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Caroline Wheeler has been reporting on the contaminated blood scandal - the worst treatment disaster in the history of the NHS - for over two decades. She has been integral to the campaign for justice for the victims and their families, and played a pivotal role in persuading Prime Minister Theresa May to agree to the infected blood inquiry in 2019.'Death in the Blood' is based on thousands of government documents, court and inquiry transcripts, plus interviews with prime ministers, cabinet ministers, Downing Street advisers, senior civil servants, doctors, and above all the victims and their families whose personal testimony forms the beating heart of this book.

In this trial, the safety and efficacy of a recombinant chimpanzee adenovirus 3 vector priming vaccination and a recombinant modified vaccinia Ankara boost was assessed in adults who were at risk for HCV infection because of injection drug use. The vaccine did not cause serious adverse events and did elicit HCV-specific T-cell responses, but it did not prevent chronic HCV infection.

The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8–16·1) new infections and 1·5 million (1·4–1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78–82) reduction in incidence and a 61% (60–62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic. Wellcome Trust.

In two phase 3 trials involving patients with hepatitis C virus infection, including those with cirrhosis, 12 weeks of sofosbuvir–velpatasvir resulted in a sustained virologic response in 99% of patients with genotype 2 and 95% of those with genotype 3. Hepatitis C virus (HCV) genotypes 2 and 3 account for an estimated 35% of global HCV infections, affecting up to 58 million persons. 1 , 2 Unlike HCV genotype 1, genotypes 2 and 3 are common in low-income regions in Asia, sub-Saharan Africa, Latin America, and Eastern Europe. 1 Before the advent of direct-acting antiviral agents, HCV genotypes 2 and 3 were grouped together in treatment guidelines as “easy-to-treat” genotypes. However, recent studies have shown that HCV genotype 3 is associated with more rapid disease progression and lower rates of response to treatment than is HCV genotype 2, especially in patients with cirrhosis . . .

In this phase 3 study involving patients with HCV genotype 1, 2, 3, 4, or 6 and decompensated cirrhosis, sofosbuvir–velpatasvir with or without ribavirin for 12 weeks or sofosbuvir–velpatasvir for 24 weeks resulted in high rates of sustained virologic response. The number of patients with decompensated cirrhosis caused by chronic infection with the hepatitis C virus (HCV) is projected to rise in the coming decade. 1 For many years, the only treatment option for such patients was liver transplantation. Recently, however, clinical trials of newly approved direct-acting antiviral agents have shown that it is possible to treat HCV infection safely and effectively in patients with decompensated cirrhosis and that successful treatment is associated with early improvement in liver function. 2 – 11 The possible long-term benefits of treatment on existing liver disease remain unknown. The only regimen that is currently approved for the . . .

Objectives Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. Methods We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. Results We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. Conclusions Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.

Treatment options are limited for patients infected by hepatitis C virus (HCV) with advanced liver disease. We assessed the safety and efficacy of ledipasvir, sofosbuvir, and ribavirin in patients with HCV genotype 1 or 4 and advanced liver disease. We did an open-label study at 34 sites in Europe, Canada, Australia, and New Zealand. Cohort A included patients with Child-Turcotte-Pugh class B (CTP-B) or CTP-C cirrhosis who had not undergone liver transplantation. Cohort B included post-transplantation patients who had either no cirrhosis; CTP-A, CTP-B, or CTP-C cirrhosis; or fibrosing cholestatic hepatitis. Patients in each group were randomly assigned (1:1) using a computer-generated randomisation sequence to receive 12 or 24 weeks of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily (combination tablet), plus ribavirin (600–1200 mg daily). The primary endpoint was the proportion of patients achieving a sustained virological response 12 weeks after treatment (SVR12). All patients who received at least one dose of study drug were included in the safety analysis and all patients who received at least one dose of study drug and did not undergo liver transplantation during treatment were included in the efficacy analyses. Estimates of SVR12 and relapse rates and their two-sided 90% CI (Clopper-Pearson method) were provided. This exploratory phase 2 study was not powered for formal comparisons among treatment groups; no statistical hypothesis testing was planned or conducted. The trial is registered with EudraCT (number 2013-002802-30) and ClinicalTrials.gov (number NCT02010255). Between Jan 14, 2014, and Aug 19, 2014, 398 patients were screened. Of 333 patients who received treatment, 296 had genotype 1 HCV and 37 had genotype 4 HCV. In cohort A, among patients with genotype 1 HCV, SVR12 was achieved by 20 (87%, 90% CI 70–96) of 23 CTP-B patients with 12 weeks of treatment; 22 (96%, 81–100) of 23 CTP-B patients with 24 weeks of treatment; 17 (85%, 66–96) of 20 CTP-C patients (12 weeks treatment); and 18 (78%, 60–91) of 23 CTP-C patients (24 weeks treatment). In cohort B, among patients with genotype 1 HCV, SVR12 was achieved by 42 (93%, 84–98) of 45 patients without cirrhosis (12 weeks treatment); 44 (100%, 93–100) of 44 patients without cirrhosis (24 weeks treatment); 30 (100%, 91–100) of 30 CTP-A patients (12 weeks treatment); 27 (96%, 84–100) of 28 CTP-A patients (24 weeks treatment); 19 (95%, 78–100) of 20 CTP-B patients (12 weeks treatment); 20 (100%, 86–100) of 20 CTP-B patients (24 weeks treatment); one (50%, 3–98) of two CTP-C patients (12 weeks treatment); and four (80%, 34–99) of five CTP-C patients (24 weeks treatment). All five patients with fibrosing cholestatic hepatitis achieved SVR12 (100%, 90% CI 55–100). Among all patients with genotype 4 HCV, SVR12 was achieved by 14 (78%, 56–92) of 18 patients (12 weeks treatment) and 16 (94%, 75–100) of 17 patients (24 weeks treatment). Seven patients (2%) discontinued ledipasvir–sofosbuvir prematurely due to adverse events. 17 patients died, mainly from complications of hepatic decompensation. Ledipasvir–sofosbuvir and ribavirin provided high rates of SVR12 for patients with advanced liver disease, including those with decompensated cirrhosis before or after liver transplantation. Gilead Sciences.

Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0–F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3–F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790. 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81–96] in cohort 1 and n=82 [94%, 87–98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3–4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12. Combined simeprevir and sofosbuvir was efficacious and well tolerated. Janssen.

Although a few studies have been done on transmissible blood-borne viral infections in high-risk groups, little attention has been given to assessing the infection status of the general population in Afghanistan. To investigate the epidemiological status in the general population, we tested the serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), human immunodeficiency virus 1 (HIV-1) and human T-cell leukemia virus (HTLV) infections. In total, 492 samples were selected randomly from Nangarhar, Herat, Mazar-e Sharif, Kandahar, and Kabul from subjects between 25 and 70 years old. The samples were tested for the presence of HBsAg, anti-HBs, anti-HBc, anti-HDV, anti-HCV, anti-HIV-1 and anti-HTLV I/II antibodies using chemiluminescent immunoassays on Abbott Architect automated platforms. In addition, 220 HBsAg-positive samples identified among 5897 samples from the general population of the same regions of Afghanistan were included in the study and tested for both HBsAg and anti-HDV to investigate HDV prevalence in the country. Viral loads of HBV, HCV and HDV were determined in all seropositive samples using Ampliprep/Cobas TaqMan HBV, HCV, Test Roche (CA, USA), and an in-house method, respectively. Out of 492 samples, 31 (6.3%), 136 (27.6%) and 149 (30.3%) were found to be positive for HBsAg, anti-HBs and anti-HBc, respectively. Anti-HDV positivity was detected in five (2.1%) out of 234 HBsAg-positive samples (including 14 of the randomly selected samples that were not among the 220 previously identified as HBsAg positive). Only eight out of 492 (1.6%) subjects were positive for anti-HCV antibodies. Seven out of 489 (1.4%) were positive for anti-HIV-1 antibodies, and three out of 466 cases (0.6%) were positive for anti-HTLV I/II antibodies. These results suggest that Afghanistan is an intermediate endemic region for HBV, HDV and HCV infection. The prevalence of HIV-1 seems to be significantly higher than the global prevalence and that of the eastern Mediterranean region. In addition, the HTLV I/II screening results suggest that these viruses should be monitored in Afghanistan to confirm the trend observed in the current study.

Background. Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR. Methods. A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected \"low-risk\" patients; (2) Mono-HCV infected \"high-risk\" patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR. Results. In the 43 studies of HCV mono-infected \"low-risk\" patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71–3.35; I2 = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%–1.69%). For the 14 studies of HCV monoinfected \"high-risk\" patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07–33.46; I2 = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%–15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00–123.49; I2 – 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%–48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse. Conclusions. SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.