on the practice patterns for the management of liver cirrhosis and hepatocellular carcinoma (HCC). According to previous reports, the seroprevalence of HBV and HCV in general population in Mongolia is very high (11.8% and 15% for HBV and HCV, respectively). Liver cirrhosis is also highly prevalent, and mortality from liver cirrhosis remained high for the past decade (about 30 deaths per 100,000 populations per year). Among patients with cirrhosis, 40% and 39% are positive for HBsAg and anti-HCV, respectively, and 20% are positive for both. The seroprevalence is similar for HCC and more than 90% of HCC patients are positive for either HBV or HCV. The incidence of HCC in Mongolia is currently among the highest in the world. The mortality from HCC is also very high (52.2 deaths per 100,000 persons per year in 2010). Partly due to the lack of established surveillance systems, most cases of HCC are diagnosed at an advanced stage. The mortality from liver cirrhosis and HCC in Mongolia may be reduced by implementation of antiviral therapy program and control of alcohol consumption.
Carcinoma, Hepatocellular/blood/diagnosis/*epidemiology/mortality/therapy ; Hepatitis B, Chronic/epidemiology ; Hepatitis C, Chronic/epidemiology ; Humans ; Liver Cirrhosis/epidemiology ; Liver Diseases/blood/diagnosis/*epidemiology/mortality/therapy ; Liver Neoplasms/blood/diagnosis/*epidemiology/mortality/therapy ; Mongolia/epidemiology ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors ; Seroepidemiologic Studies ; Time Factors