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Biomedical subjects

Hakan Bozkaya

Publications and source records attributed to Hakan Bozkaya.

At least 19 recordsLinked to original sources
PubMed2006

Antituberculous therapy-induced fulminant hepatic failure: successful treatment with liver transplantation and nonstandard antituberculous therapy.

Standard antituberculous therapy including isoniazid, rifampin, ethambutol, and pyrazinamide is widely used for the treatment of active tuberculosis. Its most important side effect is hepatotoxicity, ranging from asymptomatic transaminitis to fulminant hepatic failure. A 19-year-old woman was admitted to our unit due to jaundice and unconsciousness. According to her past medical history, she was diagnosed as having extrapulmonary tuberculosis and had been prescribed standard antituberculous therapy. The patient became icteric and unconscious on the fourth day after therapy initiation. She was diagnosed with drug-induced acute fulminant hepatic failure and underwent living-related liver transplantation. Nonhepatotoxic antituberculous therapy (cycloserine, ciprofloxacin, streptomycin, and ethambutol) and low-dose immunosuppressive therapy were started after transplantation. Currently the patient is very well with normal graft function 42 months after transplantation. Here we report a case of a patient with acute fulminant hepatic failure caused by isoniazid, rifampicin, or both, who was successfully treated with living-related liver transplantation and a relatively less hepatotoxic antituberculous therapy. In conclusion, liver transplantation is a feasible therapy for individuals with standard antituberculous therapy-induced hepatic failure. Nonhepatotoxic antituberculous therapy may achieve control of active tuberculosis in such individuals after transplantation.

Adult↗
PubMed2006

Long-term prognosis of nonalcoholic fatty liver disease: is pharmacological therapy actually necessary?

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver injury, ranging from steatosis and steatohepatitis to cirrhosis. Reasons for the different natural course in individuals with NAFLD are still unclear. The aim of this study was to describe the natural course of disease in individuals with NAFLD who did not receive pharmacological therapy. METHODS: A total of 27 individuals with NAFLD (male/female ratio: 10/17, mean age 49.7 years) were prospectively enrolled. Management after diagnosis consisted of establishment of an appropriate diet and exercise (walking and jogging) program, treatment of associated metabolic conditions such as diabetes and dyslipidemia, and discontinuation of potentially hepatotoxic drugs if the patient was taking these. Liver tests were performed at diagnosis and at 3-month intervals during the follow-up period. Mean follow-up period was 43.3 months (range 36-49 months). RESULTS: From baseline to the end of the follow-up period, although there was no significant difference observed in terms of the mean body mass index, serum aminotransferase levels significantly improved (48.8+/-29.9 U/L to 31.6+/-16.0 U/L for aspartate aminotransferase [AST] and 66.3+/-38.3 U/L to 39.6+/-22.9 U/L for alanine aminotransferase [ALT]; P<0.05). No significant differences in platelet counts, serum albumin level or prothrombin time were observed (P>0.05). No patient developed signs of advanced liver disease during the follow-up period. CONCLUSION: A treatment strategy comprising diet, exercise and management of associated metabolic conditions is associated with improvement in aminotransferases among patients with NAFLD. Further investigation is needed to examine the long-term efficacy of this approach on liver histology and clinical outcomes.

Alanine Transaminase↗
PubMed2006

Hepatitis B core antigen expression pattern reflects the response to anti-viral treatment.

BACKGROUND: In hepatitis B early antigen (HBeAg)-negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B. METHODS: A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV-DNA levels were measured by a hybrid capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV-DNA negativity. RESULTS: At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non-responders. Age, sex, ALT, HBV-DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non-responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non-responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non-responders had positive HBcAg staining. CONCLUSION: Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (-) patients. The PCNA determination does not predict treatment response.

Adult↗
PubMed2005

Fatigue of cholestasis and the serotoninergic neurotransmitter system in the rat.

Fatigue associated with cholestasis may impair health-related quality of life. The pathogenesis of this symptom is largely unknown, but it has been suggested that central serotoninergic neurotransmission may be implicated and that serotonin 1A receptor agonists may yield improvement. The aim of this study was to study the central serotoninergic system, specifically the serotonin (5-HT)(1A) receptor-mediated pathway of serotoninergic neurotransmission, in a bile duct resection rat model of cholestasis. Fatigue was assessed in the forced swim test in sham and bile duct-resected rats. The serotonin behavioral syndrome, which includes hyperlocomotion, was assessed in both groups of rats after escalating doses of the 5-HT(1A) receptor agonist 8-hydroxy(di-n-propylamine)tetralin (8-OH DPAT). 5-HT(1A) and 5-HT(2) receptor densities were explored in four brain regions using a receptor-binding assay. Extracellular 5-HT and 5-hydroxyindoleacetic acid were measured via in vivo brain dialysis. Bile duct-resected rats spent more time floating in the forced swim test, and 8-OH DPAT decreased floating time in cholestatic rats (P < .01). Dose-response curves created with 8-OH DPAT for the serotonin behavioral syndrome were similar in bile duct-resected and sham-operated rats. 5-HT(1A) and 5-HT(2) receptor densities in most brain regions and extracellular serotonin levels were similar in both groups of rats. In conclusion, 5-HT(1A) receptor agonist-induced amelioration of fatigue in cholestatic rats may be nonspecific and not linked to reversal of the pathophysiology of fatigue associated with cholestasis; however, these data do not exclude a potential role of the central serotoninergic system in the evolution of fatigue.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2005

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.

Adult↗
PubMed2005

Sarcoidosis caused by interferon therapy.

Interferon alpha (IFN-alpha) is an immunomodulator that is used as an antiviral agent in active chronic viral hepatitis C. IFN therapy can cause an induction or exacerbation of sarcoidosis. Although several reports in the gastroenterology literature have suggested an association between IFN therapy and sarcoidosis, this association has rarely been described elsewhere. A 47-year-old woman developed sarcoidosis after cessation of treatment with IFN and ribavirin for chronic hepatitis C. Her sarcoidosis showed liver, pulmonary and skin involvement. She continues to be monitored regularly in the Department of Pulmonary Diseases without steroid therapy. Her sarcoidosis improved spontaneously. We conclude that patients should be monitored for sarcoidosis during and after IFN therapy.

Antiviral Agents↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

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.

Adolescent↗
PubMed2004

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.

Adult↗
PubMed2004

Ligand- and species-dependent activation of PPARalpha.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is mainly expressed in liver and involved in lipid metabolism. Oxidation of certain fatty acids in peroxisomes is under PPARalpha control. A wide variety of lipid molecules activate PPARalpha as well as the fibric acid derivative clofibrate. In the present study, we evaluated the differential activation of PPARalpha with several agonist ligands through its expression and DNA binding in both rat (McA-RH7777) and human (HepG2) hepatoma cell lines. In McA-RH7777 cells, clofibrate alone mediated a higher induction of PPARalpha expression than linoleic acid. In contrast, linoleic acid was the most effective ligand in HepG2 cells and treatment with clofibrate plus linoleic acid did not further increase PPARalpha expression. PPRE-binding activity of PPARalpha in ligand-treated cells was also increased in a parallel manner. We suggest that ligand-induced PPARalpha activation might give rise to differential species-dependent responses.

Animals↗
PubMed2004

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.

Adult↗
PubMed2004

Lichen planus and HCV infection in Turkish patients.

BACKGROUND/AIMS: A relation between hepatitis C virus (HCV) infection with lichen planus (LP) has been reported in the literature but remains controversial. To find out the prevalence of HVC infection among patients with LP. METHODS: Forty-one cases of LP diagnosed at the Dermatology Clinic of our hospital between March 1995 and May 1996 were evaluated (22 men and 19 women; mean age 41.6 years). They were screened for the presence of HBsAg, anti HBs, and anti-HCV by ELISA and HCV-RNA by nested polymerase chain reaction (PCR). Blood donors registered in Ankara University Ibni Sina Hospital Blood Bank were used as a control group. RESULTS: Of the 41 LP patients, 2 (4.8%) had anti-HCV positivity together with HCV-RNA positivity. Twelve patients (29.2%) had anti-HBs and 3 patients (7.3%) had HBsAg positivity. In blood donors, anti-HCV positivity prevalence was 2.5%. CONCLUSIONS: The results of this study suggest that no relationship exists between hepatitis C virus infection and lichen planus among Turkish patients.

Adult↗
PubMed2004

Contrast-enhanced MR angiography of benign regenerative nodules following TIPS shunt procedure in Budd-Chiari syndrome.

In this report we describe the magnetic resonance (MR) angiographic features of benign hepatic nodules that developed in a patient with Budd-Chiari syndrome, and present the distinguishing features of benign regenerative nodules from hepatocellular cancer. In a 27-year-old woman with chronic Budd-Chiari syndrome, previously non-existing benign nodules developed in the liver parenchyma during the 10-month period following transjugular intrahepatic portosystemic (TIPS) shunt placement. The liver had been examined with gray-scale and Doppler sonography in addition to the MR imaging and MR angiography. On MR angiography, more hepatic nodules became visible in the portal venous phase compared to that of the arterial phase. Delayed washout of contrast medium in nodules was considered to be due to stasis in hepatic sinusoids. Hypervascularization, appearance after portosystemic shunt creation, multiplicity, small size ( <=2 cm in diameter in our patient), presence of peripheral rim, and high signal intensity on T1-weighted images are important imaging features of benign hepatic nodules that develop in patients with Budd-Chiari syndrome.

Adult↗
PubMed2003

Interferon-alpha2b induction treatment with or without ribavirin in chronic hepatitis C: a multicenter, randomized, controlled trial.

We aimed to compare the efficacy of interferon-alpha2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 +/- 9, range: 21-70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000-1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P > 0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.), resulting in a sustained virologic response (SVR) rate of 17% in the placebo and 39% in the ribavirin group (P = 0.005.) In conclusion, IFN induction treatment in combination with ribavirin is superior to IFN induction treatment alone in genotype 1 patients, and the SVR rate of 39% is encouraging.

Antiviral Agents↗
PubMed2003

Nuclear localization of hepatitis B core antigen and its relations to liver injury, hepatocyte proliferation, and viral load.

GOALS: The aim of this study was to determine the factor(s) independently affecting the HBcAg expression pattern in HBV-infected livers. BACKGROUND: Subcellular localization of HBcAg have been found to be related to the activity of liver disease, hepatocyte proliferation rate and the level of HBV replication. STUDY A total of 98 patients with biopsy proven chronic hepatitis B were included. HBcAg and proliferative cell nuclear antigen (PCNA) were immunohistochemically detected. HBcAg expression and its relationship with histologic activity index, ALT levels, PCNA score and HBV DNA levels were investigated. RESULTS: Forty-three (44%) patients were positive for HBcAg staining, with most of them (37 patients) having nuclear localization. Forty-seven percent of patients with detectable HBV DNA had nuclear staining while none of the HBV DNA negative patients had nuclear staining ( < 0.0005). Patients with positive nuclear staining had lower HAI (<8) and a lower PCNA score (<353/1,000 cell) than those with negative staining (62% vs. 39% and 90% vs. 66%, respectively, P< 0.05). In multivariate analysis, both high HBV DNA level and low HAI ( P< 0.0005 and P< 0.05, respectively) but not PCNA score, were independently associated with nuclear staining of HBcAg. CONCLUSIONS: Our results suggest that viral load and the severity of liver damage but not the rate of hepatocyte proliferation independently affects the HBcAg expression pattern.

Adult↗
PubMed2003

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.

Acute Disease↗