Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Sustained viral response (SVR) is the optimal outcome of hepatitis C virus (HCV) therapy, yet more detailed data are required to confirm its clinical value. Individuals receiving treatment in 1996‐2011 were identified using the Scottish HCV clinical database. We sourced data on 10 clinical events: liver, nonliver, and all‐cause mortality; first hospitalisation for severe liver morbidity (SLM); cardiovascular disease (CVD); respiratory disorders; neoplasms; alcohol‐intoxication; drug intoxication; and violence‐related injury (note: the latter three events were selected a priori to gauge ongoing chaotic lifestyle behaviours). We determined the association between SVR attainment and each outcome event, in terms of the relative hazard reduction and absolute risk reduction (ARR). We tested for an interaction between SVR and liver disease severity (mild vs. nonmild), defining mild disease as an aspartate aminotransferase‐to‐platelet ratio index (APRI) <0.7. Our cohort comprised 3,385 patients (mean age: 41.6 years), followed‐up for a median 5.3 years (interquartile range: 3.3‐8.2). SVR was associated with a reduced risk of liver mortality (adjusted hazard ratio [AHR]: 0.24; P < 0.001), nonliver mortality (AHR, 0.68; P = 0.026), all‐cause mortality (AHR, 0.49; P < 0.001), SLM (AHR, 0.21; P < 0.001), CVD (AHR, 0.70; P = 0.001), alcohol intoxication (AHR, 0.52; P = 0.003), and violence‐related injury (AHR, 0.51; P = 0.002). After 7.5 years, SVR was associated with significant ARRs for liver mortality, all‐cause mortality, SLM, and CVD (each 3.0%‐4.7%). However, we detected a strong interaction, in that ARRs were considerably higher for individuals with nonmild disease than for individuals with mild disease. Conclusions: The conclusions are 3‐fold: (1) Overall, SVR is associated with reduced hazard for a range of hepatic and nonhepatic events; (2) an association between SVR and behavioral events is consistent with SVR patients leading healthier lives; and (3) the short‐term value of SVR is greatest for those with nonmild disease. (Hepatology 2015;62:355–364

We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer.

Background and AimsPeople who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person‐years), but a 2.3‐fold elevated transmission risk among recently released (< 6 months) PWID. We evaluated the contribution of incarceration to HCV transmission among PWID and the impact of prison‐related prevention interventions, including scaling‐up direct‐acting antivirals (DAAs) in prison.DesignDynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration.SettingScotland, UK.ParticipantsA simulated population of PWID.MeasurementsPopulation‐attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling‐up DAAs in prison and/or preventing the elevated risk associated with prison release.FindingsIncarceration contributes 27.7% [PAF; 95% credible interval (CrI) –3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4–13.3%) and 9.7% (95% CrI = 7.7–12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = –28.5 to 18.0%) and 4.7% (95% CrI = –11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7–57.5%) and 33.3% (95% CrI = 15.6–43.6%) or scaling‐up prison HCV treatments to 80% of chronic PWID prison entrants with sufficient sentences (>16 weeks) could reduce incidence and prevalence by 45.6% (95% CrI = 38.0–51.3%) and 45.5% (95% CrI = 39.3–51.0%), respectively.ConclusionsIncarceration and the elevated transmission risk following prison release can contribute significantly to hepatitis C virus transmission among people who inject drugs. Scaling‐up hepatitis C virus treatment in prison can provide important prevention benefits.

Summary Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison- and community-based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment-naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%–66%) and 63% (95% CI 60%–66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%–81%), 59% (95% CI 42%– 75%) and 45% (95% CI 29%–62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment achieves similar outcomes to community-based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.