P53 The cost-effectiveness of HCV antiviral treatment for injecting drug user populations

Abstract

pathogenesis of HCV-related HCC in relation to tumour progression and angiogenesis. Method 30 patients with HCV-related cirrhosis (15 patients with histologically-proven HCC and 15 patients without HCC) and 15 healthy subjects were enrolled in the study. The severity of liver disease was assessed according to Child-Pugh classification and the Model for End Stage Liver Disease (MELD) score. The tumour stage was classified using the Cancer of the Liver Italian Program (CLIP) scoring system. Histological tumour grading was performed according to the Edmondson and Steiner's criteria and the surrounding liver tissue was examined for assessing the modified histological activity index (HAI), presence of cirrhosis and the grade of steatosis. Expressions of MIP-1a/CCL3, CD68 [a marker for tumour-associated macrophages (TAM)] and CD105 (Endoglin) [for tumour angiogenesis and determination of microvessel density (MVD)] were studied in HCC and adjacent non-neoplastic liver tissues by immunohistochemistry. Serum MIP-1a/CCL3 levels were measured using solid phase sandwich enzyme linked immunosorbant assay kit. The sensitivity and specificity of serum levels of MIP-1a/CCL3 as markers for diagnosis of HCC have been assessed by plotting a receiver-operating characteristic (ROC) curve. Results Patients with HCV-related HCCs showed significant increases in MIP-1a/CCL3 expression, CD68+ TAM count and CD105 + MVD in tumour tissues compared with adjacent non-neoplastic liver tissues (p¼0.0004, p<0.001 and p<0.001 respectively). Serum MIP-1a/CCL3 levels were significantly higher in patients with and without HCC than in healthy subjects and in HCC patients than in patients without HCC (p<0.001). By plotting a ROC curve, the sensitivity and specificity of serum MIP-1a/CCL3 in discriminating cirrhotic patients with and without HCC were found to be 100% and 93.3% respectively at a cut-off value of 17.5 pg/ml. The MIP-1a/CCL3 expression in HCC tissues showed positive correlations with serum MIP-1a/CCL3 levels; tumour size, stage, histopathological grade; serum a-fetoprotein levels and CD68+ TAM count and CD105 + MVD in HCCs (p<0.05). Also, CD68+ TAM count and CD105 + MVD in HCC tissues were positively correlated (p<0.001). On the other hand, no correlations were found between MIP-1a/CCL3 expression, CD68+ TAM count and CD105 + MVD in HCCs on one hand and serum levels of aminotransferases, Child-Pugh score, MELD score and HAI and steatosis grade in the surrounding liver tissue (p>0.05). Conclusion The CC chemokine, MIP-1a/CCL3, may play an important role in the pathogenesis and progression of HCC in HCVrelated liver disease, possibly, through migration of macrophages to tumour microenvironment and enhancement of angiogenesis. MIP1a/CCL3 may also serve as a potential serum biological marker and a useful therapeutic target for HCC.

Cost-effectiveness of HCV case-finding for people who inject drugs via dried blood spot testing in specialist addiction services and prisons

“…An existing dynamic, deterministic model of HCV transmission, progression and HCV treatment was adapted to project the impact of introducing DBS testing in prisons and addiction services 11. See online supplementary appendix for details and model schematics.…”

“…Costs were inflated to 2011 GBP using the Health and Community Hospital Service pay and prices index 21. Additional PWID treatment delivery costs were applied 11. We assumed that undiagnosed individuals would not incur HCV-related healthcare costs unless progressing to decompensated disease 9…”

“…Unlike previous economic evaluations of HCV testing in these settings,9 10 we incorporate a dynamic mathematical model to capture the potential prevention benefits of treatment, which can substantially increase the cost-effectiveness of HCV treatment for PWID 11. A dynamic model accounts for the individual and population benefits of treatment, as well as the dynamic nature of incarceration, especially among PWID.…”

How cost‐effective is hepatitis C virus treatment for people who inject drugs?

“…[8][9][10][11][12][13][14][15][16] This is crucially important as few injectors are treated for HCV, 2,17 and some clinicians discourage treatment of current PWID due to perceived risks of reinfection or non-completion/noncompliance. This is despite the available evidence indicting that reinfection rates following treatment are low 18,19 and sustained viral response (SVR) rates are similar among PWID as compared to noninjectors.…”

“…3 Indeed, treating PWID may be more cost-effective than treating former or non-injectors because of the substantial benefits achieved through averting secondary infections, despite the risk of reinfection or lower SVR rates among PWID. 8 The result of omitting these transmission dynamics is that Visconti et al's model might give a misleading picture. Based on their model, non-injectors and ex-injectors would be preferentially treated rather than PWID-whereas the reverse may have been found if the model had been dynamic and allowed for any potential prevention benefit.…”