Point-of-care hepatitis C testing and treatment strategy for people attending harm reduction and addiction centres for hepatitis C elimination.

According to WHO goals, the elimination of Hepatitis C Virus (HCV) by 2030 requires enhancing and simplifying HCV testing. Our aim was to create a model to assess and compare different strategies for HCV testing, linkage to care and treatment among people who access harm reduction centres (HRC) and Addiction Centres in Catalonia. A decision tree model was designed to evaluate two strategies: Hepatitis C Point-of-care (POC) "test and treat", at the community versus standard-of-care (SOC), in which HCV testing was performed at community and therapy at the hospital. Both strategies were assessed separately in HRCs (6,878 users) and Addiction Centres (13,778 users). with a time horizon of 18 months. Healthcare outcomes were HCV testing, linkage to care, treatment outcomes and reinfection rate. HCV testing was performed in 3,178 (46%) of the HRC users. Compared with SOC, POC increased access to treatment by 57% (63% vs. 6%). SVR rates were 64% in POC vs. 23% in SOC. Reinfection rates were 21% with POC compared to 24% with SOC. With POC, losses to follow-up were reduced by 41%. In the Addiction Centres, 12,566 users (91%) were screened using the two strategies. Compared to the SOC, POC increased access to treatment and linkage to care by 19% along with SVR at the same rate. Reinfection rates decreased by 6%. Thus, the implementation of a POC "test and treat" strategy at HRCs and Addiction Centres has shown to be an effective public health strategy to help eliminating HCV in accordance with WHO goal.

Significant decrease in the prevalence of hepatitis C infection after the introduction of direct acting antivirals.

BACKGROUND AND AIM: Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. METHODS: This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. RESULTS: A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. CONCLUSIONS: The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

Importance of adherence to treatment with direct-acting antivirals in hepatitis C. / Importancia de la adherencia al tratamiento de la hepatitis C con antivirales de acción directa.

The introduction of direct-acting antivirals (DAA) and the implementation of the National Strategic Plan has extended the spectrum of patients suitable for treatment to include practically all affected individuals. There has been a change in patient profile. Most patients are previously untreated, with lesser awareness of the disease, and taking polymedication, and are often under treatment with opioid replacement therapy, are active drug users or have psychiatric comorbidities. This article reviews the most important factors determining the degree of treatment adherence, in particular, drug therapy complexity, the adverse effects of DAA, demographic factors (age, ethnic group, sex, educational level, marital status) and psychosocial factors (beliefs, motivation to take therapy and negative attitude to therapy), as well as the doctor-patient relationship, knowledge/awareness of the disease, and finally comorbidities and drug abuse or abuse of other substances such as alcohol. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.

A study on the TNF-alpha system in Caucasian Spanish patients with alcoholic liver disease.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is thought to be a critical driving force of inflammatory damage in alcoholic liver disease (ALD). We aimed to establish whether there is a correlation between plasma levels of the soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) and the severity of liver damage in patients with ALD. We also aimed to elucidate whether functionally active polymorphisms in the promoter region of the TNF-alpha gene modulate the development of ALD. DESIGN: We studied 614 Spaniards. Of these, 278 were alcoholics (103 without liver histologic abnormalities, 89 with non-cirrhotic liver disease and 86 with cirrhosis) and 336 were non-alcoholics (115 healthy controls, 114 with non-alcoholic non-cirrhotic liver disease and 107 with cirrhosis unrelated to alcohol). Plasma levels of sTNFR1 and sTNFR2 were determined by ELISA and results were expressed in ng/mL and subsequently converted in log(10). TNF-alpha gene promoter region polymorphisms at the positions -238, -308 and -863 were assessed by restriction fragment length polymorphisms (RFLPs) on white cell DNA. Differences in plasma sTNFR1 and sTNFR2 levels between groups were compared with the one-way and two-factor analysis of variance test, and Student's t-test. Genotype distribution and allele frequencies in the different groups were compared using the chi(2) test or Fisher's exact test. RESULTS: sTNFR1 and sTNFR2 plasma levels were significantly higher in patients with cirrhosis than in those with non-cirrhotic liver disease (p<0.001) and individuals without liver disease (p<0.001), both in the alcoholic and the non-alcoholic group. Among cirrhotics, sTNFR1 and sTNFR2 levels had a significant positive correlation with the severity of the liver disease, graded with the Child-Pugh's score (p=0.003 and p<0.001, respectively). TNF-alpha genotype distribution and allele frequencies of the three loci assessed were similar in the groups studied, hence no particular genotype or haplotype could be linked to ALD. CONCLUSIONS: The TNF-alpha system is activated in patients with cirrhosis of the liver irrespective of aetiology. TNF-alpha polymorphisms at positions -238, -308 and -863 are not linked to ALD.

Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.

BACKGROUND: The relationship of polymorphisms of the genes that encode for alcohol-metabolizing enzymes and individual vulnerability to alcoholism and alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish women. METHODS: We performed a cross-sectional case-control study. The study group was made of 220 women. Of these, 85 were alcoholic (27 without liver disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42 healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of alcohol-metabolizing enzymes was performed using PCR-RFLP methods. RESULTS: The distribution of the allelic variants (alleles 1 and 2) in the whole subjects analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and 85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage of genotypes containing the ADH1B*2 mutant allele significantly protected against alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94; p=0.02] but was associated with an increased risk for alcoholic liver disease among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of the remaining loci showed no significant associations. CONCLUSIONS: In Caucasian Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and for alcoholic liver disease. Given the small number of alcoholic women analyzed here, these data need further validation in larger cohorts.

Polymorphisms in the interleukin-10 gene promoter and the risk of alcoholism and alcoholic liver disease in Caucasian Spaniard men.

Controversy surrounds the possible influence of the single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) gene promoter on the risk for alcoholic liver disease. Our aim was to determine whether the SNP of the IL-10 gene promoter are associated with an increased risk for alcoholism and for alcoholic liver disease in male Spaniards. The -627 C>A SNP of the IL-10 gene promoter was assessed in a cohort of 344 Caucasian Spanish men, 168 alcoholics, and 176 nonalcoholics. The alcoholic group comprised 79 individuals without liver histopathologic abnormalities and 89 patients with chronic alcoholic liver disease. The nonalcoholic group was made of 62 healthy controls and 114 patients with chronic nonalcoholic liver disease. Genotyping was performed using PCR and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by using the chi(2) test. Overall, no differences in either genotype and allele distribution was observed when comparing the four patient categories defined (P=0.62 and P=0.33, respectively). Subset analyses showed no differences in the genotype and allele distributions between all alcoholic and all nonalcoholic subjects (P=0.55 and P=0.29, respectively). This study failed to detect significant associations of the IL-10 -627C>A SNP and alcoholism or alcoholic liver disease in a cohort of Caucasian male Spaniards.