Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Esophageal and Gastric Varices/complications/prevention & control ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Ultrasonography

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Aspartate Aminotransferases/blood ; Bilirubin/analysis ; Cholestasis/*drug therapy ; Guillain-Barre Syndrome/complications/*diagnosis ; Hepatitis E/*diagnosis/etiology ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin M/blood ; Liver/pathology ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Republic of Korea ; Steroids/*therapeutic use

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.
Biomarkers/*blood ; DNA, Viral/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/prevention & control ; Humans ; Liver Cirrhosis/etiology ; Organic Anion Transporters, Sodium-Dependent/genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Symporters/genetics

BACKGROUND/AIMS: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. METHODS: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. RESULTS: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The < or = 30-day group was characterized by higher peak alanine aminotransferase (ALT) level and a high proportion of patients with maintenance of first-line antituberculous drugs compared to the > 30-day group. In subgroup analysis, the < or = 7-day group was characterized by higher baseline aspartate aminotransferase and ALT, high proportion of patients with maintenance of first-line antituberculous drugs, and high proportion of patients with extrapulmonary tuberculosis compared to patients with ADIH that developed beyond 7 days. In multivariate analysis, serum ALT > 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. CONCLUSIONS: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.
Adult ; Aged ; Alanine Transaminase/blood ; Antitubercular Agents/*adverse effects ; Aspartate Aminotransferases/blood ; Biomarkers/blood ; Chemical and Drug Induced Liver Injury/blood/*diagnosis/etiology ; Chi-Square Distribution ; Clinical Enzyme Tests ; Coinfection ; Drug Monitoring/*methods ; Drug Therapy, Combination ; Early Diagnosis ; Female ; Hepatitis/complications/diagnosis ; Humans ; *Liver Function Tests ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Time Factors

OBJECTIVEThis study explored the correlation of longitudinal changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with the incidence of metabolic syndrome (Mets) based on a dynamic health examination cohort.

METHODSA Mets-free dynamic cohort involving 4541 participants who underwent at least three health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definition that included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation (GEE) model was used to analyze multivariate relative risk (RR) of repeated observations of ALT and AST in quartiles for Mets or its components according to gender.

RESULTSIn all, 826 Mets cases were reported. Adjustment of relevant parameters indicated that time-varying changes in ALT and AST levels were positively associated with the incidence of Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in male participants. These associations were consistently observed in the following subgroups: participants with ALT and AST levels of <40 U/L, participants with of <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component.

CONCLUSIONThese results suggested that elevated serum ALT and AST levels were early biomarkers of Mets or its components.

Adult ; Aged ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Biomarkers ; blood ; China ; epidemiology ; Cohort Studies ; Female ; Hepatitis ; complications ; epidemiology ; etiology ; Humans ; Incidence ; Liver ; enzymology ; physiopathology ; Male ; Metabolic Syndrome ; complications ; diagnosis ; enzymology ; epidemiology ; Middle Aged ; Young Adult

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

BACKGROUND/AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. METHODS: In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. RESULTS: Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16+/-5 to 14+/-10 (mean +/- SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (> or =2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). CONCLUSIONS: Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Hepatitis B/complications/*drug therapy ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Humans ; Lamivudine/*therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/mortality ; Male ; Middle Aged ; Odds Ratio ; Organophosphonates/*therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Survival Rate

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

BACKGROUND/AIMS: Relapse has been reported after stopping nucleos(t)ide (NUC) therapy in the majority of chronic HBeAg negative hepatitis patients. However, the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not well known. We investigated the frequency of relapse in HBeAg negative CHB patients receiving NUC therapy. METHODS: The NUC therapy was discontinued at least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients. Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal range. Virological relapse was defined as HBV DNA >2,000 IU/mL. RESULTS: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virological relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1 year sustained response. Of these factors, cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year virological relapse rate. Baseline HBV DNA and total treatment duration tended to be associated with virological relapse. CONCLUSIONS: Virological relapse developed in the majority (73.3%) of HBeAg negative CHB patients and clinical relapse developed in the half (53.3%) of patients at 1 year off therapy. Cirrhosis may be associated with the low rate of virological relapse.
Adult ; Age Factors ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Aspartate Aminotransferases/blood ; DNA, Viral/analysis ; Drug Administration Schedule ; Female ; Hepatitis B e Antigens/*analysis ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/diagnosis/etiology ; Male ; Middle Aged ; Nucleotides/*therapeutic use ; Recurrence ; Sex Factors

This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.
Acute Disease ; Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Food Handling ; Hepatitis A/*diagnosis/etiology/prevention & control ; Hepatitis A Antibodies/blood ; Humans ; Immunoglobulin M/blood ; Infant ; Infant, Newborn ; Interviews as Topic ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Referral and Consultation ; Risk Factors ; Seafood ; Travel ; Vaccination ; Young Adult