Prevalence and Clinical Features of Celiac Disease in Healthy School-Aged Children.

BACKGROUND/AIMS: The aim of this study was to determine the prevalence of celiac disease (CD) in healthy school-aged children in the northern region of Cyprus and to investigate the existence of potential markers that may accompany CD. This is the first study to measure the prevalence of CD in the northern region of Cyprus. METHODS: This study included 3792 school-aged children who were between the ages of 6 and 10 years between January 2015 and October 2016. CD was screened using total serum IgA, IgA anti-tissue transglutaminase (tTG), and IgA antiendomysial (EMA) antibodies. Subjects with selective IgA deficiency were further tested for IgG-tTG. Small intestinal biopsies were performed on all subjects with tTG antibody positivity. Risk factors and symptoms related to CD were evaluated using questionnaires in both the CD and control groups. RESULTS: Of the 3792 subjects, 39 were antibody positive (IgA-tTG was positive only in 14 subjects, IgA-tTG plus IgA-EMA in 21 subjects, and IgG-tTG in 4 subjects). IgA deficiency was detected in 11 subjects (0.29%). IgG-tTG was positive in 4 subjects with IgA deficiency (36.3%). Intestinal biopsies were performed on 28 of the 39 seropositive subjects. The biopsy findings of 15 children were consistent with CD (IgA-tTG positive in 3, IgA-tTG and IgA-EMA positive in 10, and IgG-tTG positive in 2). Thus, biopsies confirmed CD in 1:256 children (0.39%). CONCLUSIONS: Our study, which is the first study of school-aged children from the northern region of Cyprus, revealed that CD is a prevalent disease in this region.

Prevelance of hepatitis D co-enfection in children with hepatitis B infection: cross-sectional analyses from Western Turkey.

BACKGROUND/AIMS: Effective hepatitis B virus control has warranted a decline in hepatitis B virus prevalence over the world with a relevant reduction in hepatitis B virus-associated delta hepatitis. However, despite the dramatic decline in hepatitis D virus infection rate, no further decrease was recorded after 2000. This cross-sectional study aims to investigate: I- The prevalence of hepatitis D virus co-infection in children with hepatitis B virus infection in Western Turkey; II- The influence of neonatal hepatitis B virus vaccination on hepatitis D virus co-infection rate; and III- The impact of co-infection on prognosis of liver disease. MATERIALS AND METHODS: Serological markers of hepatitis B virus and hepatitis D virus infections were determined by ELISA in patients with chronic hepatitis during immune tolerance, immunoactive, HBeAg-negative chronic, and inactive carrier state. Delta co-infection rate was evaluated in two groups, children born before and after the national neonatal mass vaccination has started (before and after 2000). Viral load, serum alanine aminotransferase, and histological grade were evaluated in co-infected cases. RESULTS: Overall hepatitis delta virus infection rate was 1,76% (3/170); two patients with eAg-negative chronic hepatitis B and one patient in the immunoactive phase were infected with hepatitis D virus. Mean fibrosis score of hepatitis D virus -infected cases and hepatitis B virus -infected counterparts were 4±1,7 and 1,3±1, respectively (p: 0,006). Hepatitis D virus infection was detected in 2 out of 158 children born before and in 1 of 12 born after the neonatal vaccination program. Hepatitis B e-antibody was detected in two patients with delta co-infection (11 and 6 years old), and all mothers of delta hepatitis cases were chronically hepatitis B virus-infected. CONCLUSIONS: Delta hepatitis is rare among hepatitis B virus-infected children in the Western region of Turkey. Despite the success of the national vaccination program, delta hepatitis is not a vanishing disease and it has a grave prognosis due to development of early cirrhosis.

The diagnostic value of multimodal evoked potentials in the determination of subclinical neurological involvement of Wilson's disease.

AIMS: Wilson's disease (WD) is a progressive degeneration of hepatolenticular tissue caused by excessive tissue-damaging copper accumulation and in which liver involvement most frequently presents in childhood. Neurological signs also accompany liver disease with time. However, subclinical neurological involvement may occur earlier and diagnostic methods that reveal this subclinical involvement are not well established. The aim of the current study is to assess the subclinical neurological involvement by using multimodality evoked potential (EP) measurements and to explore the relationship between neurological disease and the severity of liver damage. METHODS: The patient group included 28 children (mean age 11.8 ± 2.9 years, range 5.5-17) diagnosed with WD and a control group included 24 age-matched healthy children. Multimodality EP tests (Nihon Kohden Neuropack 8 4200K) of both groups were performed at the Department of Neurology Electrophysiology Laboratory of Ege University. RESULTS: At least one abnormal EP value was observed in 53.5% of the children in the patient group. At least on one side, there were abnormal values for visual evoked potential (VEP) P100, brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP), where the ratios were 25, 28.5, and 11%, respectively. Absolute latency values of patients with right-side VEP P100 and left-side BAEP I, and the interpeak latency values of right-side BAEP I-III were significantly high. The difference in right-side BAEP I-III interpeak latency between cirrhotic and noncirrhotic groups was found to be statistically significant (P<0.05). CONCLUSION: The EP examinations can be an indicator of subclinical brain damage in non-neurological WD; however, cirrhosis because of WD does not cause an increase in the EP values. Detection of changes in the EP values periodically, especially at the time of diagnosis and during the treatment follow-up, may be valuable for revealing subclinical impairment.

Gastroesophageal reflux in children with functional constipation.

BACKGROUND/AIMS: Functional constipation and gastroesophageal reflux disease are two major and commonly encountered components of childhood functional gastrointestinal disorders. Epidemiological studies in the adult population support that there is a significant overlap between the different functional disorders of the digestive tract. Therefore, we aimed to investigate the frequency of gastroesophageal reflux disease in children with functional constipation and to compare clinical findings and 24-h esophageal pH monitoring with a group of patients with suspected gastroesophageal reflux disease. MATERIALS AND METHODS: Children between 4 and 16 years old with functional constipation (based on Rome III criteria, Group 1; n=38) were prospectively evaluated. A control group was composed of patients with symptoms suggesting gastroesophageal reflux disease (Group 2; n= 40). All patients included in the study were asked about reflux-related symptoms, and then all cases underwent 24-h esophageal pH monitoring analysis. RESULTS: Delayed gastric emptying symptoms such as belching and hiccups were more common in patients in Group 1 (p=0.002, p=0.021, respectively), whereas chronic cough was more common in patients in Group 2 (p=0.012). According to the 24-h esophageal pH monitoring, pathologic acid reflux in the lower and/or laryngopharyngeal portion of the esophagus was determined in 39.5% of the patients in Group 1 and in 42.5% of the patients in Group 2 (p=0.96). No significant difference was found in terms of age, gender and duration of constipation in patients with and without acid reflux in Group 1 patients. Pyrosis (66.6 vs. 0%, p=0.00001)was more common in Group 1 patients with acid reflux, but hiccups (20 vs. 69.5%, p=0.007) and belching (33.3 vs. 60.8%, p=0.184) were more common in patients in Group 1 without acid reflux. CONCLUSIONS: Gastroesophageal reflux disease should be considered in the treatment and monitoring of patients with functional constipation. Further studies are needed using 24-h pH multichannel impedance.

Peptic ulcer disease in children: an uncommon disorder with subtle symptomatology.

BACKGROUND/AIMS: Data concerning peptic and infectious ulcers in children are limited. The aim of the study was to investigate the prevalence, presenting symptoms and significance of symptomatology in ulcer diagnosis in the pediatric age group. MATERIALS AND METHODS: Between January 2000 and 2009, upper gastrointestinal endoscopy charts were examined retrospectively. All children in whom a diagnosis of ulcer was established were included in the study. Demographic, clinical, endoscopic, and histopathologic data were obtained from the patients' records. Peptic ulcer disease prevalence, presenting symptoms and symptomatology were evaluated. RESULTS: Ulcer disease was observed in 31 (3.4%) of 902 patients. The mean age was 10.85 ± 4.25 (range: 2-17 years), and the male to female ratio was 2:1. The most common symptom was chronic abdominal pain (68%), hematemesis and melena (55%) and vomiting (39%). Helicobacter pylori was identified in 19 patients (61%) with ulcer. In the Helicobacter pylori-positive group, upper intestinal bleeding and pain were the major symptoms. Symptom frequency was not different between Helicobacter pylori-positive and -negative patients (p>0.05). CONCLUSIONS: Ulcer disease is an uncommon disorder in children with nonspecific clinical symptoms. Unlike the adult population, symptoms fail to diagnose peptic ulcer disease before gastrointestinal bleeding occurs.

Dietary vitamin A intake and serum retinol concentrations of preschool children from different socio-economical levels in Izmir, Turkey.

AIM: Vitamin A deficiency (VAD), especially in its subclinical form, is a world health problem in young children. The aim of this study was to determine the prevalence of VAD among preschool children in various socio-economic groups in Izmir, Turkey. METHODS: One hundred and one children aged 24-59 months were selected for the study with cluster sampling method. A questionnaire was completed by the parents, and the dietary pattern was assessed by using a 3-day dietary record method. RESULTS: Mean serum retinol concentration of the children was 28.3 ± 10.2 µg/dL. Serum vitamin A concentration of two children (2%) was below 10 µg/dL (VAD), whereas 18 (18%) children had vitamin A concentrations between 10 and 20 µg/dL (subclinical deficiency). We did not find any relationship between mean serum retinol concentrations and the independent variables such as socio-economical levels, age groups, birth weight and gestational age. However, there was a statistically significant positive correlation between serum retinol concentrations and weight-for-age and weight-for-height Z scores of the children (p < 0.05). CONCLUSION: Because one-fifth of the children under 5 years have VAD in Izmir, Turkey, nutrition education must be given to the families during well-child care visits, and routine vitamin supplementation should be considered especially in children with malnutrition.

Steroid response in moderate to severe pediatric ulcerative colitis: a single center's experience.

BACKGROUND: we aimed to analyze clinical and inflammatory markers of steroid non-response in patients with moderate/severe ulcerative colitis (UC) at the time of diagnosis. METHODS: this study included patients who were graded as having moderate/severe UC and received corticosteroids as first-line therapy. Demographic, clinical and laboratory findings and pediatric ulcerative colitis activity scores (PUCAS) were recorded. Response to corticosteroids was assessed 30 days after the induction and long-term therapy. RESULTS: twenty-eight children were diagnosed as having moderate/severe UC. Their mean age ± SD was 1 2.2 ± 4 years, and 17% were under 5 years of age. PUCAS at their initial admission was 56.9 ± 11.8. UC was observed at the left colon in 9 patients (32.1%), and pancolitis in 19 (67.9%). At the end of the 30th day, UC was completely remitted in 15 patients (53.5%), partially remitted in 2 (7.1%), and no response in 11 (39.2%). Short-term follow-up showed partial remission in 2 patients, and overall remission with steroid in 17 (60.7%). Non-responders were given second-line treatment; steroid dependency was documented in 2 patients (7.1%) and another 2 (7.1%) patients underwent colectomy. Predictors for steroid non-response were analyzed and only PUCAS at the initial admission was found to be associated with non-response to steroids (51.4 ± 11.4 vs. 65.4 ± 6.8, P<0.05). CONCLUSIONS: approximately half of the pediatric patients had complete response to steroid therapy in a long period. PUCAS could be used as a potential marker of "failed response" to steroid, but should be supported with a number of prospective randomized controlled studies.

Determination of intracellular Th1/Th2 type cytokines in lymphocytes of chronic hepatitis B patients treated with interferon-alpha.

BACKGROUND/AIMS: Host-related immune factors in childhood chronic hepatitis B and change in the initial profile with interferon (IFN)-α treatment need to be clarified. METHODS: Sixteen patients were included in the study, and 10 million units of IFN-α treatment 3 times per week for 6 months was initiated. Pre- and post-treatment percentages of interleukin (IL)-2 and IFN-γ in CD4+ T cells were assessed to determine intracellular T helper cell 1 (Th1) type cytokine expression. Similarly, percentages of intracellular IL-2 and IFN-γ were detected to verify cytotoxic T cell 1 (Tc1) type cytokine expression in CD8+ T cells. Percentages of Th2 and Tc2 type cytokine expression (IL-4 and IL-13) were determined in CD4+ and CD8+ T cells, respectively. RESULTS: Six (50%) of these were evaluated as having no response and the other half with partial/complete response. All patients had higher percentages of Th2 cells with respect to healthy controls pre-treatment. Tc percentages, both Tc1 and Tc2, were significantly different between these groups, being higher in the patient group. When values of the nonresponder group were compared with healthy controls, IL-4 expression was higher and the percentages of Th1 type cells were significantly low. IL13 expression in Th and Tc cells decreased after 6 months of treatment in the unresponsive group. The decrease we observed in Th1 percentages with treatment, in the responsive group, may be due to Th1 deposition shifting from the periphery to liver tissue, as reported before. Intracellular cytokine profiles of treatment responders and normal controls were not different. RESULTS: This is the first study in children comparing baseline and post-treatment intracellular cytokine profiles with values in healthy controls.

Giant cell hepatitis and autoimmune hemolytic anemia after chickenpox.

Autoimmune hemolytic anemia with giant cell hepatitis is a distinct entity in children. It is usually fatal with progressive liver disease. Immunosuppressive treatment with conventional drugs offers some response; however, it is usually only temporary. Alternative therapeutic options with monoclonals have been reported with promising remission of the disease. We report a case with autoimmune hemolytic anemia+giant cell hepatitis after varicella infection. She was resistant to standard immunosuppressive combinations, and rescue therapy with rituximab was used. Remission was not achieved with the drug and the child died with septic complication.

A rare cause of refractory ascites in a child: familial Mediterranean fever.

Familial Mediterranean fever (FMF) is hereditary episodic febrile syndrome characterized by acute attacks of fever and serosal inflammation, generally lasting 1-3 days and resolves spontaneously. Apart from abdominal pain, patients may present with variety of abdominal manifestations such as acute peritonitis, mechanical intestinal obstruction, diarrhea, bowel infarction, amyloidosis and small amounts of peritoneal fluid during the acute attacks. A 6-year-old boy was admitted with massive ascites. After extensive laboratory investigations, no causative agent could be identified. On subsequent days, he developed fever and skin eruptions. Acute-phase reactants were increased. A second tomography revealed cystic fluid collection near the anterior side of spleen that invades the stomach. An exploratory was performed and histopathological examination of the all resected specimens revealed mix inflammatory cell infiltrate associated with severe myofibroblast proliferation suggesting chronic inflammatory process on the mesenteric region. A diagnosis of FMF was suspected based on the clinical, laboratory and histopathological findings, and a trial of colchicine therapy initiated. Ascites and other serosal inflammations improved within 1 week without any recurrence during the next 12-month period on colchicine treatment. Atypical presentations of FMF have been increasingly reported. Pediatricians should keep FMF in mind in the differential diagnosis of massive ascites especially in regions where hereditary inflammatory disease are common.

Infectious complications in pediatric liver transplantation candidates.

We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.

Chronic constipation in Turkish children: clinical findings and applicability of classification criteria.

We aimed to evaluate general features of children with chronic constipation and classified them according to the Iowa criteria and Rome II criteria in order to analyze applicability of these criteria in our population. The medical records of 485 children who were referred for chronic constipation over a six-year period were evaluated retrospectively. We found that 7.7% of the cases had an organic pathology, and short segment Hirschsprung disease was the leading cause. Other children (92.3%) were classified as functional constipation, with a mean age of 6.4 +/- 4 years and with slight male dominance. Encopresis was found in 117 children (51.7%) aged over four years, and was associated with older age, male predominance and long duration of symptoms. Both of the classification systems showed a similar prevalence of constipation, but 9.9% of the children with pediatric constipation were not recognized by Rome II criteria. Additionally, 1.8% of the children were not recognized by either Iowa or Rome criteria. Functional constipation is common in primary care, and most of the children were school-aged. Constipation associated with encopresis and nutritional problems such as obesity is less common in developing countries. Rome II criteria are too restrictive and do not recognize approximately 12% of the children. A new classification system must be simple, easy to understand especially by the primary care physician, and must include the common features of constipation recognized by the parents.

Long-term effect of gluten-free diet on growth velocity in Turkish children with celiac disease.

We sought to analyze the long-term growth in children with celiac disease (CD) as well as the association of height and weight SD score at the end of 4 years with the demographic and clinical presentation at initial admission. Thirty-four children with CD were enrolled in the study and followed for at least 4 years. Patients were divided into three groups (Group 1: patients 10 years, at the time of diagnosis). Patients' charts were reviewed for demographic and clinical features at initial admission. Anthropometric measurements at initial admission, at 6th months, and 1st, 2nd, 3rd, and 4th years were recorded. Gluten-free diet led to rapid increase in weight SD and height SD score in patients

A rare complication of central catheter in an infant with intestinal failure.

OBJECTIVE: To report the successful percutaneous transcatheter removal of a snapped intracardiac fragment of the central vein catheter in an infant. CLINICAL PRESENTATION AND INTERVENTION: A 3-month-old infant with short bowel syndrome who required long-term parenteral nutrition via portacath central catheter was hospitalized. Two months after the insertion of the second catheter, the distal tip of the catheter snapped and became tangled in the heart. The catheter fragment was removed by a percutaneous femoral vein approach using a 10-mm diameter snare-loop catheter (Amplatz). The procedure was performed under fluoroscopy; the fragment was removed after being released into the right ventricle by pulling the proximal tip with a pigtail catheter. No complications were observed and the patient was transported back to the intensive unit in stable condition. CONCLUSION: Central catheter-related complications may cause difficulties in patients with short bowel syndrome prior to intestinal transplantation. The percutaneous retrieval of the fragmented catheter using a snare-loop catheter is a safe and reliable technique and may be used instead of surgery especially in small infants.

Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation.

OBJECTIVES: The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era. METHODS: Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2-22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar-arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation. RESULTS: HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75-10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month. CONCLUSIONS: HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients.

Nutritional status of infants with neonatal cholestasis.

PURPOSE: We constructed a study to determine the association of anthropometric measurements, biochemical parameters and bone mineral content with nutritional status in infants with neonatal cholestasis. METHODS: The study included 38 children with neonatal cholestasis. Nutritional status was assessed by Waterlow criteria, and anthropometric measurements, biochemical parameters and bone mineral content were correlated with the nutritional status at initial admission and at the end of 2 months after nutritional support. RESULTS: We found that the prevalence of acute and chronic malnutrition was 34.2% and 39.4% in infants with neonatal cholestasis, respectively. No significant difference was found in triceps skinfold thickness (TST), scapular skinfold thickness (SST) and suprailiac skinfold thickness (SuST), arm fat area (AFA) and arm area (AA) among the groups. Mid-arm circumference (MAC), arm muscle circumference (AMC) and arm muscle area (AMA) were significantly lower in patients with chronic malnutrition than both acute malnutrition and patients without malnutrition. MAC was the most reliable marker for the assessment of malnutrition and had the highest positive predictive value (PPV) (80.6%), sensitivity (89.2%) and negative predictive value (NPV) (57.1%). Prealbumin levels were significantly lower in patients with chronic malnutrition than the patients without malnutrition. Increment in MAC and AMC were significantly high in the three groups after 2 months. CONCLUSION: MAC is a good indicator of malnutrition in neonatal cholestasis and may also be used for the monitoring of nutritional support; prealbumin may be used for assessment of the severity of malnutrition.

The influence of marginal zinc deficient diet on post-vaccination immune response against hepatitis B in rats.

AIM: To evaluate in vitro T lymphocyte proliferation and specific antibody response to hepatitis B vaccination in two groups of rats fed with normal and marginal zinc content. METHODS: Twenty-two Wistar-Albino rats were randomly assigned into two groups and were fed with constant diet. Zinc was suplemented 10mg/kg dry weight in group I (marginal zinc content) (n=14) and 30mg/kg dry weight in group II (n=8). Hepatitis B vaccine (Engerix B, 4mug) was administered intramuscularly after 8 weeks on feeding and a booster dose was applied 4 weeks after the first injection. Rats were killed 3 weeks after the second injection. Peripheral blood mononuclear cells were stimulated in vitro by PHA (2.5mug/ml) and hepatitis B surface antigen (2.5, 5, 10mug/ml). Proliferation was evaluated by ELISA (celltiter-96 aqueous one solution cell proliferation assay). Serum zinc, anti-HBs titer and zinc per dry liver weight were also measured. Two groups were compared with respect to antigen specific antibody and lymphocyte proliferation responses. Proliferation response to HbsAg were expressed as net percent increase (pci) in lymphocyte proliferation from the baseline activity. RESULTS: Rats' mean body weight and weight gain per month were similar. Median serum zinc was 39 (23-75) and 76(64-115)mug/dl of groups I and II rats, respectively (p<0.05), while there was no difference in liver zinc content between the two groups (37mug/g dry weight versus 32mug/g dry weight). Median anti-HBs levels of groups I and II were 741 (0-10,000)IU/l, 5791 (558-10,000)IU/l, respectively (p<0.05). In lymphocyte proliferation assays, mean net pci with HbsAg of 5 and 10mug/ml were 9.4% and 11.3% in group I rats; while they were 25.3% and 26.1% in group II rats (p<0.01 and p<0.01, respectively). CONCLUSION: In vitro cell-mediated immune response and in vivo specific antibody response to hepatitis B vaccine was decreased in rats fed a diet with marginal zinc content. These observations have shown that marginal Zn deficiency might influence the efficacy of hepatitis B vaccination in humans.

Comparison of two different regimens of combined interferon-alpha2a and lamivudine therapy in children with chronic hepatitis B infection.

AIM: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN-alpha2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. METHODS: A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6 months. In group I (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/- 3.8 years) 3TC was started 2 months prior to IFN-alpha2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months in nonresponders. RESULTS: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II, respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and II, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05). Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders. CONCLUSION: Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier antiHBe seroconversion and viral clearance than consecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can be administered for 24 months without any side effect and breakthrough rate is comparable with previous studies.