Chronic viral hepatitis and risk of lymphoid malignancies: A retrospective twelve-year population-based cohort study in Côte d’Or,France

BackgroundThe association between hepatitis C infection and lymphoid malignancies is still a matter of debate. The hypothesis of a relationship between hepatitis B and lymphoid neoplasms is more recent and has been far less thoroughly explored.AimThe aim of this study was to evaluate the association between hepatitis C and B infections and B cell non-Hodgkin and Hodgkin lymphomas.MethodsWe took advantage of the co-existence in the French administrative area of Côte d’Or of two specialized registries – one for viral hepatitis and one for haematological diseases – to conduct a population-based, cohort study covering a 12-year period. The databases were anonymized and then linked using a probabilistic model.ResultsThere were 8234 person-years at risk in the hepatitis C cohort and 2784 in the hepatitis B cohort. We found 6 cases of non-Hodgkin lymphoma in the hepatitis C cohort, resulting in an overall adjusted standardized incidence ratio of 3.42 (CI: 1.25–7.45). Three of these 6 cases were diffuse-large-B-cell-lymphoma. Cirrhosis was associated with a higher risk of non-Hodgkin lymphoma in the hepatitis C cohort (relative risk = 8.4, p < 0.01, using a Poisson regression). We found one case of chronic lymphocytic leukaemia amongst the hepatitis B carriers.ConclusionHepatitis C carriers are at a higher risk of developing non-Hodgkin lymphoma than the general population. The role of cirrhosis and the association between hepatitis B and lymphoid malignancies deserve to be further assessed.     

TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia

Background

Acquired somatic deletions and loss-of-function mutations in one or several codons of the TET2 (Ten-Eleven Translocation-2) gene were recently identified in hematopoietic cells from patients with myeloid malignancies, including myeloproliferative disorders and myelodys-plastic syndromes. The present study was designed to determine the prevalence of TET2 gene alterations in chronic myelomonocytic leukemias.

Design and Methods

Blood and bone marrow cells were collected from 88 patients with chronic phase chronic myelomonocytic leukemia and from 14 with acute transformation of a previously identified disease. Polymerase chain reaction analysis and direct sequencing were used to sequence exons 3 to 11 of the TET2 gene. Annotated single nucleotide polymorphisms were excluded. Survival curves were constructed by the Kaplan-Meier method.

Results

We detected TET2 mutations in 44 of 88 (50%) patients with chronic myelomonocytic leukemia, which suggests that TET2 gene mutations are especially frequent in this myeloid disease. A TET2 gene alteration was identified in 18 of the 43 patients studied at diagnosis and was associated with a trend to a lower overall survival rate; confining the analysis to the 29 patients with chronic myelomonocytic leukemia-1, according to the WHO classification, the difference in overall survival between patients with or without TET2 gene mutations became statistically significant.

Conclusions

TET2 gene alterations are more frequent in chronic myelomonocytic leukemia than in other subgroups of hematopoietic diseases studied so far and could negatively affect the patients’ outcome. The striking association between TET2 gene alterations and monocytosis, already observed in patients with systemic mastocytosis, could indicate a negative role of TET2 in the control of monocytic lineage determination.     

Alcohol use and sexual risks for HIV infection among men and women receiving sexually transmitted infection clinic services in Cape Town, South Africa

OBJECTIVE: To examine the association of alcohol use and sexual risks for HIV infection in South Africa. METHOD: 149 men and 78 women receiving sexually transmitted infection (STI) clinic services in Cape Town, South Africa, completed measures of demographic characteristics, sexual behaviors, HIV risk reduction skills and substance use, including global measures (e.g., Alcohol Use Disorders Identification Test [AUDIT]) and situational measures of alcohol use. RESULTS: 52% of men (n = 72) and 17% of women (n = 13) indicated problem drinking (AUDIT score > or = 9). Problem drinking was associated with greater numbers of sex partners in the past month, history of condom failures and lifetime history of having an STI, as well as lower rates of practicing risk reduction skills. In a separate analysis controlling for global use of alcohol indexed by AUDIT scores, we found that alcohol use in sexual contexts was associated with greater numbers of sex partners, higher rates of unprotected intercourse and condom failures. CONCLUSIONS: Findings from this initial study of alcohol use and sexual risks in South Africa parallel those from other countries in sub-Saharan Africa. Although limited to STI clinic patients, the results suggest that effective HIV risk reduction interventions will require attention to alcohol use, particularly among South Africans at highest risk for HIV infection.     

The HLA linked iron loading gene in an Afrikaner population.

The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape.     

Is the management of hepatitis C patients appropriate? A population‐based study

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.     

Prevalence of goitre and urinary iodine status of primary-school children in Lesotho

OBJECTIVE: To estimate the prevalence of goitre, urinary iodine status, coverage of supplementation of iodized oil capsules, and current use of iodized salt in children in Lesotho. METHODS: Cross-sectional study of children from 50 primary schools in Lesotho. Thyroid glands of children aged 8-12 years were measured by palpation and graded according to the WHO, UNICEF, and the International Council for the Control of Iodine Deficiency's (ICCIDD) joint criteria. The use of iodized oil capsules was determined by a structured questionnaire and verified with the children's health booklets. Iodine content of household salt samples was analysed. Casual urine samples were analysed for urinary iodine. FINDINGS: Median urinary iodine concentrations of 26.3 microg/l (range 22.3-47.9 microg/l) indicated moderate iodine deficiency. More children in the mountains than in the lowlands were severely iodine deficient (17.7% vs 1.9%). Adjusted prevalence of goitre (4.9%) increased with age, was higher in girls than boys, and ranged from 2.2% to 8.8% in the different districts; this indicated no public health problem. Overall, 94.4% of salt samples were iodized, and coverage of supplementation with iodized oil capsules was 55.1%. CONCLUSION: Mild-to-moderate iodine deficiency exists in Lesotho. Iodine deficiency was more severe in the mountains than the lowlands and is still a concern for public health. Use of iodized salt coupled with iodized oil supplementation effectively controls iodine deficiency disorders. Effective monitoring programmes would ensure the use of adequately iodized salt throughout Lesotho and serve to evaluate progress towards optimal iodine nutrition. Iodized oil capsule supplementation should continue in the mountains.     

Coronary risk factor screening in three rural communities. The CORIS baseline study

A three-community study of rural Afrikaans-speaking Whites in the south-western Cape revealed that the major reversible risk factors hypercholesterolaemia, hypertension and smoking, as well as 'minor' factors such as inactivity, obesity, hyperuricaemia, coronary-prone behaviour and the irreversible risk factors of chest pain, ischaemic changes on the ECG and a family history of ischaemic heart disease (IHD), were exceedingly common. Singly or in combination, the major risk factors were present in the great majority of the study population after the age of 44 years. The interaction of high levels of lifestyle-induced risk factors with constitutional predisposition could adequately explain any excess risk of IHD in the Afrikaans-speaking community. The almost universal risk factor prevalence in this study has major implications for any preventive strategy.