Comparison of Pathway Referrals for Liver Fibrosis Risk Stratification Performed in Diabetology and Nutrition Clinics

Purpose: A systematic screening for the presence of nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis is currently recommended in patients with type 2 diabetes mellitus (T2DM) and obesity. However, real-world data of such liver fibrosis risk stratification pathway from diabetology and nutrition clinics towards hepatology clinics are scarce. Therefore, we compared data from two pathways with or without transient elastography (TE) performed in diabetology and nutrition clinics.Patients and Methods: This is a retrospective study comparing the proportion of patients with intermediate/high risk of advanced fibrosis (AF) as defined by a liver stiffness measurement (LSM) ≥ 8kPa, among patients referred in hepatology from two diabetology-nutrition departments at Lyon University Hospital, France between November 1st 2018 to December 31st 2019.Results: Among the two diabetology and nutrition departments using TE or not, 27.5% (62/225) versus 44.2% (126/285) were referred to hepatology, respectively. The pathway using TE in diabetology and nutrition referred to hepatology a higher proportion of patients with intermediate/high risk of AF compared to the pathway without TE: 77.4% versus 30.9%, p< 0.001. In the pathway with TE, the odds of patients with intermediate/high risk of AF referred to hepatology was significantly higher: OR: 7.7, 95% CI: 3.6– 16.7, p< 0.001 after adjustment for age, sex and presence of obesity and T2D compared to the pathway without TE in diabetology and nutrition clinics. However, among the patients not referred, 29.4% had an intermediate/high risk of AF.Conclusion: A pathway-referral using TE performed in diabetology and nutrition clinics, significantly improves the liver fibrosis risk stratification and avoids over-referral. However, collaboration between diabetologist, nutritionists and hepatologists is needed to avoid under-referral

Economic Study of 2-Stage Exchange in Patients With Knee or Hip Prosthetic Joint Infection Managed in a Referral Center in France: Time to Use Innovative(s) Intervention(s) at the Time of Reimplantation to Reduce the Risk of Superinfection

Objective: Chronic prosthetic joint infections (PJI) are serious complications in arthroplasty leading to prosthesis exchange and potential significant costs for health systems, especially if a subsequent new infection occurs. This study assessed the cost of chronic PJI managed with 2-stage exchange at the Lyon University Hospital, CRIOAc Lyon reference center, France. A threshold analysis was then undertaken to determine the reimbursement tariff of a hypothetical preventive device usable at the time of reimplantation, which possibly enables health insurance to save money according to the risk reduction of subsequent new infection. This analysis was also performed for a potential innovative device already available on the market, a dual antibiotic loaded bone cement used to fix cemented prosthesis that releases high concentrations of gentamicin and vancomycin locally (G+V cement).Method: Patients >18 years, admitted for a hip or knee chronic PJI managed with 2-stage exchange, between January 1, 2013, and December 31, 2015, were retrospectively identified. Following, resource consumption in relation to inpatient hospital stay, hospitalization at home, rehabilitation care, outpatient antibiotic treatments, imaging, laboratory analysis, and consultations were identified and collected from patient records and taken into account in the evaluation. Costs were assessed from the French health insurance perspective over the 2 years following prosthesis reimplantation.Results: The study included 116 patients (median age 67 y; 47% hip prosthesis). Mean cost of chronic PJI was estimated over the 2 years following prosthesis reimplantation at €21,324 for all patients, and at €51,697 and €15,745 for patients with (n = 18) and without (n = 98) a subsequent new infection after reimplantation, respectively. According to the threshold analysis the reimbursement tariff (i) should not exceed €2,820 for a device which can reduce the risk of a new infection by 50% and (ii) was between €2,988 and €3,984 if the G + V cement can reduce the risk of a new infection by 80% (this reduction risk is speculative and has to be confirmed by clinical trials).Conclusion: This study revealed that chronic PJI requiring a 2-stage revision is costly, with significant costs in relation to the reimplantation procedure (about 15 k€). However, following reimplantation the rate of subsequent new infection remained high, and the cost of reimplantation following a new infection is considerable, reaching 50k€ per patient. These first cost estimates of managing chronic PJI with 2-stage exchange in France underline the economic interest of preventing new infections

Longitudinal liver stiffness assessment in patient with chronic hepatitis C undergoing antiviral therapy.

BACKGROUND/AIMS:Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage

A poxvirus vaccine is safe, induces T-cell responses, and decreases viral load in patients with chronic hepatitis C.

International audienceBACKGROUND & AIMS: Therapy for chronic hepatitis C (CHC) has limited efficacy, adverse effects, and high costs. Cohort and vaccine-based preclinical studies have indicated the importance of T-cell-based immunity in controlling viral infection. TG4040 is a recombinant poxvirus vaccine that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B. We performed a phase I clinical trial to assess the safety, immunogenicity, and early antiviral efficacy of TG4040 in patients with CHC. METHODS: In an open-label, dose-escalating study, patients with mild CHC (genotype 1) were assigned to 3 groups of 3 patients each; they received subcutaneous injections of 10⁶, 10⁷, or 10⁸ plaque-forming units of TG4040 on study days 1, 8, and 15. Six additional patients were given the highest dose of vaccine (10⁸ plaque-forming units). Patients were followed for 6 months after the last injection. T-cell-based and antibody responses and levels of HCV RNA were measured. RESULTS: All 3 doses of TG4040 were well tolerated, without serious adverse events. Vaccine-induced HCV-specific cellular immune responses were observed in 5 of the 15 patients (33%). A transient decrease in circulating levels of HCV RNA, from -0.52 log₁₀ to -1.24 log₁₀, was observed in 8 patients; in 5 patients, the lowest level of HCV RNA was observed on day 37, after the first injection. The most pronounced decrease in viral load occurred in 2 patients, who also had marked vaccine-induced T-cell responses. CONCLUSIONS: In patients with CHC, the viral-vector-based vaccine TG4040 had a good safety profile, induced HCV-specific cellular immune responses, and reduced viral load. This vaccine should be investigated in further clinical studies, in combination with standard of care

Liver stiffness evolution in treated <i>vs</i> untreated patients: Significant changes over time in treated <i>vs</i> untreated patients.

<p>Liver stiffness evolution in treated <i>vs</i> untreated patients: Significant changes over time in treated <i>vs</i> untreated patients.</p

Mean percentage of change in liver stiffness from baseline to end of study according to treatment and virologic response.

<p>Mean percentage of change in liver stiffness from baseline to end of study according to treatment and virologic response.</p

Factors associated with liver stiffness improvement.

<p>BMI, body mass index; FU, follow-up.</p

Liver stiffness evolution in patients with measurements above the cut-off value for advanced fibrosis and cirrhosis according to virologic response.

<p>The y axis is in logarithmic scale. The black dots indicate the mean liver stiffness value at each time points.</p

Liver stiffness variations during study and after follow-up and according to virologic response.

<p>Results are expressed as the mean.</p>*<p><i>P</i> 0.006 SVR vs RR and NR.</p>♦<p><i>P</i><0.0001.</p>◊<p>for untreated or treated patients, respectively.</p