New, more effective and better-tolerated therapies for hepatitis C (HCV) have made the elimination of HCV a feasible objective. However, for this to be achieved, it is necessary to have a detailed ...understanding of HCV epidemiology in people who inject drugs (PWID). Respondent-driven sampling (RDS) can provide prevalence estimates in hidden populations such as PWID. The aims of this systematic review are to identify published studies that use RDS in PWID to measure the prevalence of HCV, and compare each study against the STROBE-RDS checklist to assess their sensitivity to the theoretical assumptions underlying RDS.
Searches were undertaken in accordance with PRISMA systematic review guidelines. Included studies were English language publications in peer-reviewed journals, which reported the use of RDS to recruit PWID to an HCV bio-behavioural survey. Data was extracted under three headings: (1) survey overview, (2) survey outcomes, and (3) reporting against selected STROBE-RDS criteria.
Thirty-one studies met the inclusion criteria. They varied in scale (range 1-15 survey sites) and the sample sizes achieved (range 81-1000 per survey site) but were consistent in describing the use of standard RDS methods including: seeds, coupons and recruitment incentives. Twenty-seven studies (87%) either calculated or reported the intention to calculate population prevalence estimates for HCV and two used RDS data to calculate the total population size of PWID. Detailed operational and analytical procedures and reporting against selected criteria from the STROBE-RDS checklist varied between studies. There were widespread indications that sampling did not meet the assumptions underlying RDS, which led to two studies being unable to report an estimated HCV population prevalence in at least one survey location.
RDS can be used to estimate a population prevalence of HCV in PWID and estimate the PWID population size. Accordingly, as a single instrument, it is a useful tool for guiding HCV elimination. However, future studies should report the operational conduct of each survey in accordance with the STROBE-RDS checklist to indicate sensitivity to the theoretical assumptions underlying the method.
PROSPERO CRD42015019245.
New antiviral drugs with high efficacy mean the hepatitis C virus (HCV) can now be eliminated. To achieve this, it is necessary to identify undiagnosed cases of HCV. However, the costs of testing ...should be considered when judging the overall cost‐effectiveness of treatment. This study describes the cost‐effectiveness of a community pharmacy testing service in a population of people at risk of HCV living on the Isle of Wight (United Kingdom). Dry blood spot testing was conducted in anyone with a known risk factor for HCV in 20 community pharmacies. The outcomes and costs were entered into a Markov model. Cost and health utilities from the model were used to calculate an incremental cost‐effectiveness ratio (ICER). In 24 months, 186 tests were conducted, 13 were positive for HCV RNA and six of these (46%) received treatment during the follow‐up period. All achieved a sustained virological response at 3 months. The overall cost of the testing and treatment intervention was £242 183, and the ICER for the service was £3689 per quality‐adjusted life year (QALY) gained. If screening had been restricted to just people with a history of injecting drug use (PWID) the ICER would have been £4865 per QALY gained. The service was effective at identifying people with HCV infection, and despite the additional cost of targeted testing, its cost‐effectiveness was below the commonly accepted thresholds. In this setting, restricting targeted testing to PWID would not improve the cost‐effectiveness.
Aims The primary objective of this study was to determine whether pharmacokinetic interactions occurred between interferon α‐2b (IFN) and ribavirin in patients with chronic hepatitis C infections. ...Additionally this study assessed the single and multiple‐dose pharmacokinetics of ribavirin and IFN, and compared the safety, tolerability and antiviral pharmacodynamics of IFN plus ribavirin compared with either drug alone.
Methods In this open label parallel group study, patients with chronic hepatitis C were randomized to receive IFN 3 million IU thrice weekly s.c. alone, ribavirin 600 mg twice daily p.o. alone or both drugs in combination over 6 weeks. Single and multiple dose pharmacokinetics and indices of antiviral pharmacodynamics were assessed during weeks 1 and 6, along with safety assessments during the study.
Results The range of mean ribavirin terminal phase half‐lives after single doses was 44–49 h. Comparison of week 1 and week 6 AUC(0,12h) values showed accumulation in plasma of approximately 6‐fold. The range of mean washout half‐lives after week 6 was 274–298 h, reflecting release of ribavirin from deep compartment stores. The range of single and multiple dose IFN terminal phase half‐lives was 5–7 h. IFN demonstrated an increase in bioavailability (∼2‐fold) upon multiple dose administration. Ribavirin and IFN pharmacokinetic parameters for combined ribavirin and IFN were similar to those during monotherapy with either compound, although the power of this study to detect differences was low. Serum HCV‐RNA titers and ALT concentrations were reduced by IFN alone, ribavirin alone reduced ALT concentrations only, and combined IFN plus ribavirin produced numerically greater falls in both measurements than either treatment alone. Serum concentrations of neopterin and activity of 2′,5′‐oligoadenylate synthetase (2′5′‐OAS) were increased by IFN alone and in combination with ribavirin, whereas serum 2′5′‐OAS activity was decreased and neopterin concentrations unaltered by ribavirin monotherapy. IFN and ribavirin monotherapy produced characteristic changes in safety laboratory tests (IFN—reductions in white cells, neutrophils and platelets; ribavirin—reduced haemoglobin) and characteristic adverse event profiles (IFN—headache, flu‐like symptoms, fatigue, anorexia, nausea, myalgia, and insomnia; ribavirin—headache, fatigue, myalgia, and pruritus). There was no additive effect of combination therapy on safety laboratory tests or reported adverse events. All changes were fully reversible upon treatment cessation.
Conclusions There was no evidence of pharmacokinetic interactions between IFN and ribavirin in this study. There were numerical trends indicating that the combination of IFN and ribavirin reduced titers of HCV‐RNA to a greater extent than did either treatment alone, and the safety profile of combination therapy was similar to those of both monotherapy treatments.
•Drug injecting networks resemble other naturally occurring human networks.•Hepatitis c (HCV) is clustered within drug injecting networks.•HCV transmission is prevented by treatment of nodes with ...large networks.•The risks of HCV primary infection outweight risks of reinfection.
To describe an injecting network of PWID living in an isolated community on the Isle of Wight (UK) and the results of a agent-based simulation, testing the effect of Hepatitis C (HCV) treatment on transmission.
People who inject drugs (PWID) were identified via respondent driven sampling and recruited to a network and bio-behavioural survey. The injecting network they described formed the baseline population and potential transmission pathways in an agent-based simulation of HCV transmission and the effects of treatment over 12 months.
On average each PWID had 2.6 injecting partners (range 0–14) and 137 were connected into a single component. HCV in the network was associated with a higher proportion of positive injecting partners (p = 0.003) and increasing age (p = 0.011). The treatment of well-connected PWID led to significantly fewer new infections of HCV than treating at random (10 vs. 7, p<0.001). In all scenarios less than one individual was re-infected.
In our model the preferential treatment of well-connected PWID maximised treatment as prevention. In the real-world setting, targeting treatment to actively injecting PWID, with multiple injecting partners may therefore represent the most efficient elimination strategy for HCV.
This open, multicenter study was conducted to evaluate the efficacy and safety of lamivudine prophylaxis given to chronic hepatitis B virus-(HBV) infected patients before and after orthotopic liver ...transplantation (OLT). We now present long-term data that follow our previous short-term report.
Twenty-three patients were treated with lamivudine (100 mg orally, daily); 13 (57%), were serum HBV DNA positive (Abbott Genostics, Abbott Laboratories, Chicago, IL) at study entry. Patients received lamivudine for at least 4 weeks before OLT, and for up to 50 months (median 25 months) after OLT.
Of the 23 treated patients, 17 survived to undergo OLT. Eleven patients (65%) survived up to 4 years (median 36 months) after OLT. One of the survivors stopped lamivudine because of a possible adverse reaction 9 months post-OLT, and prophylaxis with HBV immune globulin was then established. Ten survivors continue lamivudine. Eight long-term survivors have normal liver function without evidence of HBV reinfection. Of the 17 transplanted patients, 6 died. Four patients died (3 days to 5 months post-OLT) without evidence of graft reinfection. Two further patients died at 19 and 23 months post-OLT from graft failure. Both patients had YMDD variant detected at 12 months post-OLT. Two other patients with YMDD-variant HBV remain alive on lamivudine, 9 and 15 months after development of the variant.
Lamivudine, given before and after OLT, prevents significant graft reinfection for the majority of treated patients. The study has also shown that lamivudine is extremely well tolerated by liver failure patients and for a prolonged period after transplantation.
Ferroportin disease is an autosomal dominant form of hemochromatosis associated with siderosis in cells of the mononuclear phagocyte system and, to varying degrees, in hepatocytes. Ferroportin was ...investigated as a candidate gene in two pedigrees with hyperferritinaemia and siderosis in mononuclear phagocytes. The entire ferroportin coding region was sequenced and hepatic iron concentration, histology and response to treatment were determined. The results were compared with previously reported cases. The A77D mutation was detected in patient 1, his father (patient 2) and his brother (patient 3), who had portal fibrosis. The V162del mutation was detected in patient 4, who developed anemia after the third weekly venesection. While the disease is rare, A77D and V162del are the most common ferroportin mutations in Caucasians. The spectrum of clinical expression of these two mutations was reviewed in all cases described to date. These mutations were associated with fibrosis in about a third of cases. For A77D and V162del, this analysis confirms that the threshold hepatic iron concentration for development of fibrosis may be higher than for classical hemochromatosis. These two mutations, which both decreased iron export in cell culture studies, give rise to similar patterns of clinical expression and morbidity, although the highest hepatic iron concentrations have been observed with A77D. It is important for clinicians to consider ferroportin disease in cases where there are features of iron overload unrelated to
HFE, autosomal dominant inheritance and/or iron deposition in mononuclear phagocytes.
The prognosis with large hepatocellular carcinomas is poor, and only palliative treatment is available. Small tumors are amenable to several modes of treatment, including liver transplantation, ...resection, or alcohol injection, with acceptable 5-year survival rates. Although the value of screening for hepatocellular carcinoma has yet to be shown, these data, coupled with the recognition of at-risk groups and useful diagnostic techniques, might encourage the clinician to screen at-risk patients in the clinic. New imaging techniques such as ultrasonographic angiography enhanced with CO2 microbubbles, or color Doppler ultrasound, may clarify the intratumoral blood flow of small tumors.
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