Screening for alcohol use in primary care: assessing French general practitioner practices.

Alcohol use is a leading risk factor for premature death and disability. To tackle this issue, more systematic and accurate screening for at-risk consumption is needed in healthcare systems, especially by general practitioners (GPs). We assessed the frequency of at-risk consumption screening by GPs in France. We also identified characteristics associated with more frequent screening and greater use of validated screening tools by these healthcare providers. A cross-sectional survey was conducted among a representative sample of French GPs. Multinomial logistic regressions were used to identify factors associated with more frequent screening and greater use of validated screening tools. Response rate was of 73%. Of the 2412 participants, 42.8% screened all their patients systematically and repeatedly, while 48.0% never used standardized tools to screen potentially at-risk patients. Among other characteristics, being aware of and using the "early identification and brief intervention" screening strategy, and feeling absolutely comfortable talking with patients about reducing or stopping their alcohol use, were both associated with more frequent screening and use of standardized tools. Our results on at-risk alcohol use screening highlight an improvement over data from previous studies. Nevertheless, better training of French GPs in good alcohol screening practices-specifically, increased screening frequency and greater use of standardized tools-may improve identification of at-risk patients.

Impaired health-related quality of life in the HCV cure era: who is concerned? (ANRS CO22 HEPATHER French cohort).

PURPOSE: Hepatitis C virus (HCV) cure after treatment with direct-acting antivirals (DAAs) can improve health-related quality of life (HRQoL). However, specific groups with chronic HCV may still exhibit worse post-cure HRQoL because of persisting severe liver fibrosis or social vulnerability factors (e.g. unhealthy alcohol use, living in poverty). We assessed the effect of such factors on longitudinal measures of HRQoL in chronic HCV patients. METHODS: ANRS CO22 HEPATHER is a prospective cohort of chronic HCV patients receiving DAAs, which included notably patients with social vulnerability factors, a population usually under-represented in clinical trials. Multivariable mixed-effects linear regression models helped identify factors associated with longitudinal measures of HRQoL (PROQOL-HCV scores). RESULTS: At enrolment, 52.4% of the 2740 participants were men, median age was 56 years [interquartile range 50-64], and 21.5% had severe liver fibrosis (FIB-4 > 3.25). Twenty-eight per cent reported current or past unhealthy alcohol use [> 2(3) alcohol units per day for women (men)], and 28.1% were living in poverty (standard of living under 1015€/month per household consumption unit). At first PROQOL-HCV completion, 54.0% of patients were HCV-cured. After multivariable adjustment, people with current or past unhealthy alcohol use, individuals living in poverty, those with severe liver fibrosis, and women had worse HRQoL in the dimensions explored. Conversely, HCV cure was associated with better HRQoL. CONCLUSIONS: Specific socially vulnerable groups of patients with chronic HCV infection still experience impaired HRQoL, independently of HCV cure. Patient-centred interventions, including social support and referral for comorbidities, should be prioritized for them. Trial registration with ClinicalTrials.gov NCT01953458.

Patient-reported outcomes with direct-acting antiviral treatment for hepatitis C in West and Central Africa (TAC ANRS 12311 trial).

Background & Aims: Patient-reported outcomes (PROs) are poorly documented for patients with chronic hepatitis C on direct-acting antiviral (DAA) treatment in low-to-middle-income countries. We documented PROs during and after DAA treatment in participants of the TAC ANRS 12311 trial (West and Central Africa). Methods: Trial participants received a 12-week regimen containing either sofosbuvir plus ribavirin (HCV genotype 2, n = 40), or sofosbuvir plus ledipasvir (HCV genotypes 1 and 4, n = 80). Health-related quality of life (SF-12), fatigue (Piper Fatigue scale), and self-reported symptoms (35-symptom list) were assessed at enrolment (Week (W) 0), during treatment (W2, W4, W8 and W12) and after treatment (W24 and W36). These PROs were compared between W0 and W36 (Wilcoxon signed-rank or McNemar tests). Mixed-effects linear regression models helped identify correlates of physical and mental quality of life component summaries (PCS and MCS) in a longitudinal analysis. Results: Most PROs were significantly improved 24 weeks after treatment end (W36), without significant differences between treatment groups. For the post-treatment period, multivariable analysis showed significant increases in PCS for patients with cirrhosis and in MCS for patients in the sofosbuvir plus ribavirin group. A higher number of self-reported symptoms at W0 was associated with lower PCS and MCS, older age and cirrhosis with lower PCS, and male sex and HCV cure with higher PCS. Conclusions: Sofosbuvir-based DAA therapy was associated with a significant improvement in PROs 6 months after treatment end in patients with chronic HCV infection from Central and West Africa. These findings may guide HCV treatment providers in low-to-middle-income countries to deliver pre-treatment information concerning the benefits of DAAs beyond viral eradication. ClinicalTrialsgov Identifier: NCT02405013. Impact and implications: Perceptions and experiences (i.e. "patient-reported outcomes") of patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) are poorly documented in the African setting. This study shows significant improvements in health-related quality of life, fatigue, and self-reported symptoms 24 weeks after the end of a 12-week sofosbuvir-based DAA regimen in 120 patients from Central and West Africa. These findings substantially add to the body of knowledge about DAA therapy in the African setting. Treatment providers should be encouraged to inform patients of the benefits of DAAs beyond viral eradication, to increase treatment adherence and retention in care.

Benefits of tailored hepatocellular carcinoma screening in patients with cirrhosis on cancer-specific and overall mortality: A modeling approach.

To validate cancer screening programs, experts recommend estimating effects on case fatality rates (CFRs) and cancer-specific mortality. This study evaluates hepatocellular carcinoma (HCC) screening in patients with cirrhosis for those outcomes using a modeling approach. We designed a Markov model to assess 10-year HCC-CFR, HCC-related, and overall mortality per 100,000 screened patients with compensated cirrhosis. The model evaluates different HCC surveillance intervals (none, annual [12 months], semiannual [6 months], or quarterly [3 months]) and imaging modalities (ultrasound [US] or magnetic resonance imaging [MRI]) in various annual incidences (0.2%, 0.4%, or 1.5%). Compared to no surveillance, 6-month US reduced the 10-year HCC-CFR from 77% to 46%. With annual incidences of 0.2%, 0.4%, and 1.5%, the model predicted 281, 565, and 2059 fewer HCC-related deaths, respectively, and 187, 374, and 1356 fewer total deaths per 100,000 screened patients, respectively. Combining alpha-fetoprotein screening to 6-month US led to 32, 63, and 230 fewer HCC-related deaths per 100,000 screened patients for annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 3-month US reduced cancer-related mortality by 14%, predicting 61, 123, and 446 fewer HCC-related deaths per 100,000 screened patients with annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 6-month MRI (-17%) and 12-month MRI (-6%) reduced HCC-related mortality. Compared to 6-month US, overall mortality reductions ranged from -0.1% to -1.3% when using 3-month US or MRI. A US surveillance interval of 6 months improves HCC-related and overall mortality compared to no surveillance. A shorter US interval or using MRI could reduce HCC-CFR and HCC-related mortality, with a modest effect on overall mortality.

Quality of life of patients irradiated for head and neck cancer and impact of rehabilitation with a removable dental prosthetic: 1-year follow-up study.

Background: Head and neck cancer and its treatment cause significant functional, aesthetic, and social disabilities. These disabilities have a major impact on the quality of life of patients. When irradiation is required, removable dental prostheses are often the treatment of choice. This study investigated whether removable prosthetic rehabilitation improved patient function and aesthetics over the long term. Material and Methods: In this prospective study, we assessed quality of life in 78 patients with the General Oral Health Assessment Index (GOHAI) questionnaire. Assessments were performed before, and 1 week, 3 months, 6 months, and 12 months after denture insertion. We evaluated whether quality of life was influenced by the type of removable prosthesis and the primary tumour location. Results: We constructed mixed-effects linear regression models to identify correlates of the overall GOHAI score (GOAHI-add score) and the three domain-scores (functional, psychosocial, and discomfort/pain) in a longitudinal analysis over a 12-month follow-up. We compared scores (GOHAI-add score and domain-scores) in multivariate analyses between baseline (T0) and four post-insertion timepoints to determine significant changes. Conclusions: We found that removable prosthetic rehabilitation had an influence on the evolution of quality of life. The psychosocial component scores increased steadily over the year and changed more significantly than the functional and discomfort-pain components. The mandibular location of the primary lesion had a negative influence on quality of life. The type of removable prosthesis did not influence the results. Key words:Quality of life, head and neck cancer, GOHAI, dental prosthesis, radiotherapy.

Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa.

BACKGROUND: Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d'Ivoire and Senegal. METHODS: Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country's predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo 'no DAA treatment' as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d'Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country's per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d'Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d'Ivoire and Senegal) and 0.2 (Cameroon) times the country's per-capita GDP. CONCLUSIONS: Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda.

Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes.

BACKGROUND & AIMS: Though lifestyle interventions can reverse disease progression in people with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), unawareness about disease severity might compromise behavioural changes. Data from this first international cross-sectional survey of individuals with NAFLD/NASH were used to identify correlates of both unawareness about fibrosis stage and its association with adherence to lifestyle adjustments. METHODS: Adults with NAFLD/NASH registered on the platform Carenity were invited to participate in an online 20-min, six-section survey in Canada, France, Germany, Italy, Spain and the United Kingdom to describe their experience with NAFLD/NASH and its care (N = 1411). Weighted binary and multinomial logistic regressions were performed to estimate the effect of explanatory variables on unawareness of fibrosis stage and poor adherence to lifestyle changes respectively. RESULTS: In the study group, 15.5% had obesity and 59.2% did not know their fibrosis stage. After multiple adjustments, individuals with a body mass index (BMI) ≥35 were over twice as likely to not know their fibrosis stage. People with a BMI >30 had a threefold higher risk of having poor adherence to lifestyle changes. Unawareness about fibrosis stage was also significantly associated with poor adherence to lifestyle adjustments. CONCLUSIONS: As fibrosis stage is becoming the main predictor of NAFLD progression, improving patient-provider communication-especially for people with obesity-about liver fibrosis stage, its associated risks and how to mitigate them, is needed. Training for healthcare professionals and promoting patient educational programmes to support behaviour changes should also be included in the liver health agenda.

Serum Cadmium Levels and Risk of Metabolic Syndrome: A Cross-Sectional Study.

The increase in the prevalence of metabolic disorders globally is becoming a public health concern. Previous studies have reported an association between environmental exposures to hazardous substances, including various heavy metals, and the risk for metabolic syndrome. However, reports on the contributions of cadmium (Cd) to the risk for obesity and diabetes remain inconsistent. This study aims to investigate an association between serum Cd levels (SCL) and diabesity and dyslipidemia risk scores. A total of 140 subjects were identified from a public academic institution in Lebanon. Socio-demographic information, diabesity, and obesity risk scores were determined using an interview-based adapted FINDRISC questionnaire and analysis of an acquired blood sample. SCL was quantified using inductively coupled plasma mass spectrometry (ICP-MS). The statistical analysis relied on a chi-squared test and multivariate logistic regression models, along with checks for confounders and effect modifiers. Our results showed a Cd geometric mean of 4.04 µg/L (± 2.5). High SCL was significantly associated with higher dyslipidemia risk (OR: 3.05 [95% CI: 1.19-7.86], P = 0.02), even after adjusting for confounders. However, SCL did not show a statistically significant association with diabetes and obesity outcomes. Elevated SCL increases the risk of dyslipidemia and alters the blood lipid profile. In addition, our findings do not support a role for Cd in diabesity.

Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: Results of a prospective, nationwide study.

BACKGROUND: Recent data suggest that alcohol-related hepatocellular carcinoma (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC characteristics and outcomes in an alcohol-related group (group A) and a non-alcohol-related group (group NA). METHODS: A total of 1207 patients with newly diagnosed HCC were prospectively included between May 2008 and October 2009. Patients with multiple causes (alcohol plus another cause) were excluded. Patients were followed every year for 5 years. Recorded variables, including etiologies were tested as prognostic factors of survival in a multivariate Cox model after adjustments for a lead-time bias. RESULTS: In all, 894 patients were analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol-related HCC was more likely to be diffuse and detected in patients with a worse performance status and worse liver function. After adjustments for a lead-time bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A, respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol non-abstinent groups, respectively (P = .09). The prognostic role of alcohol disappeared when survival was assessed at each Barcelona Clinic Liver Cancer (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P < .0001). CONCLUSIONS: In comparison with patients with non-alcohol-related HCC, patients with alcohol-related HCC have reduced OS, mainly because of worse liver function and tumor characteristics at diagnosis, as attested by similar survival within each BCLC stage. Cancer 2018;124:1964-72. © 2018 American Cancer Society.

Hepatocellular carcinoma screening in patients with compensated hepatitis C virus (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling approach.

UNLABELLED: Because of the ongoing debate on the benefit of ultrasound (US) screening for hepatocellular carcinoma (HCC), we assessed the impact of screening on hepatitis C virus (HCV)-related compensated cirrhosis patients aware of their HCV status. A Markov model simulated progression from HCC diagnosis to death in 700 patients with HCV-related compensated cirrhosis aware of their HCV status to estimate life expectancy (LE) and cumulative death at 5 years. Five scenarios were compared: S1, no screening; S2, screening by currently existing practices (57% access and effectiveness leading to the diagnosis of 42% at Barcelona Clinic Liver Cancer stage [BCLC-0/A]); S3, S2 with increased access (97%); S4, S2 with an efficacy of screening close to that achieved in a randomized controlled trial leading to the diagnosis of 87% of patients at stage BCLC-0/A; S5, S3+S4. The analysis was corrected for lead-time bias. Currently existing practices of HCC screening increased LE by 11 months and reduced HCC mortality at 5 years by 6% compared to no screening (P = 0.0013). Compared to current screening practices, we found that: 1) increasing the rate of access to screening would increase LE by 7 months and reduce HCC mortality at 5 years by 5% (P = 0.045); 2) optimal screening would increase LE by 14 months and reduce HCC mortality at 5 years by 9% (P = 0.0002); 3) the combination of an increased rate of access and optimal effectiveness of HCC screening would increase LE by 31 months and decrease HCC mortality at 5 years by 20% (P < 0.0001). CONCLUSION: The present study shows that US screening for HCC in patients with compensated HCV-related cirrhosis aware of their HCV status improves survival and emphasizes the crucial role of screening effectiveness.

Impact of emerging hepatitis C virus treatments on future needs for liver transplantation in France: a modelling approach.

BACKGROUND: In light of the impact of emerging hepatitis C virus treatments on morbidity and mortality, we sought to determine whether candidates for liver transplantation for hepatocellular carcinoma and decompensated cirrhosis will decrease sufficiently to match liver grafts for hepatitis C virus-infected patients. AIMS: Using a Markov model, we quantified future liver graft needs for hepatitis C virus-induced diseases and estimated the impact of current and emerging treatments. METHODS: We simulated progression of yearly-hepatitis-C-virus-infected cohorts from the beginning of the epidemic and calculated 2013-2022 candidates for liver transplantation up until 2022 without and with therapies. We compared these estimated numbers to projected trends in liver grafts for hepatitis C virus. RESULTS: Overall, current treatment would avoid transplantation of 4425 (4183-4684) potential candidates during the period 2013-2022. It would enable an 88% and 42% reduction in the gap between liver transplantation activity and candidates for hepatocellular carcinoma and decompensated cirrhosis, respectively. Emerging hepatitis C virus treatments would allow adequacy in transplant activities for hepatocellular carcinoma. However, they would not lead to adequacy in decompensated cirrhosis from 2013 to 2022. Results were robust to sensitivity analysis. CONCLUSION: Our study indicates that patients will benefit from public health policies regarding hepatitis C virus screening and therapeutic access to new emerging treatments.

Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: a meta-analysis.

BACKGROUND & AIMS: Recent studies suggested that SVR rates might be lower in HCV patients with insulin resistance (IR) than in patients without IR, but the extent of the impact of IR on treatment response has not been established. We aimed to confirm the role of IR assessed by the homoeostasis model assessment (HOMA-IR) on SVR and to determine its magnitude. METHODS: We performed meta-analysis of studies evaluating the impact of IR in HCV patients treated with pegylated interferon and ribavirin. RESULTS: Fourteen studies involving 2732 patients were included. SVR was less frequent in patients with IR than in patients without IR (mean difference: -19.6%, 95% CI: -29.9% to -9.4%, p<0.001). In sensitivity analyses according to HCV-1 patients, patients with IR also less frequently attained a SVR than patients without IR (mean difference: -13.0%, 95% CI: -22.6% to -3.4%, p=0.008). In addition, the baseline HOMA-IR index was lower in responders than in non-responders (mean difference: -0.92, 95% CI: -1.53 to -0.32, p<0.001). In sensitivity analyses restricted to HCV-1 patients, the baseline HOMA-IR index remained lower in responders than in non-responders (mean difference: -0.63, 95% CI: -1.13 to -0.14, p<0.001). CONCLUSIONS: HCV patients with IR have a 20% lower SVR than patients without IR. The baseline HOMA-IR index is a major determinant of SVR.