Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis.

The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-tuberculin IgG antibody levels mediate the anergy described herein, which could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such anti-tuberculin IgG antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with tuberculin. In this regard, future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG.

Treatment evolution in high-risk congenital diaphragmatic hernia: ten years' experience with diaphragmatic agenesis.

OBJECTIVE: The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm. SUMMARY BACKGROUND DATA: CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity. METHODS: Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death or hospital discharge. RESULTS: A total of 1,569 patients with CDH were seen between January 1995 and December 2004 in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and underwent repair. The overall survival for all patients was 68%, while survival was 54% in patients with agenesis. When patients with diaphragmatic agenesis from the first 2 years were compared with similar patients from the last 2 years, there was significantly less use of ECMO (75% vs. 52%) and an increased use of inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved survival in patients with agenesis from 47% in the first 2 years to 59% in the last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital stays compared with patients without agenesis (median, 68 vs. 30 days). For the last 2 years of the study, 36% of the patients with agenesis were discharged on tube feedings and 22% on oxygen therapy. CONCLUSIONS: There has been a change in the management of infants with CDH with less frequent use of ECMO and a greater use of iNO in high-risk patients with a potential improvement in survival. However, the mortality, hospital length of stay, and morbidity in agenesis patients remain significant.

Comprehensive environmental study in high risk areas for cancer patients comparing air and water Aspergillus species samples

Background. Nosocomial invasive aspergillosis (a highly fatal disease) is an increasing problem for immunocompromised patients. Aspergillus spp. can be transmitted via air (most commonly) and by water. ^ The hypothesis for this prospective study was that there is an association between patient occupancy, housekeeping practices, patients, visitors, and Aspergillus spp. loading. Rooms were sampled as not terminally cleaned (dirty) and terminally cleaned (clean). The secondary hypothesis was that Aspergillus spp. positive samples collected from more than one sampling location within the same patient room represent the same isolate. ^ Methods. Between April and October 2004, 2873 environmental samples (713 air, 607 water, 1256 surface and 297 spore traps) were collected in and around 209 “clean” and “dirty” patient rooms in a large cancer center hospital. Water sources included aerosolized water from patient room showerheads, sinks, drains, and toilets. Bioaerosol samples were from the patient room and from the running shower, flushing toilet, and outside the building. The surface samples included sink and shower drains, showerheads, and air grills. Aspergillus spp. positive samples were also sent for PCR, molecular typing (n = 89). ^ Results. All water samples were negative for Aspergillus spp. There were a total of 130 positive culturable samples (5.1%). The predominant species found was Aspergillus niger. Of the positive culturable samples, 106 (14.9%) were air and 24 (3.8%) were surface. There were 147 spore trap samples, and 49.5% were positive for Aspergillus/Penicillum spp. Of the culturable positive samples sent for PCR, 16 were indistinguishable matches. There was no significant relationship between air and water samples and positive samples from the same room. ^ Conclusion. Primarily patients, visitors and staff bring the Aspergillus spp. into the hospital. The high number of A. niger samples suggests the spores are entering the hospital from outdoors. Eliminating the materials brought to the patient floors from the outside, requiring employees, staff, and visitors to wear cover up over their street clothes, and improved cleaning procedures could further reduce positive samples. Mold strains change frequently; it is probably more significant to understand pathogenicity of viable spores than to commit resources on molecular strain testing on environmental samples alone. ^

School screening for tuberculosis in high risk areas of Texas

Screening for latent tuberculosis infection (LTBI) is an integral component of an effective tuberculosis control strategy, but one that is often relegated to the lowest priority. In a state with higher than national average rates of tuberculosis, due consideration should be given to LTBI screening. Recent large scale contact investigations in the middle school of Del Rio, Texas, raised questions about the status of school screening for LTBI. An evidence based approach was used to evaluate school screening in high risk areas of Texas. A review of the literature revealed that the current recommendations for LTBI screening in children is based on administration of a risk factor questionnaire that should be based on the four main risk factors for LTBI in children that have been identified. Six representative areas in Texas were identified for evaluation of the occurrence of contact investigations in schools for the period of 2006 to 2009 and any use of school screening programs. Of the five reporting areas that responded, only one utilized a school screening program; this reporting area had the lowest percentage of contact investigations occurring in schools. Contact investigations were most common in middle schools and least common in elementary schools. In metropolitan areas, colleges represented up to 42.9% of contact investigations. The number of contact investigations has increased from 2006 to 2008. This report represents a small sample, and further research into the frequency, distribution and risk for contact investigations in schools and the efficacy of screening programs should be done. ^

Secondary data analysis of lead screening compliance in high-risk children

Introduction. Despite the ban of lead-containing gasoline and paint, childhood lead poisoning remains a public health issue. Furthermore, a Medicaid-eligible child is 8 times more likely to have an elevated blood lead level (EBLL) than a non-Medicaid child, which is the primary reason for the early detection lead screening mandate for ages 12 and 24 months among the Medicaid population. Based on field observations, there was evidence that suggested a screening compliance issue. Objective. The purpose of this study was to analyze blood lead screening compliance in previously lead poisoned Medicaid children and test for an association between timely lead screening and timely childhood immunizations. The mean months between follow-up tests were also examined for a significant difference between the non-compliant and compliant lead screened children. Methods. Access to the surveillance data of all childhood lead poisoned cases in Bexar County was granted by the San Antonio Metropolitan Health District. A database was constructed and analyzed using descriptive statistics, logistic regression methods and non-parametric tests. Lead screening at 12 months of age was analyzed separately from lead screening at 24 months. The small portion of the population who were also related were included in one analysis and removed from a second analysis to check for significance. Gender, ethnicity, age of home, and having a sibling with an EBLL were ruled out as confounders for the association tests but ethnicity and age of home were adjusted in the nonparametric tests. Results. There was a strong significant association between lead screening compliance at 12 months and childhood immunization compliance, with or without including related children (p<0.00). However, there was no significant association between the two variables at the age of 24 months. Furthermore, there was no significant difference between the median of the mean months of follow-up blood tests among the non-compliant and compliant lead screened population for at the 12 month screening group but there was a significant difference at the 24 month screening group (p<0.01). Discussion. Descriptive statistics showed that 61% and 56% of the previously lead poisoned Medicaid population did not receive their 12 and 24 month mandated lead screening on time, respectively. This suggests that their elevated blood lead level may have been diagnosed earlier in their childhood. Furthermore, a child who is compliant with their lead screening at 12 months of age is 2.36 times more likely to also receive their childhood immunizations on time compared to a child who was not compliant with their 12 month screening. Even though there was no statistical significant association found for the 24 month group, the public health significance of a screening compliance issue is no less important. The Texas Medicaid program needs to enforce lead screening compliance because it is evident that there has been no monitoring system in place. Further recommendations include a need for an increased focus on parental education and the importance of taking their children for wellness exams on time.^

Effectiveness of Community Case Management in Family Risk Reduction

This study evaluated a modified home-based model of family preservation services, the long-term community case management model, as operationalized by a private child welfare agency that serves as the last resort for hard-to-serve families with children at severe risk of out-of-home placement. The evaluation used a One-Group Pretest-Posttest design with a modified time-series design to determine if the intervention would produce a change over time in the composite score of each family's Child Well-Being Scales (CWBS). A comparison of the mean CWBS scores of the 208 families and subsets of these families at the pretest and various posttests showed a statistically significant decrease in the CWBS scores, indicating decreased risk factors. The longer the duration of services, the greater the statistically significant risk reduction. The results support the conclusion that the families who participate in empowerment-oriented community case management, with the option to extend service duration to resolve or ameliorate chronic family problems, have experienced effective strengthening in family functioning.

The angiotensin-converting enzyme insertion/deletion polymorphism and its associations with carotid artery wall thickness and coronary heart disease: The atherosclerosis risk in communities study

Coronary heart disease (CHD) is the leading cause of death in the United States. Recently, renin-angiotensin system (RAS) was found associated with atherosclerosis formation, with angiotensin II inducing vascular smooth muscle cell growth and migration, platelet activation and aggregation, and stimulation of plasminogen activator inhibitor-1. Angiotensin II is converted from angiotensin I by angiotensin I-converting enzyme (ACE) and this enzyme is mainly genetically determined. The ACE gene has been assigned to chromosome 17q23 and an insertion/deletion (I/D)polymorphism has been characterized by the presence/absence of a 287 bp fragment in intron 16 of the gene. The two alleles form three genotypes, namely, DD, ID and II and the DD genotype has been linked to higher plasma ACE levels and cell ACE activity.^ In this study, the association between the ACE I/D polymorphism and carotid artery wall thickness measured by B-mode ultrasound was investigated in a biracial sample, and the association between the gene and incident CHD was investigated in whites and if the gene-CHD association in whites, if any, was due to the gene effect on atherosclerosis. The study participants are from the prospective Atherosclerosis Risk in Communities (ARIC) Study, including adults aged 45 to 65 years. The present dissertation used a matched case-control design for studying the associations of the ACE gene with carotid artery atherosclerosis and an unmatched case-control design for the association of the gene with CHD. A significant recessive effect of the D allele on carotid artery thickness was found in blacks (OR = 3.06, 95% C.I: 1.11-8.47, DD vs. ID and II) adjusting for age, gender, cigarette smoking, LDL-cholesterol and diabetes. No similar associations were found in whites. The ACE I/D polymorphism is significantly associated with coronary heart disease in whites, and while stratifying data by carotid artery wall thickness, the significant associations were only observed in thin-walled subgroups. Assuming a recessive effect of the D allele, odds ratio was 2.84 (95% C.I:1.17-6.90, DD vs. ID and II) and it was 2.30 (95% C.I:1.22-4.35, DD vs. ID vs. II) assuming a codominant effect of the D allele. No significant associations were observed while comparing thick-walled CHD cases with thin-walled controls. Following conclusions could be drawn: (1) The ACE I/D polymorphism is unlikely to confer appreciable increase in the risk of carotid atherosclerosis in US whites, but may increases the risk of carotid atherosclerosis in blacks. (2) ACE I/D polymorphism is a genetic risk factor for incident CHD in US whites and this effect is separate from the chronic process of atherosclerosis development. Finally, the associations observed here are not causal, since the I/D polymorphism is in an intron, where no ACE proteins are encoded. ^

Behavioral and psychosocial factors associated with sexual risk in a population of crack cocaine users

The purpose of this dissertation was to examine the relationship between key psychosocial and behavioral components of the Transtheoretical Model and the Theory of Reasoned Action for sexual risk reduction in a population of crack cocaine smokers and sex workers, not in drug treatment. ^ The first study examined the results of an analysis of the association between two principal constructs in the Transtheoretical Model, the processes of change and the stages of change for condom use, in a high risk population. In the analysis of variance for all respondents, the overall F-test revealed that people in different stages have different levels of experiential process use, F(3,317) = 17.79, p = 0.0001 and different levels of behavioral process use, F(3,317) = 28.59, p = .0001. For the experiential processes, there was a significant difference between the precontemplation/contemplation stage, and both the action, and maintenance, stages.^ The second study explored the relationship between the Theory of Reasoned Action “beliefs” and the stages-of-change in the same population. In the analysis of variance for all participants, the results indicate that people in different stages did value the positive beliefs differently, F(3,502) = 15.38, p = .0001 but did not value the negative beliefs differently, F(3,502) = 2.08, p = .10. ^ The third study explored differences in stage-of-change by gender, partner type drug use, and HIV status. Three discriminant functions emerged, with a combined χ2(12) = 139.57, p = <.0001. The loading matrix of correlations between predictors and discriminant functions demonstrate that the strongest predictor for distinguishing between the precontemplation/contemplation stage and the preparation, action, and maintenance stages (first function) is partner type (.962). The loadings on the second discriminant function suggest that once partner type has been accounted for, ever having HIV/AIDS (.935) was the best predictor for distinguishing between the first three stages and the maintenance stage. ^ These studies demonstrate that behavioral change theories can contribute important insight to researchers and program planners attempting to alter HIV risk behavior in high-risk populations. ^

Depressive symptoms and sexual risk behaviors in adolescents

The purpose of this study was to determine whether depression is a factor in explaining the difference in sex behaviors among adolescents with different ethnic backgrounds, family and school contexts. We hypothesize that adolescents with a higher number of depressive symptoms are more likely to engage in sexual risk behaviors than adolescents with fewer depressive symptoms. Further, adolescent depression and sexual behaviors are mediated or moderated by individual characteristics, family and school contexts. ^ Background. large ethnic disparities exist in adolescent engagement in risky sexual behaviors, yet, there is little in the literature that explains these disparities. Studies of sexual behavior of youths abound; yet, there is little literature on the prevalence and correlates of depression or the association between depression and sexual behaviors among different ethnic groups. Objectives. (1) To determine ethnic differences in the prevalence of depressive symptoms using data collected through the National Longitudinal Study of Adolescent Health (Add Health). (2) To determine predictors of sex risk behaviors among adolescents, including the role of depression. (3) To identify predictors of depression among these adolescents. Methods. Add Health data from wave 1 and wave 2 interviews of 7th–12th graders were analyzed using multivariate models constructed with both depression and sexual behavior as outcome variables. Logistic regression models determined whether and to what extent the independent variables, including depression, sex behaviors, demographic factors, individual and family characteristics, and school context were related to the probability of engaging in risky sexual behaviors. Results. Ethnic differences in depressive symptoms did not persist after demographic and contextual variables were included in the model. Sex behaviors all shared the hypothesized relationship with depressive symptoms. The odds of risky sex behaviors increased as number of depressive symptoms increased. Depression was predicted by marijuana use and having a serious argument with father for males at Wave 1 and by age and future orientation for females. Wave 2 depression was predicted by Wave 1 depression. ^

Parental demographic risk factors and occupational exposure to ionizing radiation for achondroplasia, thanatophoric and autosomal deletions in Texas, 1996--2002

Little is known about the etiology of Achondroplasia (AC), Thanatophoric Dwarfism (TD), and autosomal deletions (CD). These syndromes are due to fully penetrate genetic mutations, yet arise de novo, instead of being inherited. We examined the association between parental demographic characteristics and parental occupations with exposure to ionizing radiation and these birth defects. ^ We conducted a cross-sectional study and two case-control studies using a large database that was created by linking records from Texas Birth Defects Registry, Texas birth certificates and Texas fetal death certificates from 1996 to 2002. The first case-control study was matched on paternal age and examined 73 cases of AC and 43 cases of TD. The second case-control study was unmatched and examined 343 cases of autosomal deletion syndromes. ^ We used a job exposure matrix (JEM) to measure exposures to ionizing radiation in the workplace. This gives an estimate of the intensity and probability of exposure to ionizing radiation for each occupation and industry. ^ The prevalence rate of Achondroplasia, Thanatophoric Dwarfism and autosomal deletions was 0.36 per 10,000, 0.21 per 10,000, and 1.68 per 10,000 births respectively in Texas 1996–2002. ^ Older fathers had a strong increase in the risk of having offspring with AC or TD and a modest increase in the risk of CD. Fathers who were Black or Hispanic were less likely to have infants with AC or TD compared to Whites (adjusted POR=0.61; 95% CI 0.30, 1.26 and 0.44; 95% CI 0.27, 0.88, respectively). Black fathers and Hispanic mothers were also less likely to have infants with CD (adjusted POR=0.54; 95% CI 0.22, 1.35 and 0.62; 95% CI 0.39, 0.97). ^ After adjusting for other parental demographic factors, there was no significant relation between fathers exposure to ionizing radiation in the work place and AC or TD (adjusted OR=0.48; 95% CI 0.19, 1.25) and no significant relation between parental exposure to ionizing radiation in the work place and CD (adjusted OR=1.16; 95% CI 0.73, 1.85). ^ This is the first study to find an association between father's age and TD and CD and paternal race and AC or CD. Parental exposure to radiation for therapeutic or diagnostic indications was not measured, thus it can not be excluded as a cause of these birth defects. ^

Factor H variant Y402H and the prevalence of hypertension and proteinuria: The Atherosclerosis Risk in Communities study

Hypertension is a significant risk factor for cardiovascular disease, which in turn is a major cause of morbidity and mortality worldwide. While the pathogenesis of vascular injury and subsequent end organ damage is complex, there is emerging data to support a role for the complement system in endovascular diseases. The complement Factor H Y402H polymorphism has been associated with a number of vasculopathies, including age-related macular degeneration (AMD), ischemic stroke and myocardial infarction. The current study evaluated the relationship of the Y402H polymorphism with hypertension and microalbuminuria in large the bi-racial Atherosclerosis Risk in Communities (ARIC) study. The Y402H polymorphism was found to be associated with a 48% (p-value 0.042) increase in the risk of developing incident hypertension in African American participants. No significant association was found with the Y402H polymorphism and microalbuminuria. The results from this investigation reveal the first association of the Factor H Y402H polymorphism and an increased risk of incident hypertension in African Americans. ^

Risk factors for encephalitis and death from West Nile virus infection: An analysis of hospitalized cases in Houston, Texas from 2002--2008

We conducted a nested case-control study to determine the significant risk factors for developing encephalitis from West Nile virus (WNV) infection. The purpose of this research project was to expand the previously published Houston study of 2002–2004 patients to include data on Houston patients from four additional years (2005–2008) to determine if there were any differences in risk factors shown to be associated with developing the more severe outcomes of WNV infection, encephalitis and death, by having this larger sample size. A re-analysis of the risk factors for encephalitis and death was conducted on all of the patients from 2002–2008 and was the focus of this proposed research. This analysis allowed for the determination to be made that there are differences in the outcome in the risk factors for encephalitis and death with an increased sample size. Retrospective medical chart reviews were completed for the 265 confirmed WNV hospitalized patients; 153 patients had encephalitis (WNE), 112 had either viral syndrome with fever (WNF) or meningitis (WNM); a total of 22 patients died. Univariate logistic regression analyses on demographic, comorbidities, and social risk factors was conducted in a similar manner as in the previously conducted study to determine the risk factors for developing encephalitis from WNV. A multivariate model was developed by using model building strategies for the multivariate logistic regression analysis. The hypothesis of this study was that there would be additional risk factors shown to be significant with the increase in sample size of the dataset. This analysis with a greater sample size and increased power supports the hypothesis in that there were additional risk factors shown to be statistically associated with the more severe outcomes of WNV infection (WNE or death). Based on univariate logistic regression results, these data showed that even though age of 20–44 years was statistically significant as a protecting effect for developing WNE in the original study, the expanded sample lacked significance. This study showed a significant WNE risk factor to be chronic alcohol abuse, when it was not significant in the original analysis. Other WNE risk factors identified in this analysis that showed to be significant but were not significant in the original analysis were cancer not in remission > 5 years, history of stroke, and chronic renal disease. When comparing the two analyses with death as an outcome, two risk factors that were shown to be significant in the original analysis but not in the expanded dataset analysis were diabetes mellitus and immunosuppression. Three risk factors shown to be significant in this expanded analysis but were not significant in the original study were illicit drug use, heroin or opiate use, and injection drug use. However, with the multiple logistic regression models, the same independent risk factors for developing encephalitis of age and history of hypertension including drug induced hypertension were consistent in both studies.^

Macular edema in Hispanics with non-insulin dependent diabetes mellitus in Starr County, Texas: Prevalence, incidence and risk factors

This project is based on secondary analyses of data collected in Starr County, Texas from 1981 till 1991 to determine the prevalence, incidence and risk factors for macular edema in Hispanics with non-insulin-dependent diabetes in Starr County, Texas. Two studies were conducted. The first study examined the prevalence of macular edema in this population. Of the 310 diabetics that were included in the study 22 had macular edema. Of these 22 individuals 9 had clinically significant macular edema. Fasting blood glucose was found to be significantly associated with macular edema. For each 10 mg/dl increase in fasting blood glucose there was a 1.07 probability of an increase in the risk of having macular edema. Individuals with fasting blood glucose $\ge$200 mg/dl were found to be more than three times at risk of having macular edema compared to those with fasting blood glucose $<$200 mg/dl.^ In the second study the incidence and the risk factors that could cause macular edema in this Hispanic population were examined. 240 Hispanics with non-insulin-dependent diabetes mellitus and without macular edema were followed for 1223 person-years. During the follow-up period 27 individuals developed macular edema (2.21/100 person-years). High fasting blood glucose and glycosylated hemoglobin were found to be strong and independent risk factors for macular edema. Participants taking insulin were 3.9 times more at risk of developing macular edema compared to those not taking insulin. Systolic blood pressure was significantly related to macular edema, where each 10 mmHg increase in systolic blood pressure was associated with a 1.3 increase in the risk of macular edema.^ In summary, this study suggests that hyperglycemia is the main underlying factor for retinal pathological changes in this diabetic population, and that macular edema probably is not the result of sudden change in the blood glucose level. It also determined that changes in blood pressure, particularly systolic blood pressure, could trigger the development of macular edema.^ Based on the prevalence reported in this study, it is estimated that 35,500 Hispanic diabetics in the US have macular edema. This imposes a major public health challenge particularly in areas with high concentration of Mexican Americans. It also highlights the importance of public health measures directed to Mexican Americans such as health education, improved access to medical care, and periodic and careful ophthalmologic examination by ophthalmologists knowledgeable and experienced in the management of diabetic macular edema. ^

Frequencies and risk factors for bisphosphonate-related osteonecrosis of the jaw in cancer patients: A matched case-control study

Bisphosphonates represent a unique class of drugs that effectively treat and prevent a variety of bone-related disorders including metastatic bone disease and osteoporosis. High tolerance and high efficacy rates quickly ranked bisphosphonates as the standard of care for bone-related diseases. However, in the early 2000s, case reports began to surface that linked bisphosphonates with osteonecrosis of the jaw (ONJ). Since that time, studies conducted have corroborated the linkage. However, as with most disease states, many factors can contribute to the onset of disease. The aim of this study was to determine which comorbid factors presented an increased risk for developing ONJ in cancer patients.^ Using a case-control study design, investigators used a combination of ICD-9 codes and chart review to identify confirmed cases of ONJ at The University of Texas M. D. Anderson Cancer Center (MDACC). Each case was then matched to five controls based on age, gender, race/ethnicity, and primary cancer diagnosis. Data querying and chart review provided information on variables of interest. These variables included bisphosphonate exposure, glucocorticoids exposure, smoking history, obesity, and diabetes. Statistical analysis was conducted using PASW (Predictive Analytics Software) Statistics, Version 18 (SPSS Inc., Chicago, Illinois).^ One hundred twelve (112) cases were identified as confirmed cases of ONJ. Variables were run using univariate logistic regression to determine significance (p < .05); significant variables were included in the final conditional logistic regression model. Concurrent use of bisphosphonates and glucocorticoids (OR, 18.60; CI, 8.85 to 39.12; p < .001), current smokers (OR, 2.52; CI, 1.21 to 5.25; p = .014), and presence of diabetes (OR, 1.84; CI, 1.06 to 3.20; p = .030) were found to increase the risk for developing ONJ. Obesity was not associated significantly with ONJ development.^ In this study, cancer patients that received bisphosphonates as part of their therapeutic regimen were found to have an 18-fold increase in their risk of developing ONJ. Other factors included smoking and diabetes. More studies examining the concurrent use of glucocorticoids and bisphosphonates may be able to strengthen any correlations.^

A case-control study of hepatitis C virus and its interaction with hepatitis B virus on the development of hepatocellular carcinoma in the USA

Objective. The aim of this study was to assess the independent risk of hepatitis C virus (HCV) infection in the development of hepatocellular carcinoma (HCC). The independent risk of hepatitis B virus (HBV), its interaction with hepatitis C virus and the association with other risk factors were examined.^ Methods. A hospital-based case-control study was conducted between January 1994 and December 1995. We enrolled 115 pathologically confirmed HCC patients and 230 nonliver cancer controls, who were matched by age ($\pm$5 years), gender, and year of diagnosis. Both cases and controls were recruited from The University of Texas M. D. Anderson Cancer Center at Houston. The risk factors were collected through personal interviews and blood samples were tested for HCV and HBV markers. Univariate and multivariate analyses were performed through conditional logistic regression.^ The prevalence of anti-HCV positive is 25.2% in HCC cases compared to 3.0% in controls. The univariate analysis showed that anti-HCV, HBsAg, alcohol drinking and cigarette smoking were significantly associated with HCC, however, family history of cancer, occupational chemical exposure, and use of oral contraceptive were not. Multivariate analysis revealed a matched odds ratio (OR) of 10.1 (95% CI 3.7-27.4) for anti-HCV, and an OR of 11.9 (95% CI 2.5-57.5) for HBsAg. However, dual infection of HCV and HBV had only a thirteen times increase in the risk of HCC, OR = 13.9 (95% CI 1.3-150.6). The estimated population attributable risk percent was 23.4% for HCV, 12.6% for HBV, and 5.3% for both viruses. Ever alcohol drinkers was positively associated with HCC, especially among daily drinkers, matched OR was 5.7 (95% CI 2.1-15.6). However, there was no significant increase in the risk of HCC among smokers as compared to nonsmokers. The mean age of HCC patients was significantly younger among the HBV(+) group and among the HCV(+)/HBV(+) group, when compared to the group of HCC patients with no viral markers. The association between past histories of blood transfusion, acupuncture, tattoo and IVDU was highly significant among the HCV(+) group and the HBV(+)/HCV(+) group, as compared to HCC patients with no viral markers. Forty percent of the HCC patients were pathologically or clinically diagnosed with liver cirrhosis. Anti-HCV(+) (OR = 3.6 95% CI 1.5-8.9) and alcohol drinking (OR = 2.7 95% CI 1.1-6.7), but not HBsAg, are the major risk factors for liver cirrhosis in HCC patients.^ Conclusion. Both hepatitis B virus and hepatitis C virus were independent risk factors for HCC. There was not enough evidence to determine the interaction between both viruses. Only daily alcoholic drinkers showed increasing risk for HCC development, as compared to nondrinkers. ^