Roberta Chiesa

Case‐control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: The role of HCV genotypes and the synergism with hepatitis B virus and alcohol

We performed a case‐control study to evaluate the risk of hepatocellular carcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly diagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by clinically evident hepatic disease admitted to the 2 main hospitals in Brescia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patients (68%), genotype 2 in 36 (29.5%) and genotype 1a in 3 (2.5%). Among the controls, 15 were infected with genotype 1b and 15 with type 2. Analysis of HCV envelope 1 nucleotide sequence among 25 cases and 8 controls infected with genotype 2 showed subtype 2c in 96% of cases and in all controls, and subtype 2a in 1 HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confidence interval (CI): 15.8–44], and it was higher for genotype 1b (OR = 34.2) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5–87.1) when the HBV markers were all negative and 132 (15.3–890) when HBsAg positivity was present; the OR was 26.1 (95% CI: 12.6–54.0) among subjects with alcohol intake of 0–40 g/day and increased to 62.6 (23.3–168) and 126 (42.8–373) with an alcohol intake of 41–80 and >80 g/day, respectively. In conclusion, synergism was found between HCV infection and HBV infection and alcohol intake in causing HCC. Int. J. Cancer 81:695–699, 1999.

A case-control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy

Objectives: We carried out a case–control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC).Methods: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity.Results: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2–4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.6–1.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6–6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake.Conclusions: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.

Smoking among High School Students in 10 Italian Towns: Patterns and Covariates

The associations between tobacco smoking and demographic, socioeconomic, environmental, and behavioral factors among adolescents were investigated by administering an anonymous questionnaire to 5,221 ninth (aged 14-15 years) and 4,154 thirteenth grade (aged 18-19 years) students in 10 Italian towns. Using logistic regression analysis, both current smoking and experimental smoking were statistically associated with sibling, best friend, and partner smoking, alcohol drinking, and frequency of drunkenness in both grades and sexes. Attitude of parents toward childrens smoking was also found to be associated with the probability of being a current smoker, especially among ninth graders. Parental smoking was associated with current smoking among females only. Socioeconomic factors and level of knowledge of the health consequences of smoking were not associated with either experimental or regular smoking. In conclusion, this survey suggests that social environment plays a fundamental role in both first experimentation with smoking and the process of becoming a regular smoker among adolescents. Students with one or more siblings who smoke, and especially those with best friends and a partner who smoke, were much more likely to have tried smoking and to be current smokers than students without smokers in their environment.

Primary liver cancer in a high-incidence area in North Italy: Etiological hypotheses arising from routinely collected data

The incidence rate for primary liver cancer (PLC) was investigated in the Health Unit of Brescia (about 325,000 inhabitants), North Italy, in the 5-year period 1986–90, in order to ascertain whether there was a high risk for developing the disease in the area as suggested by mortality data. A total of 349 incident cases were observed (male: female ratio =3.4: 1), of which 182 (52.1%) were diagnosed through histology. The cumulative risk was about 5% and 1% in males and females, respectively. The crude incidence rates were 34.5/100,000 in males and 9.4/100,000 in females, and the age-standardized rates were the highest among all those observed in the 9 Italian areas covered by Cancer Registries. Although about half of the cases in males can be attributed to either chronic alcoholic disease or HBV infection or both, further research is needed to investigate the role of known risk factors for PLC in the Health Unit.

Prevalence of GB virus-C/hepatitis G virus infection in patients with cryptogenic chronic liver disease and in patients with primary biliary cirrhosis or Wilson’s disease

Objective:To assess the role of hepatitis G virus (HGV) in cryptogenic chronic liver disease (CLD), we investigated the prevalence of HGV RNA among patients with cryptogenic CLD, patients with nonviral CLD (primary biliary cirrhosis [PBC] and Wilsons disease [WD]) and subjects without clinically evident liver disease (controls).Methods:Ninety patients with cryptogenic CLD (43 with chronic hepatitis, 20 with cirrhosis, and 27 with hepatocellular carcinoma [HCC]), 143 patients with PBC, 22 patients with WD, and 134 controls were recruited. HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and antibodies against HGV E2 protein (anti-E2) by an immunoassay test.Results:HGV RNA was detected in 7.8% of patients with cryptogenic CLD (chronic hepatitis, 9.3%; cirrhosis, 5.0%; HCC, 7.4%), in 2.4% of patients with PBC or WD, and in 2.2% of controls. As a consequence, a positive association of HGV infection with cryptogenic CLD was found (odds ratio, 3.1; 95% confidence interval [CI], 1.0–9.7; p= 0.05). No difference was observed between HGV RNA-positive and -negative patients by age, sex, histology, or liver function tests. Anti-E2 prevalence did not differ between patients with cryptogenic CLD (26.5%), patients with PBC (28.1%), and controls (22.1%). Transfusion history was associated with HGV RNA but not with anti-E2 seropositivity.Conclusions:Although an association was found between cryptogenic CLD and HGV infection, the role of the virus seems far from important, the proportion of cryptogenic CLD attributable to it being only 5.2%.

Alcohol drinking among adolescents from town and mountainous areas in north Italy.

Alcohol consumption was investigated among 9th and 13th grade high school students in the town of Brescia (an urban area) and in the Local Health Unit of Breno, a mountainous area in the province of Brescia. A total of 1364 students from Brescia and 1373 from Breno completed an anonymous questionnaire during school time. In both groups alcohol consumption was greater among 13th graders (modal age: 18 years) and males than 9th graders (modal age: 14 years) and females. Beer was the favourite alcoholic beverage, but wine was the most widely consumed daily beverage: among males, about 8% in grade 9 and 15% in grade 13 drank at least one glass of wine every day. The majority of both 9th and 13th graders had more than one type of alcoholic beverage a week, although many females drank beer only. Total alcohol consumption was higher among the mountainous area students than urban students, especially 9th graders, and greater differences were observed in the consumption of beer with respect to wine. The proportion of male students from Brescia and Breno who consumed more than 6 alcohol units a week were, respectively, 17% and 25% in grade 9 and 36% and 42% in grade 13. A higher prevalence of drunkenness was found among the students from the mountainous area with respect to the urban students, especially males. Among 13th grade males, 42% of students from Brescia and 60% from Breno claimed one or more episodes of drunkenness during the year prior to the interview.

Diagnostic accuracy of primary liver cancer: implications for cancer registration.

Aims and background We evaluated some standardized criteria for classifying incident cases of liver cancer into either primary liver cancer (PLC) or unspecified liver cancer (ULC) on the basis of the diagnostic examinations performed and their results. Methods A pilot hospital-based study (98 cases) was carried out in Verona, northern Italy, with the main aim of assessing the feasibility of the method. The same procedures were subsequently applied in a population-based study (349 cases) in Brescia, northern Italy. Results Diagnosis was made on histologic data in 38.7% and 41.8% of the hospital based and population-based studies, respectively, with a wide variation among different hospitals. The percentage of cases classified as PLC was 78.6% in the hospital-based study and 78.8% in the population-based study. No differences in the proportion of cases attributed to PLC were found according to patients’ age and sex or hospital of admission. The repeatibility of the procedure was assessed by a cross-panel review of 198 cases, and concordance was found in 91.9% of them. Conclusions An operational method for case definition of PLC based on the results of the diagnostic examinations currently performed and some suggestions for cancer registration are proposed.

Liver genotoxic activity of an epoxide derivative of the hepatocarcinogenic β-blocker DL-ZAMI 1305

A single administration of the sex-dependent hepatocarcinogenic beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) induces dose-dependent liver DNA damage, as evaluated by alkaline sucrose gradient analysis, in female but not in male Fisher 344 rats. A single administration of the direct mutagenic epoxide-derivative of DL-ZAMI 1305 3-methyl-2-nitro-1-(2,3-epoxypropoxy)-benzene induces dose-dependent DNA damage in the liver of animals of both sexes. However, also in this case, the genotoxic activity of the compound appears to be significantly higher in female than in male rats. A DNA-damaging capacity similar in the two sexes is instead exerted by DL-ZAMI 1305-unrelated direct mutagens, like N-methyl-N-nitrosourea (MNU) and methyl-methanesulfonate (MMS). The data confirm the sex-dependent susceptibility of rat liver to the genotoxic activity of DL-ZAMI 1305-related molecules, also in the absence of an absolute requirement for a metabolic activation of the compound.