BACKGROUND/AIMS: Although the only therapy of proven benefit for chronic hepatitis C is interferon alpha, the rate of sustained response after treatment with interferon is less than 25%. A 6-month course of combination therapy with interferon and ribavirin was associated with higher rate of long-term response than either interferon or ribavirin alone. Pilot studies suggested that combination of interferon and ursodeoxy-cholic acid (UDCA) resulted in higher biochemical response than interferon alone. We investigated the rates of end of treatment response(ETR) and sustained response(SR) of combination therapy of interferon e2a, ribavirin and UDCA and compared it with interferon a 2a alone. METHODS: Ninty-five naive patients with chronic hepatitis C who have been positive for anti-HCV by 3rd generation EIA and HCV RNA by RT-PCR and had elevated level of ALT over 6 months were included. They were assigned to three groups. Thirty seven patients in group 1 were treated with interferon a 2a (3MU thrice weekly) in combination with ribavirin (600mg/day) and UDCA (600mg/day) for 6 months. Twenty nine patients in group 2 were treated with the same dose of interferon a 2a alone for 6 months. Changes of ALT and HCV RNA were observed over 12 months (average 3029 mos) after the end of treatment in both groups. Twenty nine patients in group 3 were observed over 12 months without antiviral treatment. HCV genotypes were tested by Innop-Lipa in 24 patients in group 1. RESULTS: In group 1, not only ETR (68%) but also 12 month SR rate (54%) was significantly higher than group 2(31%, 21% respectively). There was no difference in relapse rate between two groups. The level of ALT became normalized and HCV RNA negative within 1 month after treatment in most responders in group l. Genotype 1b was associated with lower ETR and SR than non-lb, although not significant stastistically. CONCLUSION: Both the ETR and 12 month SR rate were significantly higher after combination treatment of interferon a 2a, ribavirin and UDCA than interferon e 2a alone in chronic hepatitis C. It is suggested that this combination is preferable to interferon alone in the treatment of naive patients with chronic hepatitis C.
Genotype ; Hepatitis C, Chronic* ; Hepatitis, Chronic* ; Humans ; Interferon-alpha* ; Interferons* ; Recurrence ; Ribavirin* ; RNA

No abstract available.

No abstract available.

BACKGROUND/AIMS: Lamivudine, an oral nucleoside analogue, effectively suppresses HBV replication and improves liver enzymes as well as liver histology. Long-term lamivudine therapy can induce the emergence of drug resistant HBV strains in some patients. The aim of this study was to evaluate the effects of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after HBeAg loss. METHODS: A total of 190 patients with HBeAg and HBV DNA positive showing abnormal serum levels of aminotransferases for at least 6 months received 100 mg of lamivudine once daily. The duration of lamivudine therapy was from 6-36 months (mean 14 months). Responder was defined as the ALT normalization with sustained suppression of HBV DNA and HBeAg loss. Therapy was to be stopped after HBeAg loss. Post-treatment monitoring continued for 1-21 months (mean 6 months). RESULTS: The cumulative HBeAg loss rates at 12 months and 18 months were 35% and 43%, respectively. Pretreatment serum HBeAg quantitation, and the duration of lamivudine therapy were independent predictive factors for HBeAg loss. The cumulative breakthrough rates at 18 and 24 months were 38% and 57%, respectively. Pretreatment HBV DNA level was the only predictable factor for breakthrough. Therapy was discontinued after HBeAg loss in 52 patients. Most episodes of relapse (15/16) occurred within 6 months after cessation of lamivudine. The cumulative relapse rates at 3 months and 6 months were 21% and 50%, respectively. A predictive factor for post-treatment relapse after HBeAg loss was the duration of lamivudine therapy. CONCLUSIONS: These results suggested the pretreatment quantitative HBeAg in serum and duration of lamivudine therapy are independent predictive factors for HBeAg loss. The HBeAg response of lamivudine-induced HBeAg loss was not durable after discontinuing therapy.
DNA ; Hepatitis B e Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Lamivudine* ; Liver Diseases* ; Liver* ; Recurrence ; Transaminases

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.
Acoustics ; Biomarkers ; Biopsy ; Diagnosis ; Diagnostic Tests, Routine* ; Elasticity Imaging Techniques ; Fibrosis ; Humans ; Liver Cirrhosis* ; Liver Diseases ; Liver*

Despite the introduction of hepatitis B virus (HBV) vaccine for over 20 years now, HBV infection remains an important health problem. Antiviral treatment of chronic hepatitis B has dramatically changed over the last decade. A variety of therapeutic options are now available for the treatment of chronic hepatitis B infection, including four nucleos (t) ide analogues (i.e lamivudine, adefovir, entecavir and clevudine), along with standard and pegylated interferon. Newer oral nucleos (t) ide analogues that include tenofovir, emtricitabine and telbivudine are soon likely to be approved in Korea. Given the wide array of choices and the complex nature of chronic hepatitis B (CHB) infection, selection of the appropriate therapeutic agent can be challenging for clinicians. To help guide clinicians in treating patients with CHB, the Korean Association for the Study of the Liver published a guideline in 2004, which was subsequently revised in 2007 on the basis of new developments in the field. This review includes the range of treatment options and criteria for determining when and how to most effectively intervene with antiviral therapy for chronically infected patients with HBV.
Adenine ; Antiviral Agents ; Deoxycytidine ; Drug Resistance ; Guanine ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Interferons ; Korea ; Lamivudine ; Liver ; Organophosphonates ; Thymidine ; Emtricitabine ; Tenofovir

Primary biliary cirrhosis (PBC) is characterized by histological findings of an immunoinflammatory destruction of small- and medium-sized bile ducts with progressive portal fibrosis, and the presence of anti-mitochondrial antibody (AMA) with a laboratory evidence of chronic cholestasis. The term "autoimmune cholangitis" (AIC) is used for a disease with the clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative AMA and positive anti-nuclear antibody (ANA) tests. Eight cases of AIC and ten cases of PBC were reviewed in order to determine whether there was any difference between two diseases in clinico-pathologic aspects. All of the patients were female and the mean ages of AIC and PBC patients were 48 and 47 years, respectively. ANA test was positive in six of ten PBC paients and their mean titer was lower than that of AIC patients. IgM level was significantly higher in PBC group than in AIC group. No significant difference was found between two groups with respect to biochemical and histopathological features. Since the only consistently distinguishing features between these two conditions are the autoantibody profile (AMA vs ANA) and immunoglobulin level (IgM), these two conditions might be part of a spectrum. PBC can be considered to be the same as AMA-positive AIC or alternatively AIC to be the same as AMA-negative PBC.
Bile Ducts ; Cholangitis* ; Cholestasis ; Female ; Fibrosis ; Humans ; Immunoglobulin M ; Immunoglobulins ; Liver Cirrhosis, Biliary*

BACKGROUND: The automated border detection(ABD) echocardiography has the ability of recognizing the endocardial-blood interface, and therefore, on-line estimation of the left ventricular(LV) volume every cardiac cycle. Compared with the off-line conventional 2-dimensional echocardiographic method that requires tracing the endocardial border manually, the ABDd system can be a convenient and objective method in the estimation of the LV volume and the ejection fraction(EF). The purpose of this study is to compare the LV volume and EF between the on-line ABD system and the convertional off-line echocardiographic method. METHODS: In two weeks, 83 adult patients older than 16 years of age were referred to our echocardiographic laboratory. Among these 83 patients, 64 patients who had a normal sinus rhythm were included to our study. Using the Hewlett-Packard SONOS 1500, a 2.5 MHz transducer was placed dat the cardiac apex. Patients with an apical 4 chamber view of the LV in which at least 75% of the endocardium was clearly seen were selected for study. On that view, the ABD system was turned on, and the reansmit power and the time-gain compensation controls were adjusted in order to approximate the automated border to the visually apparent endocardial surface. The LV end-diastolic volume(LVESV) and LV end-systolic volume(LVESV) were calculated by the method of disc. LVEDV, LVESV, and EF were displayed every cardiac cycle. Also the off-line estimation of the LV volume was performed by the method of disc, after manually tracing the endocardial border on the apical 4 chamber view. RESULTS: 44 patients(69%) of 64 patients had > or =75% of the LV endocardium visualized. LVEDV, LVESV, and Ef with the ABD system were highly correlated with those with the off-line, manually traced method(r=0.95, 0.8, respectively), but LVEDV and EF with toe ABD system were significantly less than those with the latter(p<0.01). The limits of agreement between tow methods(off-line, manually traced method-ABD system) were somewhat wide. Those of LVEDV, LVESV and EF were +22~-10ml(mean 6ml), +15~-14ml(mean 0.1ml), and +19~-12%(mean 3.8%), respectively. CONCLUSION: LVEDV,LVESV, and EF measurements by the ABD system and the off-line manually traced methods thve a strong correlation, The ABD system should habe clinical applications in setting, in which measurements of LV volume and Ef are important, But, the comparison with a more reliable method is necessary.
Adult ; Compensation and Redress ; Echocardiography* ; Endocardium ; Humans ; Toes ; Transducers

Hepatocellular carcinoma (HCC) is one of the most frequent and malignant diseases worldwide. Epidemiological studies have clearly demonstrated that chronic hepatitis B virus (HBV) infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes associated with malignant transformation have been identified. The predominant carcinogenic mechanisms of HBV-associated HCC are chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation. An important role is also played by the integration of HBV DNA into host cellular DNA, which disrupts or promotes the expression of cellular genes that are important in cell growth and differentiation. Especially, HBx protein is a transactivating protein that promotes cell growth, survival, and the development of HCC. Continued investigation of the mechanisms underlying hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver. Prevention of HBV infections and effective treatments for chronic hepatitis B are still needed for the global control of HBV-associated HCC. This review summarizes the current knowledge on the mechanisms involved in HBV-associated hepatocarcinogenesis.
Carcinoma, Hepatocellular* ; Cell Proliferation ; Cytokines ; DNA ; Fibrosis ; Hepatitis B virus ; Hepatitis B, Chronic ; Inflammation ; Liver ; Trans-Activators

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis.
Apoptosis/genetics ; Carcinoma, Hepatocellular/pathology/*virology ; Cell Cycle ; DNA Mismatch Repair ; Hepatitis B virus/genetics/*pathogenicity ; Hepatitis B, Chronic/*complications ; Humans ; Liver Neoplasms/pathology/*virology ; Neovascularization, Pathologic/genetics/virology ; Telomere/genetics ; Trans-Activators/*metabolism ; Transcription, Genetic