Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations.

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries.

BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries. METHODS: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification. RESULTS: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia. CONCLUSION: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality.

Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions.

BACKGROUND & AIMS: To analyse elastographic characteristics of focal liver lesions (FLL)s and diagnostic performance of real-time two-dimensional shear-wave elastography (RT-2D-SWE) in order to differentiate benign and malignant FLLs. METHODS: Consecutive patients diagnosed with FLL by abdominal ultrasound (US) underwent RT-2D-SWE of FLL and non-infiltrated liver by intercostal approach over the right liver lobe. The nature of FLL was determined by diagnostic work-up, including at least one contrast-enhanced imaging modality (MDCT/MRI), check-up of target organs when metastatic disease was suspected and FLL biopsy in inconclusive cases. RESULTS: We analysed 196 patients (median age 60 [range 50-68], 50.5% males) with 259 FLLs (57 hepatocellular carcinomas, 17 cholangiocarcinomas, 94 metastases, 71 haemangiomas, 20 focal nodular hyperplasia) of which 70 (27%) were in cirrhotic liver. Malignant lesions were stiffer (P < .001) with higher variability in intralesional stiffness (P = .001). The best performing cut-off of lesion stiffness was 22.3 kPa (sensitivity 83%; specificity 86%; positive predictive value [PPV] 91.5%; negative predictive value [NPV] 73%) for malignancy. Lesion stiffness <14 kPa had NPV of 96%, while values >32.5 kPa had PPV of 96% for malignancy. Lesion stiffness, lesion/liver stiffness ratio and lesion stiffness variability significantly predicted malignancy in stepwise logistic regression (P < .05), and were used to construct a new Liver Elastography Malignancy Prediction (LEMP) score with accuracy of 96.1% in validation cohort (online calculator available at http://bit.do/lemps). CONCLUSION: The comprehensive approach demonstrated in this study enables correct differentiation of benign and malignant FLL in 96% of patients by using RT-2D-SWE.

Online combination algorithm for non-invasive assessment of chronic hepatitis B related liver fibrosis and cirrhosis in resource-limited settings.

OBJECTIVE: The use of commercially available noninvasive markers for chronic hepatitis B (CHB) related fibrosis is not widely available in developing countries so clinicians in those countries frequently use free alternatives. We aimed to create an optimized algorithm for selection of patients with the highest probability for presence/absence of significant liver fibrosis and cirrhosis based on the use of multiple free scores. METHODS: We evaluated six free noninvasive markers for CHB related fibrosis against liver biopsy and selected the best thresholds for prediction/exclusion of significant fibrosis and cirrhosis in CHB patients. Algorithm based on four scores and their corresponding thresholds was created. RESULTS: The calculator based on developed algorithm can be found at http://www.chb-lfc.com. We evaluated 211 patients in main group and 65 patients in external validation group. We selected four scores for creation of combination algorithm. The algorithm was able to classify 123/211 (58.3%) patients with a 93.5% accuracy of correct classification for prediction of presence/absence of significant fibrosis in main group. In validation group, the algorithm was able to classify 48/65 (73.8%) of patients with 93.8% (45/48) overall accuracy. When used to predict presence/absence of cirrhosis, the algorithm was able to correctly classify 181/211 (85.8%) and 59/65 (90.8%) of patients in main and validation group, respectively, with an overall accuracy of 97.8% and 98.3%, respectively. CONCLUSION: Developed algorithm based on routine laboratory tests is a usable, applicable and accurate tool for diagnosis of CHB related fibrosis and cirrhosis, suitable for resource-limited settings where more expensive modalities are unavailable.

NOD2/CARD15 mutations in Polish and Bosnian populations with and without Crohn's disease: prevalence and genotype-phenotype analysis.

Data on prevalence and phenotypic consequences of nucleotide-binding oligomerisation domain 2/caspase recruitment domains 15 (NOD2/CARD15) variants in Crohn's disease (CD) population in Poland and Bosnia and Herzegovina (B&H) are nonexistent. We aimed to determine the prevalence of NOD2/CARD15 mutations and their association with disease phenotype in Polish and Bosnian patients with CD and in healthy controls. We prospectively recruited 86 CD patients and 83 controls in Poland and 30 CD patients and 30 controls in B&H, 229 in total. We determined the prevalence of NOD2/CARD15 mutations and their association with the disease phenotype according to Montreal classification. Participants were genotyped for Leu1007fsinsC and Gly908Arg mutations. At least one CD-associated allele was found in 29/86 (33.7%) of Polish CD patients and in 9/83 (10.8%) of healthy controls (p<0.001). In both CD patients and controls in Bosnian sample, at least one NOD2 mutation was found in equal number of patients (3/30; 10%) with all of the NOD2 mutation positive CD patients being homozygous, while controls being heterozygous. In Polish sample, perianal disease was less frequent in CD patients with any NOD2 mutation (1/21; 4.8%) compared to those without (11/41; 26.8%; p=0.046). Higher percentage of patients with NOD2 mutations had history of CD related surgery when compared with those without mutations (66.7% vs. 43.3%; p=0.05). The risk for CD is increased in patients with NOD2 mutations (Poland) and especially in the presence of homozygous NOD2 mutations (Poland and Bosnia). The presence of variant NOD2 alleles is associated with increased need for surgery and reduced occurrence of perianal disease.

Artificial neural network predicts the need for therapeutic ERCP in patients with suspected choledocholithiasis.

BACKGROUND: Selection of patients with the highest probability for therapeutic ERCP remains an important task in a clinical workup of patients with suspected choledocholithiasis (CDL). OBJECTIVE: To determine whether an artificial neural network (ANN) model can improve the accuracy of selecting patients with a high probability of undergoing therapeutic ERCP among those with strong clinical suspicion of CDL and to compare it with our previously reported prediction model. DESIGN: Prospective, observational study. SETTING: Single, tertiary-care endoscopy center. PATIENTS: Between January 2010 and September 2012, we prospectively recruited 291 consecutive patients who underwent ERCP after being referred to our center with firm suspicion for CDL. INTERVENTIONS: Predictive scores for CDL based on a multivariate logistic regression model and ANN model. MAIN OUTCOME MEASUREMENTS: The presence of common bile duct stones confirmed by ERCP. RESULTS: There were 80.4% of patients with positive findings on ERCP. The area under the receiver-operating characteristic curve for our previously established multivariate logistic regression model was 0.787 (95% CI, 0.720-0.854; P < .001), whereas area under the curve for the ANN model was 0.884 (95% CI, 0.831-0.938; P < .001). The ANN model correctly classified 92.3% of patients with positive findings on ERCP and 69.6% patients with negative findings on ERCP. LIMITATIONS: Only those variables believed to be related to the outcome of interest were included. The majority of patients in our sample had positive findings on ERCP. CONCLUSIONS: An ANN model has better discriminant ability and accuracy than a multivariate logistic regression model in selecting patients for therapeutic ERCP.

FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta-analysis.

OBJECTIVES: Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis. METHODS: MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity. RESULTS: We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78-0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48-72%), 80 (72-86%), and 6.2% (3.3-11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85-0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47-75%), 91 (88-93%), and 15.7% (8.6-28.8), respectively. CONCLUSIONS: FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy.

Allele frequency distribution of 1691G >A F5 (which confers Factor V Leiden) across Europe, including Slavic populations.

UNLABELLED: The allele 1691A F5, conferring Factor V Leiden, is a common risk factor in venous thromboembolism. The frequency distribution for this allele in Western Europe has been well documented; but here data from Central, Eastern and South-Eastern Europe has been included. In order to assess the significance of the collated data, a chi-squared test was applied, and Tukey tests and z-tests with Bonferroni correction were compared. RESULTS: A distribution with a North-Southeast band of high frequency of the 1691A F5 allele was discovered with a pocket including some Southern Slavic populations with low frequency. European countries/regions can be arbitrarily delimited into low (group 1, <2.8 %, mean 1.9 % 1691A F5 allele) or high (group 2, ≥2.8 %, mean 4.0 %) frequency groups, with many significant differences between groups, but only one intra-group difference (the Tukey test is suggested to be superior to the z-tests). CONCLUSION: In Europe a North-Southeast band of 1691A F5 high frequency has been found, clarified by inclusion of data from Central, Eastern and South-Eastern Europe, which surrounds a pocket of low frequency in the Balkans which could possibly be explained by Slavic migration. There seem to be no indications of variation in environmental selection due to geographical location.

Predictive score for anastomotic leakage after elective colorectal cancer surgery: a decision making tool for choice of protective measures.

BACKGROUND: Anastomotic leakage is the most severe complication after colorectal surgery and a major cause of postoperative morbidity and mortality. We aimed to identify a predictive score for postoperative leakage after colorectal cancer surgery and to evaluate its usefulness in assessing various protective measures. METHODS: A total of 159 patients were divided into test (79 patients) and validation (40 patients) groups in order to identify the risk factors and construct the predictive score. The remaining 40 patients (intervention group) were prospectively evaluated with the application of protective measures guided by risk stratification according to the predictive score. RESULTS: A total of 23 of 159 (14.5 %) patients had anastomotic leakage, with 7 of 23 (30.4 %) of them needing reoperation. 11 of 159 (6.9 %) patients died, with 10 (6.3 %) deaths directly associated with anastomotic leakage. The rate of leakage in the test and validation groups (nonintervention group) was 22 of 119 (18.5 %), while the rate of leakage in the intervention group was 3 of 40 (7.5 %). The odds ratio for anastomotic leakage in the intervention group was 0.23 compared to the nonintervention group, with a relative risk reduction of 73 % for unfavorable event. The number needed to treat was 8 patients. There were also 10 of 119 (8.4 %) deaths in the nonintervention group compared to 1 of 40 (2.5 %) in the intervention group (Fisher's test; p = 0.18). CONCLUSIONS: Our simple predictive score may be a valuable decision making tool that can help surgeons reliably identify patients at high risk for postoperative anastomotic leakage and apply guided intraoperative protective measures.

Enhanced therapeutic response with addition of loratadine in subserosal eosinophilic gastroenteritis.

A case of a 45-year-old Caucasian male initially reported with symptoms of acute intestinal obstruction was presented. Diagnostic tests revealed presence of eosinophilic ascites with marked peripheral eosinophilia, a significant thickening of stomach and intestinal wall and infiltration of gastric and duodenal mucosa with eosinophiles. Findings were conclusive with subserosal type of eosinophilic gastroenteritis and the patient's treatment started with a combination of parenteral methylprednisolone and oral loratadine. A prompt clinical response was encountered after 5 days of treatment with complete resolution.

Acute pancreatitis after kidney transplantation.

Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient.

Prevalence of 1691G>A FV mutation in Poland compared with that in other Central, Eastern and South-Eastern European countries.

The 1691G>A FV variant has been described as a common genetic risk factor in venous thromboembolism. The purpose of this study was to provide a further frequency value for 1691G>A FV in Poland and to collate summary data from Central (Poland, Czech, Slovakia), Eastern (Russia, Belarus, Ukraine) and South-Eastern (Slovenia, Croatia, Bosnia and Herzegovina, Serbia, Montenegro, Macedonia, Bulgaria) European countries. For this purpose in 2007 the 1691G>A FV variant was analyzed by polymerase chain reaction-restriction fragment length polymorphism from DNA collected in 2005-2006. We studied 650 subjects: 400 newborns and 250 older individuals (mean age 46.1 y) from Poland and compared results with reports from other countries, as well as with the frequency trend of 845G>A HFE across South-Eastern European countries using centroid cities. From our 1691G>A FV study we identified 626 GG homozygotes, 23 GA heterozygotes, and 1 AA homozygote (n = 650), giving an A allele frequency of 1.9%, and a summed frequency value for Poland of 2.0% (n = 1588); the frequency in Central European countries was 3.9% (n = 4559), mostly due to the high value in the Czech Republic: 5.1% (n = 2819); the South-Eastern European countries had 2.5% (n = 2410). Among the Eastern European countries the 1691G>A FV allele frequency was 1.9% (n=791), between the South-Eastern and Eastern European countries there was no significant difference (p=0.17). We confirm that the 1691G>A FV allele frequency in Poland, as well as other countries compared, is significantly lower than that in Czech.

Prevalence of chronic hepatitis B and hepatitis C among first time blood donors in Northeast Bosnia and Herzegovina: an estimate of prevalence in general population.

BACKGROUND: Data on the epidemiology of hepatitis B and C in Bosnia and Herzegovina (B&H) are lacking. OBJECTIVES: To assess the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in blood samples of first time blood donors in a well-defined region of B&H. Our secondary goal was to estimate the prevalence of HBsAg and anti-HCV in the general population of the same region. PATIENTS AND METHODS: We evaluated 8196 blood samples for the presence of HBsAg and/or anti-HCV, adjusted for differences in gender, and used the ratio estimation method to determine the prevalence in the general population. RESULTS: We analyzed 1263 (15.4%) female and 6933 (84.6%) male blood donors (male-to-female ratio: 5.49 to 1). The adjusted prevalence of HBsAg among blood donors was 0.787% (95% CI = 0.535-1.038), while the prevalence of anti-HCV was 0.267% (95% CI = 0.016-0.519). There was no difference in the prevalence of HBsAg or anti-HCV between men and women. We estimate that the prevalence of HBsAg and anti-HCV in the general population is 1.057% to 1.535% and 0.29% to 0.89%, respectively. CONCLUSIONS: The prevalence of HBsAg and anti-HCV among blood donors suggests that our region has low endemicity for both hepatitis B and hepatitis C.

Biochemical and ultrasound parameters may help predict the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with a firm clinical and biochemical suspicion for choledocholithiasis.

BACKGROUND: Prediction of the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected choledocholithiasis (CDL) remains a challenging task. AIMS: We aimed to evaluate the predictive value of biochemical and ultrasound parameters and to create a corresponding model for prediction of the need for therapeutic ERCP. METHODS: 203 consecutive patients referred to our center due to a firm clinical and/or biochemical suspicion for CDL. All patients underwent ERCP. Biochemical and ultrasound variables were analyzed. RESULTS: The sample was divided into testing group (103; 50.7%) and validation group (100; 49.3%) which did not differ in their baseline characteristics. Elevated gamma glutamil transaminase (GGT), common bile duct (CBD) diameter and presence of hyperechoic structures in CBD were found to be significant predictors for presence of CBD stones on ERCP (p<0.05) in the testing group. We used these variables to construct a predictive model for the presence of CBD stones on ERCP. The model was tested on a second, validation group of patients using ROC analysis with the area under the ROC curve of 0.81 (%95 CI=0.75-0.86; p<0.001). We identified a threshold (0.86) above which, patients had a high probability (93.1%) for the need for interventional ERCP. CONCLUSION: Our predictive model may help predict the need for therapeutic ERCP in patients with a suspicion for choledocholithiasis.

Circulating cytokines reflect mucosal inflammatory status in patients with Crohn's disease.

BACKGROUND: There is a great need for a simple activity assessment tool that can reliably predict activity in patients with Crohn's disease (CD). AIM: To investigate the relationship between serum cytokines and endoscopic activity of CD using Crohn's Disease Endoscopic Index of Severity (CDEIS) as a gold standard. METHODS: We prospectively evaluated 32 firmly established CD patients using ileocolonoscopy, CDEIS score, and Crohn's Disease Activity Index (CDAI) score. Blood samples for cytokine analysis were obtained 1 day prior to procedure. RESULTS: The correlation between CDEIS and CDAI was moderate (r = 0.43; P = 0.01); however, the correlation between CDEIS and inflammatory cytokines was excellent, with the highest coefficients for tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) (r = 0.96 and r = 0.96, respectively; P < 0.001). CDEIS and anti-inflammatory cytokines were correlated nonlinearly (power function). We identified two separate models for predicting CDEIS value, based on the best performing pro-inflammatory [CDEIS = 0.445 x (IL-6) - 5,143] and anti-inflammatory [CDEIS = 27.478 x (IL-10)(-0.71)] cytokines. Both IL-6 and IL-10 models had high adjusted R(2) values (0.916 and 0.954, respectively). IL-6 had excellent diagnostic accuracy for detecting patients with CDEIS >7 (active disease), with area under the receiver operating characteristic (ROC) curve of 1.0 [95% confidence interval (CI) = 0.89-1.0; P < 0.001]. CONCLUSION: Serum cytokine levels are excellent predictors of endoscopic activity in patients with CD.

Ulcerative colitis in the Tuzla region of Bosnia and Herzegovina between 1995 and 2006: epidemiological and clinical characteristics.

BACKGROUND: Bosnia and Herzegovina (B&H) is one of the Eastern European countries that lacks data on the epidemiology of ulcerative colitis (UC). AIMS: We aimed to assess the epidemiological and clinical characteristics of UC in Tuzla Canton of B&H during a 12-year period (1995-2006). PATIENTS AND METHODS: We retrospectively evaluated hospital records of both UC inpatients and outpatients residing in Tuzla Canton of B&H (total of 496 280 inhabitants) between 1995 and 2006. Patients that firmly satisfied the diagnostic criteria for UC were included in the study. Incidence rates were calculated with age standardization using European population standards. Trends in incidence were evaluated as moving 3-year averages. RESULTS: During the observed period, 214 patients met the diagnostic criteria for UC. The average age-standardized incidence was found to be 3.43/10 inhabitants [95% confidence interval (CI) = 2.97-3.89], ranging from 0.22 to 7.44 per 10. The mean annual crude incidence in the last 5 years of study (2002-2006) was 5.55/10 (95% CI = 4.63-6.48). The prevalence of UC during the observed period was found to be 43.1/10 (95% CI = 37.3-48.8). The incidence of UC increased dramatically from the average of 1.01/10 in the period between 1995 and 1997 to 6.04/10 between 2004 and 2006, as did the number of colonoscopies performed, from 29 in 1995 to 850 in 2006. The average yearly incidence of confirmed UC cases detected on colonoscopy was 5.56 per 100 colonoscopies per year (95% CI = 4.81-6.30) and only 3.92 per 100 colonoscopies (95% CI = 3.26-4.57) in the last 5 years of the observed period. CONCLUSION: Tuzla Canton of B&H is a region with an increasing incidence of UC, which is most likely a direct consequence of a wider use of colonoscopy. We believe that in the next few years, the incidence of UC in this region will probably reach the annual incidence rate of 6 per 10 inhabitants.

Risk factors for intrafamilial spread of hepatitis B in northeastern Bosnia and Herzegovina.

BACKGROUND: Accurate estimations of hepatitis B virus transmission risk for any region in Bosnia and Herzegovina are not clearly established. We aimed to determine levels of risk associated with intrafamilial transmission of hepatitis B infection within families in our region. PATIENTS AND METHODS: Family members of 81 chronic carriers of hepatitis B surface antigen (>6 months positive and considered as index case) were tested for hepatitis B markers. For family members, we recorded their age, sex, and family relationship to the index case, and vaccination status. RESULTS: The proportion of HBsAg positive family members was 25/207 (12.1%), while the proportion of family members with evidence of exposure to HBV was 80/207 (38.6%). Only 17/207 (8.2%) family members had evidence of past HBV vaccination. Age was found to be a significant predictor of HBV exposure of family members (odds ratio 1.05, 95% CI 1.03-1.07, P<.001). In a multivariate analysis, HBsAg positivity was associated with a female index case (odds ratio 11.31, 95% CI 3.73-34.32, P<.001), HBeAg positivity in the index case (odds ratio 5.56, 95% CI 1.80-17.23, P<.005) and being a mother of the index case (odds ratio 9.82, 95% CI 2.43-39.68, P<.005). A female index case (odds ratio 4.87, 95% CI 2.21-10.72, P<.001), HBeAg positivity in the index case (odds ratio 3.22, 95% CI 1.15-9.00, P<.05) and being a mother of the index case (odds ratio 3.72, 95% CI 1.19-11.64, P<.05) were also risk factors for HBV exposure among family members. The combination of HBeAg positivity and female index case was a significant predictor for HBsAg positivity of family members (odds ratio 70.39, 95% CI 8.20-604.61, P<.001). CONCLUSIONS: Children of HBeAg positive mothers are at highest risk for becoming chronic carriers themselves and generally, the combination of female sex and HBeAg positivity dramatically increases the chances of HBV transmission within the family.