A Pilot Comparative Study Between Serological and Genetic Investigations in Relationship to Clinical Outcomes on Patients with Cystic Echinococcosis.

The aim of this study was to investigate whether Enzyme-Linked Immunosorbent Assays (ELISA) and Western Blotting (WB) methods could contribute to the assessment of clinical outcomes in genotype-defined cystic echinococcosis (CE) patients. Twenty-nine human isolates and blood samples have been taken from patients who underwent surgery or percutaneous aspiration (PAIR) for therapeutic purposes at Ege University and Manisa Celal Bayar University Hospitals. All sera of patients were screened for the presence of E. granulosus IgG antibodies using in-house approved ELISA and WB methods. According to the ELISA results, five patients had high, thirteen patients had medium and eight patients had low specific antibody level response which ranged 1/640 -1/5000. Despite confirmed WB positivity three patients were found to be negative by ELISA. Immunoblot analysis of EgAg showed many protein bands with size of 8, 12, 20, 22, 24, 36, 75 and 90 kDa. Among of them, 8 - 12 kDa bands (90 %), 20 - 22 kDa and 36 kDa bands presented strong reactivity against human serum specimens. No serum samples from healthy control reacted with EgAg. Phylogenetic analysis of resulting COX1 and NAD1sequences has revealed that all patients in our study were infected with the E. granulosus G1-G3 genotype. There was no consistent correlation between results of ELISA and WB, the number or size of cysts and genotype. Our study brings a unique contribution in terms of relationship between serological investigation, disease genotypes and clinical outcomes.

Endovascular Repair and Adjunctive Immunosuppressive Therapy of Aortic Involvement in Behçet's Disease.

OBJECTIVES: Aortic aneurysm is a serious problem in Behçet's disease, but open surgical therapy carries the risk of recurrent pseudoaneurysm. Here the outcomes of endovascular repair and adjunctive immunosuppressive therapy for aortic disease in Behçet's disease are presented. MATERIALS: This was a retrospective study. Between 2002 and 2012, nine patients with Behçet's disease (8 male, median age 41 years, range 33-60 years) were treated by endovascular stent grafting for abdominal or thoraco-abdominal aortic pseudoaneurysm. METHODS: Computed tomography angiography revealed infrarenal pseudoaneurysm in six (66.6%) patients and suprarenal pseudoaneurysm in three (33.3%). Patients received immunosuppressive therapy with oral prednisolone (60 mg/day) and cyclophosphamide (200 mg/day) for 2 weeks or more before the procedure, and intravenous hydrocortisone (200 mg/day) combined with cyclophosphamide (200 mg/day) for 3 days after the procedure. Thereafter, oral immunosuppressive therapy was continued for 2 years. RESULTS: A straight tube graft was implanted in seven patients and a bifurcated graft in two patients. Two stage procedures (debranching before endovascular therapy) were performed in three patients for thoraco-abdominal aortic pseudoaneurysms. Stent grafting was successful in all patients, without any peri-operative complications. However, two patients needed abdominal exploration later: one for seroma around the graft and the other for a fistula between the duodenum and the graft. No recurrence of aneurysm was observed during a mean follow up of 40 ± 16 months. One patient died in the 15th month from a non-vascular cause. CONCLUSIONS: Endovascular stent graft implantation and adjunctive immunosuppressive therapy seems to be safe and effective in the treatment of aortic involvement in Behçet's disease, but this approach needs further evaluation.

Tumour necrosis factor-alpha, interleukin-10, interferon-gamma and vitamin D receptor gene polymorphisms in patients with chronic hepatitis delta.

No data exist to assess certain polymorphisms that have a potential effect on the immune response in patients with chronic hepatitis delta (CHD). The aim of this study was to investigate polymorphisms in 6 polymorphic sites: IL-10 -1082 (rs1800896), IL-10 -627 (rs1800872), IFN-γ +874 (rs62559044), TNF-α -308 (rs1800629), vitamin D receptor (VDR) FokI (rs2228570) and VDR TaqI (rs731236). The genotypes of 67 patients with CHD and 119 patients with chronic hepatitis B (CHB) were compared. In addition, 56 individuals with resolved hepatitis B virus (HBV) infection were used as a control group for patients with CHB. Polymorphisms in TNF-α, IL-10, and VDR genes were analysed using polymerase chain reaction/restriction fragment length polymorphism methods. The IFN-γ gene polymorphism was detected by allele-specific polymerase chain reaction (PCR). Patients with CDH were more likely to have advanced liver disease compared with patients with CHB (P < 0.0001). IL-10 -1082 and VDR TaqI polymorphisms showed significant differences between patients with CHD and CHB. The high secretory IL-10 -1082 genotype GG was less frequent in CHD compared with patients with CHB and resolved HBV (17.7%, 37.4% and 47.1%, respectively (P < 0.05 for CHD vs CHB and resolved HBV). The frequency of the high secretory VDR TaqI TT genotype was 86.6% in patients with CHD, 62.7% in patients with CHB and 62.5% in resolved HBV individuals (CHD vs CHB: P < 0.05). None of the polymorphisms analysed had an effect on HBV persistence. IL-10 -1082 and VDR TaqI polymorphisms may contribute to the more severe liver disease associated with CHD compared with CHB.

The effect of chronic pelvic pain scoring on pre-term delivery rate.

A total of 57 pregnant women, who were admitted to the outpatient clinic having high visual analogue scale (VAS) and a history of chronic pelvic pain before pregnancy, were evaluated with the international pelvic pain assessment form (IPPAF). Gynaecological disorders, pain at ovulation, dysmenorrhoea, level of cramps with period and suspicion of endometriosis were determined to be higher in the pre-term group (p < 0.05). Regarding urological disorders, pain when the bladder was full, pain with urination, a positive answer to the question, 'Does your urgency bother you?' and suspicion of interstitial cystitis were also determined to be higher in the pre-term group (p < 0.05). Thus, the total IPPAF scores were significantly higher in the pre-term group (p < 0.05). The pregnant women with a higher total IPPAF score before pregnancy may thus have a higher probability of pre-term labour.

The effects of hormone therapy on ischemia modified albumin and soluble CD40 ligand levels in obese surgical menopausal women.

PURPOSE: To determine the effects of hormone therapy (HT) on ischemia modified albumin (IMA) and soluble (s)CD40 ligand in obese surgical menopausal women. MATERIALS AND METHODS: A total of 52 obese surgical menopausal women with a body mass index (BMI) > 30 kg/m2 were admitted to the study. Twenty-seven women received estradiol hemihydrate two mg and 25 did not receive any menopausal therapy. At baseline and after three and six months of treatment, IMA and sCD40 ligand levels were measured. RESULTS: There were no significant differences among the groups for any variables at baseline. No difference in change in the serum sCD40L levels was found in obese surgical menopausal women after three and six months of HT. Serum IMA levels were statistically lowered in obese women with HT after six months of treatment. CONCLUSION: HT may have a beneficial reduction in IMA levels in obese surgical menopausal women.

Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection.

Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥ 20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan-Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.

Natural history and treatment of chronic delta hepatitis.

Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.

The diagnostic value of beta-human chorionic gonadotropin, progesterone, CA125 in the prediction of abortions.

This study was conducted to investigate the effectiveness of serum levels of free beta-hCG, progesterone, CA125 and their combined use in the prediction of first trimester abortions. A total of 140 singleton pregnant women between 5 and 13 weeks' gestational age were included as Group I (n = 21) who resulted in abortion including missed abortion, incomplete abortion, complete abortion and inevitable abortion; Group II (n = 129) included normal pregnancies. When using the free beta-hCG level of <20 ng/ml as a cut off point, the sensitivity, specificity, PPV and NPV were 91%, 82%, 46% and 98%, when using a progesterone of <15 ng/ml as a cut off point, they were 91%, 89%, 59%, 98%. The single measurement of free beta-hCG or progesterone levels can be useful in the prediction of first trimester spontaneous abortions, but using progesterone may be recommended since it has high availability and low cost.

Reduced Activity of von Willebrand Factor after Flow-Diverting Stent Implantation for Intracranial Aneurysms: A Link to Acquired von Willebrand Disease?

BACKGROUND AND PURPOSE: Vascular devices generating high shear stress can cause type 2A acquired von Willebrand disease, which is characterized by low von Willebrand factor activity accompanied by hemorrhagic complications. The braided mesh structure of flow-diverting stents with a relatively small strut size can create abnormally high shear stress while arterial blood flows through the stent struts into the aneurysm, and flow-diverting stent may be associated with reduced von Willebrand factor activity. MATERIALS AND METHODS: Aneurysmal morphologic parameters and patient data were examined retrospectively among patients who had an unruptured intracranial aneurysm treated with a flow-diverting stent. The RISTOtest (test for whole blood ristocetin-induced platelet aggregation) for von Willebrand factor activity, as well as tests for aspirin and clopidogrel/prasugrel effectiveness, were performed immediately before the endovascular procedure and 24 hours later by multiple electrode aggregometry. RESULTS: A total of 39 patients with 56 aneurysms were recruited, and statistical analyses were performed in 32 patents with 49 aneurysms. Compared with the baseline values, von Willebrand factor activity was reduced in 16 patients but increased in 23 patients. Aneurysmal variables (eg, neck area, volume, volume-to-neck area ratio, size ratio, and morphologic index) clearly distinguished patients with reduced von Willebrand factor activity from those with nonreduced von Willebrand factor activity. The receiver operating characteristic curve showed that the morphologic index and volume had the highest discriminative power, with an area under the curve of 0.99. CONCLUSIONS: In high-volume/large-neck aneurysms, flow-diverting stent implantation can cause reduced von Willebrand factor activity, which may be linked causally to acquired von Willebrand disease.

A short course of add-on adefovir dipivoxil treatment in lamivudine-resistant chronic hepatitis B patients.

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/40, mean age: 42.9+/-13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10(7) copies/mL) was a significant predictor of response to ADV treatment (P<0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

Large retroperitoneal schwannoma mimicking ovarian carcinoma: case report and literature review.

UNLABELLED: In this article we present a case of retroperitoneal schwannoma localized in the pelvic cavity with complete cystic degeneration, mimicking ovarian carcinoma. CASE: A 25-year-old nulligravid woman was admitted to our gynecology out-patient clinic with the complaint of abdominal distension, right flank pain and pollakiuria. Sonographic study showed a cytic mass containing necrotic areas and filling the whole pelvic cavity. Computed tomography and colonography suggested the possible diagnosis of a right ovarian malign tumor. Laparotomy revealed a retroperitoneal cystic lesion. Microscopic examination of the pelvic mass confirmed the diagnosis of cystic degenerative schwannoma. After six months of initial surgery she is still alive without any evidence of disease. CONCLUSION: In the present case, it is emphasized that it is easy to make an error and misdiagnose a pelvic mass as an ovarian tumor when it is in fact a tumor from another origin. Additonally, clinicians should keep in mind that retroperitoneal schwannoma may mimic cystic ovarian carcinoma even in young women.

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon.

Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment-naïve, 14 had previously used IFN), efficacy of 1-year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment-naïve patients. In both treatment-naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN-LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN +/- LAM than with LAM alone (P < 0.05). In treatment-naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study.

BACKGROUND: Insulin resistance (IR) is commonly associated with non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) may also play a role in the pathogenesis of NASH. A pivotal role in NASH pathogenesis depends on the hypothesis of increased oxidative stress. The aim of our study was to evaluate the effects of supplemental oral vitamin E, a potent antioxidant, on liver functions, PPAR-alpha expression and IR in patients with NASH. METHODS: Nine patients with biopsy-proven NASH were given oral vitamin E 800 mg daily for 24 weeks. Liver functions, lipid parameters, IR index with homeostatic metabolic assessment and liver histology and PPAR-alpha staining index in biopsy specimens were detected before and after the treatment. RESULTS: Seven patients (78%) had IR initially. After 6 months of therapy in nine patients, fasting insulin improved (P = 0.01), but serum cholesterol, triglyceride, fasting blood glucose levels and body mass index remained unchanged. Aspartate aminotransferase and alanine aminotransferase levels decreased (P = 0.01 and P = 0.01, respectively). IR index with homeostatic metabolic assessment resistance improved (P = 0.01), but PPAR-alpha staining index did not change (P = 0.37). Although the histological grade of steatosis decreased (P = 0.01), necroinflammation and fibrosis remained unchanged. In seven patients with IR, however, necroinflammation and PPAR-alpha staining index were improved (P = 0.04 and P = 0.02). CONCLUSION: Vitamin E treatment, in addition to its previously shown beneficial effect by suppressing oxidative stress, may also achieve improvement by reducing IR and PPAR-alpha expression in NASH.

Pulmonary alterations in patients with chronic HCV infection.

BACKGROUND: Chronic hepatitis C virus infection has been reported in association with several extrahepatic manifestations. Included in this list is interstitial lung involvement. AIMS: The aim of the present study was to evaluate pulmonary alterations in patients with chronic hepatitis C virus infection. PATIENTS: Twenty-one patients with chronic hepatitis C virus infection were enrolled into a prospective study. One patient has been excluded because of underlying tuberculosis. METHODS: All patients underwent pulmonary function tests, diffusion capacity for carbon monoxide and high-resolution computed tomography of the chest. RESULTS: Forced vital capacity, forced expiratory volume in first second/forced vital capacity and forced expiratory volume in first second values were reduced to less than 80% of predicted values in 3, 11 and 5 patients, respectively. Diffusion capacity for carbon monoxide was low in 12 patients (60%), 8 of whom had simultaneous decrease in diffusion capacity for carbon monoxide/VA values. Thorax high-resolution computed tomography revealed abnormal findings in eight patients (40%). Fifteen patients with chronic hepatitis C virus infection (75%) had at least one pulmonary alteration as evidenced by abnormal pulmonary function tests, diffusion capacity for carbon monoxide and/or high-resolution computed tomography results. CONCLUSION: In spite of a limited study population, these findings may implicate that pulmonary manifestations of chronic hepatitis C virus infection are frequently underdiagnosed.

Endovascular management of congenital arteriovenous fistulae in the neck.

PURPOSE: The purpose of this study was to evaluate congenital arteriovenous fistulae in the neck, including vertebrovertebral and carotico-jugular arteriovenous fistula, with their endovascular management. MATERIALS AND METHODS: Six patients with congenital arteriovenous fistulae in the neck who underwent endovascular treatment between March 2001 and December 2013 at the Department of Radiology, Ege University School of Medicine were enrolled into this retrospective study. There were four men and two women, with a mean age of 8.6 (range 4-17)years. Patients' demographics and symptoms were noted. Diagnostic computed tomography and/or magnetic resonance angiography were available in all patients. Parent artery and vein of the arteriovenous fistula, location of the fistula, the other features of fistula, endovascular occlusion site, number and type of endovascular materials, and length of follow-up were reviewed. RESULTS: Four patients had vertebrovertebral fistula, while two patients had carotido-jugular fistula (fistula between maxillary artery and external jugular vein). Four patients underwent detachable balloon occlusion together with coil embolization, while two patients underwent detachable balloon occlusion only. The parent artery was occluded in five patients without clinical consequences, and the remaining fistula was occluded with preservation of the parent artery. The patients did not have any complication in the follow-up period (mean follow-up, 9months). CONCLUSION: Congenital arteriovenous fistulae in the neck are extremely rare. Endovascular fistula occlusion with parent vessel sacrifice appears to be a safe and minimally invasive treatment option with good results during the follow-up period.

The short- and long-term effectiveness of transcatheter arterial embolization in patients with intractable hematuria.

PURPOSE: Selective transarterial embolization (TAE) of the internal iliac artery is a well-known alternative technique to control intractable bladder hemorrhage (IBH). We explored the short- and long-term effectiveness of, and clinical outcomes after, TAE in patients with IBH. MATERIALS AND METHODS: In this retrospective study, we reviewed the hospital records of 18 IBH patients non-responsive to conservative medications who underwent TAE between January 2003 and May 2014. The early- and long-term effectiveness of TAE was investigated in the context of hematuria control, complications, mortality, requirement for blood transfusions, and hematocrit level. RESULTS: Sixteen of the 18 patients underwent endovascular treatment; the technical success rate was 88%. TAE allowed complete remission in 16 patients (100% clinical success). On follow-up, mean hematocrit (P=0.003) and hemoglobin (P=0.005) levels significantly improved. Thirteen of the 16 patients (81%) required no further emergency admission after TAE during a mean follow-up period of 18.1months (range, 3-105months). CONCLUSION: TAE is a feasible, effective, and safe technique in both the short- and long-term for the treatment of IBH.

The relationship between mutant p53 gene, DNA contents and conventional clinicopathological prognostic variables in cases with endometrial carcinoma.

PURPOSE OF INVESTIGATION: To determine whether p53 expression and DNA ploidy are related to traditional prognostic indicators in patients with endometrial cancer. METHODS: Tumor material (n=136) was analyzed regarding flow cytometric DNA ploidy and immunohistochemical p53 expression. Pearson's correlation, Fisher's exact test, Cox's regression analysis and the Kaplan-Meier survival test were used, as appropriate. RESULTS: P53 overexpression and DNA ploidy were higher in patients with nonendometrioid histology, FIGO advanced stage, poor grade, positive peritoneal cytology, lymphovascular space invasion (LVSI) and lymph node involvement (LNI). Histologic subtype, stage, grade, LVSI, LNI, tumor recurrence and overall survival rate correlated with p53 and DNA ploidy. No association of depth of myometrial invasion and age with p53 and DNA ploidy was observed. P53 was related to DNA ploidy. Of the factors analyzed, histologic subtype and myometrial invasion were found to be most important independent determinants of recurrence. Utilizing survival as the endpoint for multivariate analysis, when considering p53 and DNA ploidy together, histologic subtype, stage, peritoneal cytology, LNI and DNA ploidy were independent prognostic indicators. CONCLUSION: p53 expression and DNA ploidy were related to histologic subtype, FIGO stage, grade, LVSI, LNI, peritoneal cytology, tumor recurrence and overall 5-year survival. As compared to p53, DNA ploidy was the stronger independent predictor factor for survival. Neither p53 nor DNA ploidy were significant independent factors for tumor recurrence when submitted to multivariate analysis in this study. However, since p53 or DNA ploidy were found to be significant factors in univariate analysis and were correlated with tumor recurrence, they could be useful factors in making prognoses.

Nucleotide divergences in the core promoter and precore region of genotype D hepatitis B virus in patients with persistently elevated or normal ALT levels.

BACKGROUND: Mutation in the hepatitis B virus precore codon 28, creating a translational stop codon and double 1762-1764 T/A mutations in the core promoter region, controlling the transcription of the precore RNA and the core RNA have been suggested to correlate with the HBeAg status of patients with HBV infection. OBJECTIVES: The aim of the study was to further investigate the association of nucleotide divergences in both core promoter and precore regions with liver cell injury (reflected by ALT levels) in patients with chronic HBV infection. STUDY DESIGN: The sequences of the core promoter and the precore region of HBV isolated from 67 patients, all having genotype D and subtype ayw were analyzed. The patients were divided into two groups and four subgroups according to their HBeAg and Anti-HBe status, and ALT profile. RESULTS: It was found that the nucleotide divergences in the core promoter but not in the precore region were higher in patients having persistently elevated serum ALT than in serum ALT normal patients in both HBeAg positive and Anti-HBe positive groups (P<0.05). The number of T/A and A1896 stop codon mutations did not yield a statistically significant difference between ALT normal and elevated groups. It was also found that 1762-1764 T/A and precore A 1896 mutation existed in five and six out of 29 HBeAg positive patients, respectively. In 38 anti-HBe positive patients, 1762-1764 T/A and precore A1896 mutation were detected in three and 16 patients respectively, and coexisted in 10 patients. CONCLUSIONS: Precore A 1896 stop codon mutation seems to play an essential role in the loss of HBeAg in Turkish patients. Serum viremia levels of HBV in patients having precore stop codon and/or T/A mutation were not significantly different from the other patients carrying wild type strains. Nucleotide variability in the core promoter region may be one of the factors linked to hepatitis B disease activity.