[Is chronic hepatitis C treatment as efficient in the general population as in randomised trials?]. / Le traitement de l'hépatite chronique C est-il aussi efficace dans la population générale que dans les essais randomisés?

AIMS: The aim of this population-based study was to determine the effectiveness of antiviral therapy in non selected chronic hepatitis C patients. METHODS: The study was performed in all new patients with anti-HCV antibodies who had registered in a specialised viral hepatitis registry since 1994 and who lived in the French departments of Côte-d'Or and Doubs (1 005 817 inhabitants). RESULTS: 1251 of the 1508 recorded cases were studied; 262 were treated. Results of treatment were available in 238 cases, 157 were treated with interferon alone and 81 with interferon + ribavirine. Sustained virological response was observed in 18% of cases after interferon alone and 46.9% after interferon + ribavirine. In multivariate analysis, age under 40 and combined therapy were positively correlated to sustained virological response. Premature treatment discontinuation was associated with a lack of sustained response which was unrelated to gender or liver fibrosis. Fifty seven patients received combined therapy after unsuccessful monotherapy: sustained virological response rates were 33.3% in responders-relapsers and 23.7% in non-responders to initial therapy. CONCLUSIONS: This study showed that sustained response rates were similar in non selected patients from the general population and in highly selected patients from randomised trials. These results emphasize the necessity of increasing the ratio of treated patients which is still too low in general population.

Management of hepatitis C patients: a French population-based study.

AIMS: Our aim was to assess the proportion of patients in a well-defined population reaching specialized medical care after hepatitis C diagnosis. METHODS: Hepatitis C-positive patients recorded in the population-based registry of Cote-d'Or, an administrative district in France, constituted the study population. RESULTS: Between 1994 and 1999, new hepatitis C-positive serology was diagnosed in 847 patients, of whom 690 were eligible for this study. A total of 135 patients had not been given specialized medical care after diagnosis; among them, 50.4% had a normal serum alanine transferase level at diagnosis, 62.2% had risk factors related to lifestyle (drug addiction, sexual risk...), and 26.7% were current alcoholics. The 555 other patients were involved in specialized medical care after diagnosis: 42.7% had a liver biopsy and 27.0% were treated. Treatment was carried out more often in males than in females (OR: 1.67; P<0.005), and in patients less than 65 years old (OR: 2.94; P<0.0002). Nearly 30.5% of patients with a Metavir score greater than A1F1 did not undergo treatment. CONCLUSION: This study shows that in a general population at least one patient out of five with hepatitis C infection remains outside the health care system. It also reveals that management practices vary with gender. Further surveys are needed to better understand this phenomenon.

Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene.

Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A>G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA.

Epidemiology and management of liver metastases from colorectal cancer.

OBJECTIVE/BACKGROUND: Little is known about the epidemiology and the management of liver metastases from colorectal cancer at a population level. The aim of this population-based study was to report on the incidence, treatment, and prognosis of synchronous and metachronous liver metastases. METHODS: Data were obtained from the population-based cancer registry of Burgundy (France). RESULTS: The proportion of patients with synchronous liver metastases was 14.5%. Age-standardized incidence rates were 7.6 per 100,000 in males, 3.7 per 100,000 in females. The 5-year cumulative metachronous liver metastasis rate was 14.5%. It was 3.7% for TNM stage I tumors, 13.3% for stage II, and 30.4% for stage III (P < 0.001). The risk of liver metastasis was also associated to gross features. Resection for cure was performed in 6.3% of synchronous liver metastases and 16.9% of metachronous liver metastases. Age, presence of another site of recurrence, and period of diagnosis were independent factors associated with the performance of a resection for cure. The 1- and 5-year survival rates were 34.8% and 3.3% for synchronous liver metastases. Their corresponding rates were, respectively, 37.6% and 6.1% for metachronous liver metastases. CONCLUSION: Liver metastases from colorectal cancer remain a substantial problem. More effective treatments and mass screening represent promising approaches to decrease this problem.