Hepatitis C: Standard of Treatment and What to Do for Global Elimination

: Hepatitis C virus infection has a substantial effect on morbidity and mortality worldwide because it is a cause of cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death. Direct acting antiviral drugs available today have high efficacy and excellent safety and can be used in all patients with clinically evident chronic liver disease and in groups that demonstrate risk behaviors to reduce the spread of infection. The Global Health Strategy of WHO to eliminate hepatitis infection by 2030 assumes "a 90% reduction in new cases of chronic hepatitis C, a 65% reduction in hepatitis C deaths, and treatment of 80% of eligible people with HCV infections". In this review effective models and strategies for achieving the global elimination of HCV infection are analyzed. The screening strategies must be simple and equally effective in high-risk groups and in the general population; fast and effective models for appropriate diagnosis of liver disease are needed; strategies for direct acting antiviral drug selection must be cost-effective; linkage to care models in populations at risk and in marginalized social classes must be specifically designed and applied; strategies for obtaining an effective vaccine against HCV infection have yet to be developed

European survey on knowledge and attitudes of public health professionals on public health genomics: pilot study

Background: During the past decade a debate has arisen on the possible utility of genomic science for public health purposes. Within this context, a survey is being conducted to assess attitudes of European public health (PH) professionals belonging to European Public Health Association (EUPHA) network regarding their role in the implementation of public health genomics (PHG), and their knowledge and attitudes regarding genetic testing and the delivery of genetic services. Methods: A pilot on-line survey was conducted on professionals from Sapienza University of Rome and the Vrije University of Amsterdam. The survey tool is composed of 5 sections: Personal details, Professional activity, Knowledge on genetic testing and delivery of genetic services, Attitudes on genetic testing and delivery of genetic services, Attitudes on the role of PH professionals in PHG. Results: 34 people responded to the questionnaire, mostly medical doctors (61.8%). No respondents correctly identified all evidence-based applications of genetic testing. More than one third of respondents agreed that it would be more important to invest resources in the social and environmental causes of ill health than in genetic testing. Nearly 70% thought that PHG needs to be grounded on evidence of effectiveness, a lower rate agreed ii should be grounded on cost-effectiveness. The rate of agreement with the proposed roles of PH professionals in PHG was very high. Conclusion: This pilot study showed a positive attitude but the need to improve knowledge of PH professionals on PHG. It provided useful input for the implementation of the survey to all members of the EUPHA network

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

Due to error-prone RNA polymerase and the lack of proofreading mechanisms, to the spread worldwide and probable long-term presence in human population, HCV showed a high degree of inter- and intra-subtype genetic variability. Protease inhibitors (PIs), a new class of drugs, have been designed specifically on the HCV genotype 1 NS3 protease three-dimensional structure. The viral genetic barrier limits the efficacy of PIs, and fourteen loci in the HCV NS3 gene are involved in resistance to PIs. A sensitive method (15UI/ml) for study the HCV genetic profile of 125 strains from patients naïve to PIs, was developed through the use of new degenerate primers for subtype 1b. We observed the presence of naturally resistance-associated variants in 14% of the HCV strains (V36L, F43S, T54S, I153V, R155Q, D168A/G). T54S was the most common mutation (4%) detected. We investigated, through minimal score (m.s.) calculating, how the HCV intra-subtype 1b variability modifies the genetic barrier to PIs. For >60% of strains a single transition (m.s. of 1) was required for selection of low to medium resistance mutations, while more than one transition/transversion (m.s. ⩾2.5) or one transition plus one transversion (m.s. ⩾3.5) was necessary for most of the high level PI-resistant-associated mutations, except for A156V, for which a single transition was sufficient (m.s. of 1). However, the presence at locus 36 of the amino acid polymorphism S36 in one case and the wild type V36 in 6 isolates, encoded by unusual GTA or GTG codons, might determined a higher probability of V36L/M mutations because of the reduction of the genetic barrier. Instead, the presence of the CGA and CGT codons in the 155(th) position increases the genetic barrier for R155M or R155Q/M. The large intra-subtype variability, suggests that a routine baseline resistance test must be used before PIs-treatment

Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations

Purpose: There is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness. Methods: We performed a systematic review of full economic evaluations of health-care programs involving BRCA testing. Results: Nine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) populationbased genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i.e., testing individuals without cancer but with FH suggestive of BRCA mutation; (iii) familial mutation (FM)- based genetic screening, i.e., testing individuals without cancer but with known familial BRCA mutation; and (iv) cancer-based genetic screening, i.e., testing individuals with BRCA-related cancers. Conclusions: Currently BRCA1/2 population-based screening represents good value for the money among Ashkenazi Jews only. FHbased screening is potentially very cost-effective, although further studies that include costs of identifying high-risk women are needed. There is no evidence of cost-effectiveness for BRCA screening of all newly diagnosed cases of breast/ovarian cancers followed by cascade testing of relatives, but programs that include tools for identifying affected women at higher risk for inherited forms are promising. Cost-effectiveness is highly sensitive to the cost of BRCA1/2 testing

Greenhouse gas from moving bed based integrated fixed film activated sludge membrane bioreactors

The present paper reports the results of a nitrous oxide production investigation in a moving bed based integrated fixed film activated sludge (IFAS) membrane bioreactor (MBR) pilot plant designed in accordance with the UCT layout for biological phosphorous removal. Samples of gas and liquid were collected in order to measure the gaseous, as well as the dissolved concentration of N2O. Furthermore, the gas flow rate from each reactor was measured and the gas flux was estimated. The results confirmed that the anoxic reactor represents the main source of nitrous oxide production. A significant production of N2O was, however, also found in the anaerobic reactor, thus indicating a probable occurrence of the DPAOs activity

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C - both symptomatic and asymptomatic - have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment