Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease.

Background: Interferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes. Methods: Ninety-nine CDH patients who received at least 6 months of interferon were selected. Maintained virologic response (MVR) was defined as hepatitis D virus RNA negative for 2 years after treatment discontinuation. Cumulative median interferon treatment duration was 24 months (range 6-126 months), with a median of 2 courses (range 1-8). Post-treatment median follow-up was 55 months (24-225 months). Results: Thirty-five patients achieved MVR. Cumulative probability of MVR increased with treatment duration and reached 50% at 5 years. Patients with MVR were less likely to die from liver disease or develop complications compared to patients without MVR (P = .032, P = .006, respectively). Cirrhosis at baseline and no response to therapy (odds ratio 16.1 and 5.23, respectively) predicted an adverse endpoint. Hepatitis B surface antigen clearance occurred in 37% of patients with MVR. Conclusion: Viral response to interferon increases with treatment duration and favorably affects the natural course of disease. Interferon treatment duration has to be individualized with careful post-treatment assessment.

Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome.

BACKGROUND & AIMS: Interferon is the only effective treatment for chronic hepatitis D virus (HDV) infection. No rules have been set for stopping treatment based on viral kinetics. We analyzed data from an international study of hepatitis D treatment to identify factors associated with outcomes of pegylated interferon treatment, with and without adefovir. METHODS: We analyzed data from the Hep-Net-International Delta Hepatitis Intervention Trial on 50 patients with compensated liver disease who tested positive for anti-HDV and HDV RNA. Subjects received pegylated interferon α 2a, with adefovir or placebo, or only adefovir, for 48 weeks. Twenty-four weeks after treatment ended, 41 patients were evaluated for levels of HDV RNA and DNA, liver enzymes, and hepatitis B surface antigen (HBsAg); liver biopsy specimens were analyzed for fibrosis. Response to therapy was defined as end-of-treatment response or post-treatment week 24 virologic response. In both cases virologic response was associated with undetectable HDV RNA levels. Patients with less than a 1 log decrease in HDV RNA at the end of treatment were considered null responders. RESULTS: Based on univariate and multivariate analysis, the level of HDV RNA at week 24 of treatment was associated more strongly with response to therapy than other factors analyzed. The level of HBsAg at week 24 of treatment was associated with a response to therapy only in univariate analysis. Lack of HDV RNA at week 24 of treatment, or end of treatment, identified responders with positive predicted values of 71% and 100%, respectively. At 24 weeks after treatment, a decrease in HDV RNA level of less than 1 log, combined with no decrease in HBsAg level, identified null responders with a positive predictive value of 83%. A decrease in HDV RNA level of more than 2 log at week 24 of treatment identified null responders with a negative predictive value of 95%. CONCLUSIONS: Based on an analysis of data from a large clinical trial, the level of HDV RNA at week 24 of treatment with pegylated interferon, with or without adefovir for 48 weeks, can identify patients who will test negative for HDV RNA 24 weeks after the end of treatment. This information can be used to help physicians manage patients receiving therapy for chronic hepatitis D.

Peginterferon plus adefovir versus either drug alone for hepatitis delta.

BACKGROUND: Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone, and adefovir dipivoxil alone. METHODS: We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 µg of peginterferon alfa-2a weekly plus 10 mg of adefovir daily, 29 received 180 µg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA, normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). RESULTS: The primary end point--normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48--was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P = 0.006 for the comparison of the first and third groups; P = 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log(10) IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P = 0.01 for the comparison of the first and second). CONCLUSIONS: Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection. (Current Controlled Trials number, ISRCTN83587695.).

Role of immunohistochemistry for hepatitis D and hepatitis B virus in hepatitis delta.

BACKGROUND & AIMS: Immunohistochemical assessment of liver tissue in chronic delta hepatitis (CDH) is underinvestigated. Aim of the study was (i) to assess variables associated with hepatitis D antigen (HDAg), hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) staining in the liver. METHODS: Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HBsAg, HBcAg and HDAg immunohistochemical (IHC) staining was semiquantitatively assessed. RESULTS: Hepatitis D antigen immunohistochemical staining displayed positive correlations with age and alanine aminotransferase (ALT) and negative correlations with serum HBsAg (P = 0.01 for all). HBsAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology (P < 0.001, P = 0.02 and P = 0.007 respectively). HBcAg staining was mainly nuclear and displayed negative correlations with serum HBsAg and histologic activity (P = 0.002 and P = 0.02 respectively). Pegylated IFN based treatment led to a decline of all IHC markers, however, these markers had no impact on treatment outcome. CONCLUSIONS: These data suggest an association of liver injury with HDAg expression in CDH whereas the negative correlation between HBcAg expression and liver injury and the overall nuclear localization of HBcAg suggest that HBcAg does not contribute to liver injury in CDH. HDV cases with high level of HBV replication, high serum HBsAg levels, HBeAg positivity, that are probably in the earlier stages of disease (low gamma-glutamyl transferase), had a more intense HBsAg staining profile. Overall, the data enforce the importance of HDAg and HBsAg in different phases of CDH infection.

HBeAg-positive hepatitis delta: virological patterns and clinical long-term outcome.

BACKGROUND AND AIMS: The presence of the hepatitis B virus (HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus (HDV). METHODS: We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti-HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline-MELD score. RESULTS: HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). CONCLUSIONS: HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV.

ATA Index: A novel score for predicting fibrosis stage in chronic viral hepatitis.

Background and Aim: This study was designed to predict the fibrosis stage with a clinical scoring system that may reduce the need for liver biopsy. Materials and Methods: The study cohort included the treatment of 430 chronic hepatitis B (CHB) and 170 chronic hepatitis C (CHC) of naive patients. The patients were divided into two groups as mild to moderate and severe fibrosis. After an index obtained in the study cohort, the index was tested in a validation cohort and compared with the FIB-4 Index. Results: The AUC of CHC index was found of 0.89 the sensitivity of 0.91 the specificity of 0.74, the positive predictive value (PPV) of 0.54 and the negative predictive value (NPV) of 0.96. The FIB-4 Index was applied to the CHC study cohort and the ATA Index Hepatitis C was found to be superior in terms of AUC (0.89-0.82), sensitivity (0.91-0.76) and NPV (0.96-0.86). The AUC of CHB Index was determined of 0.92, the sensitivity of 0.90, the specificity of 0.84, the PPV of 0.53 and the NPV of 0.98. Compared to the FIB-4 Index in CHB study cohort, the ATA Index Hepatitis B was predominant in terms of AUC (0.92-0.88), sensitivity (0.90-0.75), NPV (0.98-0.94) and PPV (0.53-0.49). Conclusion: ATA Indexes can predict the non-existence of severe fibrosis with an accuracy similar to FIB-4 Index and may reduce the need for liver biopsy.

Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis.

UNLABELLED: Abstract Background: Hepatitis delta virus (HDV) causes severe liver disease. AIMS: To investigate the quantitative HDV-RNA, HBsAg and hepatitis B virus (HBV)DNA levels in correlation to histological, biochemical and demographical parameters in patients with chronic HDV infection as similar data in a large series of HDV patients are missing. METHODS: Eighty HDV patients were recruited in Germany, Turkey and Greece; quantitative determination of HDV-RNA, HBsAg and HBV-DNA was performed by real-time polymerase chain reaction, the Architect HBsAg assay and Cobas TaqMan HBV test respectively. RESULTS: All patients were infected with HDV-genotype 1. Thirty-five patients (48%) had significant fibrosis (Ishak 3-4) and 15 (20.5%) had cirrhosis. HDV viraemia ranged from 1.1 x 10(3) to 8.4 x 10(7) copies/ml with 60% of patients showing HDV-RNA levels above 10(5) copies/ml accompanied by low HBV viraemia (<10(5) copies/ml). However, HDV-RNA and HBV-DNA levels showed no direct inverse correlation. HDV-RNA correlated positively with HBsAg and negatively with age. HBsAg correlated negatively with age and positively with histological grading. Only gamma-glutamyltranspeptidase was independently associated with cirrhosis (P=0.032), while no biochemical parameter was associated with grading. CONCLUSIONS: (i) HBsAg levels correlated with HDV viraemia in chronic HDV. (ii) Biochemical parameters did not accurately indicate the stage and grade of liver disease in chronic HDV and thus liver biopsy seems to remain the major tool for the evaluation of delta hepatitis patients.

The characteristics and clinical outcome of drug-induced liver injury: a single-center experience.

BACKGROUND AND GOALS: The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. STUDY: Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. RESULTS: During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. CONCLUSIONS: DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.

Endoscopic management of biliary parasitic diseases.

UNLABELLED: AIM/MATERIALS AND METHODS: Between January 2000 and June 2007, 3,548 endoscopic retrograde cholangiopancreatography (ERCP) were performed for extrahepatic cholestasis, cholangitis, and choledocholithiasis. The results of ERCPs were evaluated retrospectively and examined carefully to investigate the management and endoscopic therapy of biliary parasites. RESULTS: Of the 3,548 patients who underwent ERCP, 24 (0.66%) were found to have biliary parasitosis. The mean age of the biliary parasitosis patients (16 women) was 48.6 (15-77) years. Of these 24 cases, 16 patients had hydatid cystic disease (eight with partial obstruction of the biliary tract, and eight with ruptured cysts), four patients had Fasciola hepatica, and four patients had Ascaris lumbricoides infestation. Endoscopic sphincterotomy was performed, after which the choledochus was examined carefully by balloon catheter and basket procedure. CONCLUSION: The ERCP procedure is very useful in the therapy of biliary parasitic infestations.

Pegylated interferon-alpha plus taurine in treatment of rat liver fibrosis.

AIM: To investigate the antifibrotic effects of peginterferon-alpha 2b and taurine on oxidative stress markers and hepatocellular apoptosis. METHODS: Sixty rats with CCl4-induced liver fibrosis were divided into 4 groups (n=15). Group 1 was left for spontaneous recovery (SR). Groups 2-4 received peginterferon-alpha 2b, taurine, and their combination, respectively, for four weeks. Histological fibrosis scores, histomorphometric analysis, tissue hydroxyproline, tissue MDA, GPx and SOD activities were determined. Activated stellate cells and hepatocellular apoptosis were also evaluated. RESULTS: The degree of fibrosis decreased in all treatment groups compared to spontaneous recovery group. Taurine alone and in combination with peginterferon-alpha 2b reduced oxidative stress markers, but peginterferon-alpha 2b alone did not. Apoptotic hepatocytes and activated stellate cells were higher in groups 2-4 than in group 1. Combined taurine and peginterferon-alpha 2b further reduced fibrosis and increased activated stellate cell apoptosis, but could not improve oxidative stress more than taurine alone. CONCLUSION: Peginterferon-alpha 2b exerts anti-fibrotic effects on rat liver fibrosis. It seems ineffective against oxidative stress in vivo. Peginterferon-alpha 2b in combination with taurine seems to be an antifibrotic strategy.

Lamivudine treatment in HBeAg-negative chronic hepatitis B patients with low level viraemia.

BACKGROUND: Our aim was to determine the short-term natural course of viraemia and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B patients with a persistently low hepatitis B virus (HBV)-DNA level. METHODS: A total of 55 patients were included. Group 1 consisted of 37 patients with low-level viraemia and high serum alanine aminotransferase (ALT) levels and further randomized to two groups: group 1a (n=19) patients received 1 year of lamivudine therapy and group 1b (n=18) patients were untreated controls. Group 2 consisted of 18 inactive carriers who were followed as controls of untreated low viraemic chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time polymerase chain reaction assay. RESULTS: A female predominance in group 2 was observed while males were predominant in group 1. Mean age and baseline HBV-DNA levels did not differ between group 1 and 2 patients while group 1 patients had a higher histological score (P<0.01). Of group 1a patients, 44% had complete ALT normalization at end of treatment, whereas 21% untreated group 1b patients had normal ALT at the end of the follow-up. No change in histological activity was observed in group 1a patients at the end of treatment. HBV-DNA levels did not significantly change from baseline to end-of-treatment/observation period in patient groups. The viraemia course was not different across the groups. CONCLUSIONS: Low viraemic HBeAg-negative patients with high ALT present with minimal/mild histological activity. Inactive carriers cannot be differentiated from low viraemic patients with high ALT based on HBV DNA determination. Although lamivudine treatment can be effective in some cases, observation rather than a prompt treatment attempt seems to be more logical because of mild histological changes and low response rate to treatment in these patients.

Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis.

OBJECTIVE: Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT. PATIENTS AND METHODS: A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism. RESULTS: Aetiologies and Child-Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups. CONCLUSIONS: Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.

Peroxisome proliferator-activated receptor alpha L162V polymorphism in nonalcoholic steatohepatitis and genotype 1 hepatitis C virus-related liver steatosis.

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) plays important roles in lipid metabolism. A recently discovered L162V polymorphism of the PPARalpha gene is associated with enhanced transcriptional activity. In this study, the frequency of L162V was investigated in nonalcoholic steatohepatitis (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis. METHODS: Seventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without steatosis) and 119 healthy controls were included. L162V polymorphism of the PPARalpha gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: PCR and RFLP analysis of the related gene segment was successful in 93%, 96%, and 100% of NASH and HCV-infected patients and controls, respectively. The frequency of the L162V polymorphism was similar in the NASH and HCV-infected patients and controls (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this polymorphism was observed in HCV-infected patients with or without significant liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. CONCLUSIONS: Neither NASH nor genotype 1 HCV-related liver steatosis seems to be associated with the PPARalpha L162V polymorphism. This polymorphism may have no association with the presence of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH and HCV-infected patients.

P21 expression and its relation to disease activity and hepatocyte proliferation in chronic hepatitis B virus infection.

BACKGROUND/AIMS: P21 protein, a cell cycle regulatory protein expressed in the liver, acts as an inhibitor of cyclin dependent kinase and prevents progression of the cell cycle. In the present study, our aim was to investigate the relationships between P21 protein expression and hepatocyte proliferation, hepatitis B virus replication, and hepatitis activity. METHODS: A total of 66 patients with chronic hepatitis B without cirrhosis were included in the study. These patients were evaluated in three different groups according to the degree of viral replication and the disease activity. Group 1: HBeAg-positive patients with active liver disease and with viral replication, group 2: HBeAg-negative patients with active liver disease and with viral replication, and group 3: HBeAg-negative inactive carriers. P21 and proliferating cell nuclear antigen were immunohistochemically stained and a labeling index was calculated for each protein. RESULTS: A total of 32 (48.4%) patients were positive for nuclear P21 expression. All three groups had a similar P21 index. proliferating cell nuclear antigen-labeling index, hepatit B virus DNA levels, ALT levels, and HAI scores were not different in patients with and without P21 staining. Spearman's correlation analysis found no correlation between P21 staining and ALT and hepatit B virus DNA levels, HAI score and proliferating cell nuclear antigen-labeling index. CONCLUSIONS: These results suggest that the pattern of P21 expression is not associated with histological activity, hepatocyte proliferation and virus replication in patients with well-compensated chronic hepatitis B.

Utility of endoscopy for diagnosis of barrett in a non-Western society: endoscopic and histopathologic correlation.

Barrett esophagus is metaplastic transformation of esophageal squamous epithelium to columnar cells. A total of 1370 patients who had undergone upper endoscopy because of dyspeptic complaints were enrolled in the study. Age, sex, alcohol and smoking habits, body mass index, type and duration of symptoms (heartburn, epigastric pain, nausea, vomiting), and use of proton pump inhibitors were evaluated in all patients and recorded on standardized forms. Patients were grouped as normal esophagogastric junction, long-segment Barrett esophagus, and short-segment Barrett. Biopsies were taken from at least 6 points and examined histopathologically. Of the 1370 patients involved in the study, 748 (54.6%) were female and 622 (45.4%) were male. Mean age was 47.2 ± 15.30 years. Short-segment Barrett esophagus was detected in 16 patients, and long-segment Barrett was detected in 11 patients. Although Barrett esophagus was detected in 11 cases that were suspected to have Barrett during endoscopy, histopathology was negative in all cases that were not suspected to have Barrett. Barrett esophagus prevalence was significantly higher in people who used alcohol and tobacco and who had hiatal hernia. Although Barrett esophagus was detected in 40% of cases that were suspected to have Barrett during endoscopy, histopathology was negative in all cases that were not suspected to have Barrett. Barrett was detected in 40.7% of cases that were suspected to have Barrett during endoscopy; histopathology was negative in all cases that were not suspected to have Barrett. Senstivity of endoscopy is questionable in detection of short-segment Barrett.

Oral ganciclovir for treatment of lamivudine-resistant hepatitis B virus infection: a pilot study.

Although liver disease seems to be stable in most patients who are infected with lamivudine-resistant mutant hepatitis B virus (HBV) in the short term, it may progress to more-advanced disease in some patients. In our pilot study, we investigated the efficacy of oral ganciclovir for the treatment of lamivudine-resistant HBV infection. Six patients infected with lamivudine-resistant HBV (3 patients had decompensated cirrhosis and 3 had chronic active hepatitis without cirrhosis) were included. Ganciclovir was administered at a dosage of 3 g daily for 6 months. Four of 6 patients completed the 6-month treatment period. Two patients with cirrhosis completed only 2 months of ganciclovir treatment because they died of cirrhosis complications. None of the patients had a > or =2-log(10) reduction of HBV DNA and complete alanine aminotransferase normalization at the end of their treatment regimens. In conclusion, 6 months of ganciclovir treatment is not effective for suppression of lamivudine-resistant HBV infection.

The role of HBeAg seroconversion in acute exacerbation of liver disease with termination of hepatitis B and D virus infection in a chronic hepatitis D patient during alpha-interferon therapy.

We report a severe flare-up in a chronic hepatitis patient due to dual infection with hepatitis B and D viruses during alpha-interferon therapy. Pre-treatment, the patient had detectable levels of both viruses. After 9 months of therapy, an alanine aminotransferase flare with acute hepatic decompensation was detected. Alpha-interferon was discontinued and lamivudine (100 mg once daily) was started, after which the patient reversed slowly. Hepatitis B early antigen (HBeAg) seroconversion with hepatitis B virus-DNA clearance was observed 1 month after the flare; 15 months later, the patient had persistently normal alanine aminotransferase levels with negative results for both serum hepatitis B virus-DNA and hepatitis D virus-RNA. In conclusion, liver disease may be exacerbated during interferon therapy in patients with chronic hepatitis D who are also positive for hepatitis B surface antigen (HBsAg) and HBeAg. Therefore, extra care in monitoring should be considered and strict follow-up is recommended, since clearance of hepatitis D may occur after HBeAg seroconversion in coinfected patients. Lamivudine may be administered early in hepatitis D-RNA/HBsAg-positive patients at high risk of liver failure once a severe flare-up occurs during interferon therapy.

Percutaneous transhepatic venoplasty: an alternative treatment for Budd-Chiari syndrome.

BACKGROUND/AIMS: In patients with Budd-Chiari syndrome due to short segment hepatic vein stenosis where percutaenous transluminal venoplasty is not successful, percutaneous transhepatic balloon venoplasty may be a valid treatment option. The aim of this prospective study was to evaluate the effects of this procedure for the treatment of patients with Budd-Chiari syndrome, in whom transluminal cannulation was unsuccessful. METHODS: Ten patients with short segment occlusion of the hepatic veins were treated by percutaneous transhepatic balloon venoplasty between January 1997 and January 2000. The median follow-up period of these patients was 20 months (2-33 months). RESULTS: The procedure was unsuccessful in two patients. Eight patients (five men, three women) with a median age of 28 (range, 15-61) years were treated by percutaneous transhepatic balloon venoplasty and in seven of them, clinical symptoms including abdominal distension and ascites, resolved completely. Long term anticoagulation therapy was not given to the patients. One patient with advanced stage liver disease died of variceal bleeding two months after the procedure. During follow-up, symptomatic reocclusion requiring dilatation occurred in three patients. CONCLUSIONS: Percutaneous transhepatic balloon venoplasty is an alternative treatment option for selected patients with Budd-Chiari syndrome when transluminal cannulation of the hepatic veins is not possible. Long term anticoagulation therapy seems to be necessary in these patients.

The mutations in ISDR of NS5A gene are not associated with response to interferon treatment in Turkish patients with chronic hepatitis C virus genotype 1b infection.

BACKGROUND/AIMS: A significant association between variations in amino acid sequences resides between 2209-2248 nucleotides of HCV non-structural 5A (NS5A) gene, and response to interferon treatment has been proposed. The aim of this study was to determine whether the amino acid sequence changes in ISDR could be correlated to response to alpha interferon treatment in Turkish patients infected with HCV genotypes 1b and 1a. METHODS: Thirty-nine patients with chronic C virus infection (35 and 4 patients with genotype 1b and 1a, respectively), receiving 3x3-5 MU of interferon a-2b for six months were included in the study. Following PCR amplification of the region from pre-treatment serum samples, the products were directly sequenced. The amino acid sequence of NS5A was compared with the published sequence for HCV-J (AA 2209-2248). Mutant type was defined as three or more amino acid mutations, and intermediate type as 1-3 amino acids in this region. Otherwise, they were defined as the wild type (no amino acid mutations). HCV RNA serum viremia levels were analyzed by branched DNA assay. RESULTS: Eighteen patients were responders (R; 46%), whereas 21 patients were non-responders (NR; 54%). Amino acid changes in both R and NR groups did not show significant difference. Intermediate or wild type strains were detected in both groups. CONCLUSIONS: In this study, we could not determine a significant association between number of amino acid changes in NS5A2209-2248 and response to interferon treatment. In the majority of the patients, it seems that amino acid sequences in this region are well conserved.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis.

INTRODUCTION/AIM: Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. METHOD: The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. RESULTS: Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). CONCLUSION: Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis.