An increase in the aging population is an impending problem. A large cohort study was carried out to determine the influence of aging and other factors on hepatocarcinogenesis in patients treated with interferon. Biopsy-proven 2547 chronic hepatitis C patients registered at our referral center since 1992 were included. Of these, 2166 were treated with interferon-based therapy. Incidences of hepatocellular carcinoma (HCC) associated with interferon were analyzed by Kaplan-Meier and person-years methods for an average follow-up of 7.5 years. Factors associated with HCC risk were determined by Cox proportional hazard analysis. HCC developed in 177 interferon-treated patients. The risk for HCC depended on age at primary biopsy and increased more than 15-fold after 65 years of age. Even when stratified by stage of fibrosis, the cumulative and annual incidences of HCC were significantly higher in older patients than in younger patients (P < 0.001) at the same stage of fibrosis, except for cirrhosis. Progression of fibrosis over time was significantly accelerated in older patients. The impact of viral eradication on HCC prevention was less significant in older patients than in younger patients. Multivariate analysis confirmed that age, gender, liver fibrosis, liver steatosis, total cholesterol level, fasting blood sugar level, baseline and postinterferon alpha-fetoprotein level, and virological response to interferon were independent risk factors associated with HCC. Aging was the strongest risk factor for a nonvirological response to interferon-based antiviral therapy. Conclusion: Elderly patients are at a higher risk for HCC. Hepatitis C viral eradication had a smaller effect on hepatocarcinogenesis in older patients. Patients should therefore be identified at an earlier age and treatment should be initiated. (HEPATOLOGY 2010;52:518-527) P rimary liver cancer is the third most common cause of cancer mortality worldwide, 1 and hepatocellular carcinoma (HCC) is one of the most frequent primary liver cancers.2,3 Infection with hepatitis C virus (HCV) is a common cause of chronic hepatitis, which progresses to HCC in many patients. 4 The prevalence of older patients has been increasing in Japan, and this is an impending problem in other countries where viral spread has occurred more recently. 5 The number of Americans older than 65 years is expected to double by the year 2030. 6 In Western Europe, people older than 65 years already constitute 15%-18% of the population 7 ; thus, aging patient who is chronically infected with HCV is
in Koshu City, Japan, and their mothers. Maternal smoking during early pregnancy was the exposure studied. Main outcome measures: Childhood body mass index (BMI) and BMI z-score trajectories of the children born to the smoking and non-smoking mothers by gender. Multilevel analysis that includes both individual and age as different-level variables was used for statistical analyses. Results: The participating mothers delivered 1619 babies during the study period. Birth weight and anthropometric data were collected from 1603 (at birth, 99.0%), 1358 (at age 3, 83.9%), 1248 (at age 5, 77.1%), 1270 (at age 7-8, 78.4%) and 1274 (at age 9-10, 78.7%) of these children. The mean birth weight of both the male and female children whose mothers had smoked during pregnancy was significantly low compared with those born to non-smoking mothers (Po0.01). However, the childhood BMI at each subsequent checkup age significantly increased only among the male children born to the smoking mothers. Moreover, this increase was continuously observed after 3 years of age. The results of BMI z-score analysis were also similar to these of BMI analysis. Conclusions: Smoking by pregnant women decreases the infant birth weight irrespective of gender but increases childhood weight gain especially by male children. The results might be valuable to explore the mechanism of fetal programming.
BackgroundLow birth weight (LBW) infants do not form a homogeneous group; LBW can be caused by prematurity or poor fetal growth manifesting as small for gestational age (SGA) infants or intrauterine growth retardation. We aimed to clarify the relationship of maternal smoking with both SGA and preterm LBW infants.MethodsThe study population comprised pregnant women who registered at the Koshu City between January 1, 1995, and December 31, 2000, and their children. We performed multivariate analyses using multiple logistic regression models to clarify the relationship of maternal smoking during pregnancy with the SGA outcome and preterm birth in LBW infants.ResultsIn this study period, 1,329 pregnant women responded to questionnaires, and infant data were collected from 1,100 mothers (follow-up rate: 82.8%). The number of LBW infants was 81 (7.4%). In this cohort, maternal smoking during early pregnancy was associated with LBW and the SGA outcome. Maternal smoking during early pregnancy was a risk factor for LBW with SGA outcome and for LBW with full-term birth. However, it was not a risk factor for LBW with appropriate weight for gestational age (AGA) and LBW with preterm birth.ConclusionThese results suggested that LBW with AGA and LBW with preterm birth were associated with other risk factors that were not considered in this study, such as periodontal disease. For the prevention of LBW, not only abstinence from smoking during pregnancy but also other methods such as establishing a clinical setting should be adopted.
Hepatic steatosis is a significant risk factor for development of HCC in chronic hepatitis C independent of other known risk factors, which suggest the possibility that amelioration of hepatic steatosis may prevent hepatocarcinogenesis.
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