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.

Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation.

BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.

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.

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.

Factor V Leiden, prothrombin G20210A and MTHFR gene mutations in inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) gene mutations in IBD patients followed in our outpatient clinic. METHODS: Thirty-four patients with ulcerative colitis and 28 patients with Crohn's disease and 80 healthy controls were included in the study. No patient had a history of previous thromboembolism. Factor V Leiden, prothrombin G20210A and MTHFR gene mutations were studied. RESULTS: Heterozygote factor V Leiden mutation was found in five (6.25%) control patients and in two (3.2%) IBD patients. Heterozygote MTHFR mutation was obtained in seven (11.3%) IBD patients and in five (6.25%) controls. Heterozygote prothrombin G20210A mutation was found in two (2.5%) and homozygote MTHFR mutation in one (1.25%) control patient. There was no statistical difference between the IBD group and healthy controls. CONCLUSIONS: Genetic mutations that could increase the thrombosis risk were not found to be different in IBD versus the normal population in our study.

Screening for hemochromatosis in Turkey.

In this study we screened 3060 consecutive blood donors for an unbound iron-binding capacity level of <28 microM and then performed HFE mutation analysis in these subjects. Sixty-five of the 75 subjects with a low initial unbound iron-binding capacity (all had normal ferritin levels) came back and only 5 (8%) had a low fasting unbound iron-binding capacity. Mutational analysis revealed H63D heterozygosity in two of five subjects. Four of five subjects had liver biopsy indication and none had increased liver iron. HFE genotyping of 60 subjects with a low initial but normal fasting unbound iron-binding capacity revealed heterozygote H63D in seven (11.6%). No allelic variant of position 282 or 63 was found in three previously diagnosed patients with hereditary hemochromatosis. In conclusion, full phenotypic expression of hereditary hemochromatosis is very rare in Turkey. The absence of HFE mutations in three patients with hereditary hemochromatosis suggests that hereditary hemochromatosis in Turkey occurs without common HFE mutations.