Acute Disease ; Anemia, Hemolytic ; diagnosis ; etiology ; Coombs Test ; Hepatitis E ; complications ; diagnosis ; Humans ; Male ; Middle Aged

BACKGROUND AND AIMS: The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea. METHODS: We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E. RESULTS: The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1+/-4.38, 38.7+/-11.72, 45.3+/-17.62 and 32.4+/-6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area. CONCLUSIONS: The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future.
Acute Disease ; Adult ; Aged ; Cohort Studies ; Female ; Hepatitis A/diagnosis/epidemiology/virology ; Hepatitis B/diagnosis/epidemiology/virology ; Hepatitis C/diagnosis/epidemiology/virology ; Hepatitis D/diagnosis/epidemiology/etiology ; Hepatitis E/diagnosis/epidemiology/virology ; Hepatitis Viruses/isolation & purification ; Hepatitis, Viral, Human/*diagnosis/epidemiology/*virology ; Humans ; Korea ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo investigate the relationship and clinical significances of HBeAg status with serum HBV DNA loads, model for end-stage liver disease (MELD) scores in patients with acute-on-chronic hepatitis B liver failure during terminal phase.

METHODS120 fatal patients were enrolled. At three phases of 0 -14 d, 15-28 d and 29-90 d before death, they were detected serum HBeAg, HBV DNA loads order meanwhile MELD scores were calculated.

RESULTSIn 51 patients with HBeAg positive, HBV DNA levels were (5.25 +/- 1.99), (5.45 +/- 1.47) and (6.06 +/- 1.77) log10 copies/ml while MELD scores were (30.33 +/- 5.25), (26.36 +/- 6.43) and (20.13 +/- 6.47) respectively. In 69 patients with HBeAg negative,HBV DNA loads were (5.14 +/- 1.84), (5.49 +/- 1.75 ) and (4.62 +/- 1.65) log10 copies/ml while MELD scores were 32.38 +/- 9.95, 28.17 +/- 6.82 and 26.19 +/- 5.56 in sequence. Compared with the same phase between HBeAg-positive group and HBeAg-negative group, significant differences in both HBV DNA loads and MELD scores were found only at the phase of 29-90 d (P < 0.05). In multiple comparisons among three phases, regardless of the HBeAg status,there wasn't significant difference for HBV DNA loads (P > 0.05). But increasing MELD scores are associated with the disease exacerbation and significant differences were found (P < 0.05).

CONCLUSIONSTo initiate acute-on-chronic hepatitis B liver failure, serum HBV DNA loads of HBeAg-positive patients are higher than that of HBeAg-negative ones. Once ACLF has been initiated,sustained high HBV DNA loads may promote the disease worsened and be fatal regardless of the HBeAg status.

Adult ; Aged ; Aged, 80 and over ; DNA, Viral ; blood ; End Stage Liver Disease ; diagnosis ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; complications ; Humans ; Liver Failure, Acute ; etiology ; Male ; Middle Aged ; Severity of Illness Index ; Viral Load

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

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.
Adult ; Anemia, Hemolytic, Autoimmune/*diagnosis/drug therapy/etiology ; Anti-Inflammatory Agents/therapeutic use ; Cholestasis/*diagnosis/drug therapy/pathology ; Coinfection/*diagnosis ; Genotype ; Hepatitis A/complications/*diagnosis/genetics ; Hepatitis E/complications/*diagnosis/genetics ; Humans ; Immunoglobulin M/blood ; Liver/pathology/virology ; Male ; Prednisolone/therapeutic use ; RNA, Viral/blood

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

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

A retrospective review of 4,721 human immunodeficiency virus (HIV)-infected patients, followed at St. Luke's Roosevelt Hospital Center, New York City, was conducted from January 1, 2005 to December 31, 2009. HIV-Hepatitis B virus (HBV) co-infection rate was 218/4,721, 4.6%. Among co-infected patients, 19 patients (19/218, 8.7%) died; 13 patients (13/19, 68.4%) died from non-acquired immune deficiency syndrome (AIDS) defining including 2 patients with liver failure. More non-survivors (5 patients, 5/19, 26.3%) had liver cirrhosis than those who survived (8 patients, 8/199, 4.0%; P = 0.002). There were more patients with positive HBV e antigen (HBeAg) among non-survivors, (12 patients, 12/19, 63.2%) than among survivors (74 patients, 74/199, 37.2%; P = 0.047). HIV-HBV co-infection is associated with increased overall mortality. Therefore, use of dual active antiretrovirals, particularly, tenofovir (TDF) based regimen for optimal suppression of HIV-HBV and immune restoration with prevention of high risk behaviors may contribute to improved outcomes.
Adenine/analogs & derivatives/therapeutic use ; Adult ; Anti-HIV Agents/therapeutic use ; Coinfection/drug therapy/mortality ; Female ; HIV Infections/complications/*diagnosis/drug therapy ; Hepatitis B/complications/*diagnosis/drug therapy ; Hepatitis B e Antigens/blood ; Humans ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; New York City ; Organophosphonates/therapeutic use ; Retrospective Studies

OBJECTIVETo construct a noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B.

METHODS275 patients with chronic hepatitis B were divided into a training group (206 cases) and a validation group (69 cases). The constituent ratios of patients in the fibrosis stages S0-S3, fibrosis stage S4 (early cirrhosis) and active cirrhosis stage were calculated according to the liver biopsy results. 30 noninvasive variables, including age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), spleen-platelet ratio index (SRPI) and age-spleen-platelet ratio index (ASPRI), were analyzed by univariate analysis and multivariate logistic regression. Variables that were significantly different between patients with and without cirrhosis were used to construct a noninvasive prediction model, and the model was then tested in the validation group.

RESULTS(1) Of the 275 patients with chronic hepatitis B, 193 (70.2%) were in the fibrosis stages S0-S3, 42 (15.3%) in fibrosis stage S4, 40 (14.5%) in active cirrhosis stage. (2) There were 23 variables that are significantly different between patients with and without cirrhosis by univariate analysis. The 23 variables were further analyzed by multivariate logistic regression, and 4 independent factors, including international normalized ratio (INR), gamma glutamyltranspeptidase (GGT), ASPRI, hepatitis B e antigen (HBeAg) were used to construct a noninvasive prediction model. (3) By receiver operating characteristic curves (ROC) analysis, to discriminate patients in stages S0-S3 from patients in stage S4 and patients in active cirrhosis stage, the area under ROC (AUROC), cut-off value, sensitivity, specificity and accuracy of the model were 0.871, 0.458, 84.4%, 75.7%, and 79.7% respectively. To discriminate patients in active cirrhosis stage from patients in other stages, the AUROC, cut-off value, sensitivity, specificity and accuracy were 0.753, 0.526, 81.8%, 62.9%, and 67.4% respectively. There was no significant difference in AUROC between the training group and the validation group (P less than 0.05).

CONCLUSIONINR, GGT, ASPRI and HBeAg are associated with early cirrhosis and active cirrhosis. Our model can be used to predict early cirrhosis and active cirrhosis.

Adolescent ; Adult ; Biopsy ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; complications ; diagnosis ; Humans ; Liver ; pathology ; Liver Cirrhosis ; blood ; diagnosis ; etiology ; Male ; Middle Aged ; Models, Biological ; Platelet Count ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; Severity of Illness Index ; Young Adult ; gamma-Glutamyltransferase ; blood