Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection: A nationwide cohort study

This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service‐National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person‐years of follow‐up (median follow‐up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20‐1.35), HCV infection (HR: 1.31, 95% CI: 1.16‐1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31‐1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92‐3.15)], gallbladder [1.55 (1.05‐2.29)], pancreas [1.52 (1.07‐2.15)], stomach [1.39 (1.22‐1.58)], lung [1.27 (1.04‐1.55)], colorectum [1.21 (1.03‐1.42)] and thyroid cancer [1.20 (1.05‐1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35‐79.78)], gallbladder [2.90 (1.62‐5.18)], prostate [2.51 (1.65‐3.82)] and thyroid cancer [1.46 (1.10‐1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.     

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high‐risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co‐infected. SVR among those with HCV mono‐infection was 64% by intention to treat; SVR was 68% among HCV/HIV co‐infection. Independent predictors of SVR in HCV mono‐infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85–0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13–4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03–4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31–6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype‐1 infection. Interferon‐based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision‐making.     

Prevalence,mortality and healthcare utilization among Medicare beneficiaries with Hepatitis C in Haemodialysis units

Hepatitis C (HCV) is more common among patients with end‐stage renal disease requiring haemodialysis compared to the general population. Thus, we aimed to assess trends in prevalence, health resource utilization and mortality among Medicare beneficiaries with HCV on haemodialysis. This is a retrospective study of outpatient and inpatient claims for Medicare beneficiaries receiving haemodialysis (2005‐2016). A total of 291 663 subjects on haemodialysis were included (67.3 ± 15.2 years, 55% male, 55% white, 49% age‐based eligibility). The prevalence of HCV in subjects on haemodialysis was stable and was significantly higher (mean 4.2% in 2005‐2016, P = 0.50 for the trend) than in subjects not on haemodialysis (<1%). In multivariate analysis, liver cirrhosis (odds ratio = 3.4 (95% CI = 3.3‐3.6)) was an independent predictor of 1‐year mortality among haemodialysis patients. Mean total inpatient payments in dialysis patients with HCV remained stable during 2005 ($73 803) through 2016 ($72 133) (trend P = 0.54) while mean total outpatient payment decreased from 2005 ($53 497) to 2016 ($35 439; trend P = 0.0013). In multivariate analysis, after adjustment for age, gender, race and location, both HCV and cirrhosis remained significant contributors to greater spending [HCV: inpatient +22.1% (+19.2%‐25%), HCV: outpatient +18.4% (+14.6%‐22.2%), cirrhosis: inpatient +59.7% (+56.9%‐62.6%), cirrhosis: outpatient +9.4% (+6.2%‐12.6%)]. In conclusion, HCV‐infected Medicare patients receiving haemodialysis incur greater resource utilization; mortality is higher in patients with cirrhosis only. Although HCV prevalence in Medicare haemodialysis recipients is higher than in patients without haemodialysis, these rates are lower than reported, suggesting potential under‐screening for HCV in this high‐risk population.     

Impact of hepatitis C virus infection on the risk of death of alcohol‐dependent patients

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio‐demographic and alcohol use characteristics, liver function tests for the assessment of alcohol‐related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9–50.2 years), duration of alcohol abuse was 18 years (IQR: 11–24 years), and median alcohol consumption was 200 g/day (IQR: 120–275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow‐up was 3.1 years (IQR: 1.5–5.1 years) accounting for 2,345 person‐years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05–2.80), alcohol‐related liver disease (HR = 3.55, 95%CI: 1.93–6.53) and HCV/HIV co‐infection (HR = 3.86 95%CI: 2.10–7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3–7.3; P = 0.007). Among patients with alcohol‐related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.     

Longitudinal evolution of vertically HIV/HCV–co‐infected vs HCV–mono‐infected children

HIV co‐infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV‐infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co‐infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV–co‐infected patients and age‐ and sex‐matched vertically HCV–mono‐infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty‐seven co‐infected patients were compared with 67 matched HCV–mono‐infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co‐infected vs 20% mono‐infected had progressed to advanced fibrosis (P = .617). Peg‐IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P‐value < .001). At treatment initiation, co‐infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard‐to‐treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV–co‐infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg‐IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct‐acting antivirals against HCV for vertically co‐infected patients.     

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004–2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51–9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24–9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47–60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01–40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.     

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID‐19 has not been studied. We analysed 70 COVID‐19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID‐19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID‐19 combined with HBV infection. Compared with COVID‐19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28‐69)vs 21(14‐30), P = .000; 40(25‐54) vs 23(18‐30), P = .000; 34.0(27.2‐38.7) vs 37.2(31.1‐41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co‐infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co‐infected patients group. Age and c‐reactive protein (CRP) level were independent risk factors for recovery of patients with COVID‐19 combined with HBV infection. The original characteristics of COVID‐19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID‐19.     

Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B

The short‐term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.     

The impact of viral hepatitis‐related hepatocellular carcinoma to post‐transplant outcomes

Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002–2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV–HBV co‐infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co‐infected, and 2432 had nonviral causes of liver disease. In follow‐up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV–HBV co‐infection and nonviral liver disease, respectively (P < 0.0001). Post‐transplant mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV–HBV 28.5% and nonviral 28.5% (P < 0.0001). This difference was significant starting one year post‐transplant and became even more prominent later in follow‐up. Five‐year post‐transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV–HBV and 69.1% in nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also independently associated with an increased risk of both graft failure (adjusted hazard ratio = 1.84 (1.46–2.33), P < 0.0001) and mortality (1.35 (1.21–1.50), P < 0.0001) in multivariate analysis. Patients with HCV‐related HCC are at higher risk of adverse post‐transplant outcomes. These patients should be considered for preemptive interferon‐free antiviral therapy prior to or immediately following liver transplantation.     

Hepatitis B reactivation during cancer chemotherapy: an international survey of the membership of the American Association for the Study of Liver Diseases

Hepatitis B virus reactivation (HBVr) can be a serious complication of cancer chemotherapy. However, underutilization of HBV screening and secondary underutilization of antiviral prophylaxis have been frequently reported. The authors electronically distributed a 30‐point questionnaire to members of the American Association for the Study of Liver Diseases to capture experiences with HBVr during cancer chemotherapy. The questionnaire specified diagnostic criteria and collected information on HBV screening, antiviral prophylaxis and clinical outcomes. Ninety‐nine respondents reported 188 patients who met the criteria for HBV reactivation. Forty‐one practised outside the United States, and most were hepatologists (n = 71) or gastroenterologists (n = 12). One hundred and twenty‐six patients had haematologic malignancies, of which 88 (70%) had lymphoma. Seventy‐five patients (40%) had screening for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti‐HBc), and an additional 24 patients (13%) had HBsAg screening alone. Prophylactic antiviral therapy was reported in only 18 patients (10%). Chemotherapy was interrupted in 52 patients (41%) with haematologic malignancies and 26 of 41 patients (63%) with solid tumours (P = 0.01). Rituximab‐treated patients (n = 66) required hospitalization more frequently (P = 0.04), but their overall survival did not differ from individuals not treated with rituximab. Death due to liver failure was reported in 43 patients overall (23%). Underutilization of prophylactic antiviral therapy occured in a substantial number of patients who were found to be HBV infected prior to the initiation of cancer chemotherapy. The reasons for this need further exploration because reactivation results in serious yet preventable outcomes.     

Malignancy in scleroderma patients from south west England: a population-based cohort study

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient’s general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77–5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6–43, p = 0.03), especially for non-Hodgkin’s lymphoma (RR = 25.8, 95% CI 5–75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.     

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M‐HLH) in 21 patients, most of whom had T‐ (n = 12) or B‐cell neoplasms (n = 7), with Epstein–Barr virus as a co‐trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch‐HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M‐ and Ch‐HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M‐HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch‐HLH patients had evidence of active HLH. To overcome HLH, malignancy‐ and HLH‐directed treatments were administered in the M‐HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch‐HLH, treatment ranged from postponement of chemotherapy to the use of etoposide‐containing regimens.     

Safety and efficacy of sofosbuvir‐based direct‐acting antiviral regimens for hepatitis C virus genotype 6 in Southwest China: Real‐world experience of a retrospective study

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)‐based direct‐acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment‐naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF‐based DAAs therapy, including SOF 400 mg plus daclatasvir (DCV) 60 mg daily or SOF 400 mg plus velpatasvir (VEL) 100 mg daily for 12 weeks. The sustained virological response 12 weeks after treatment (SVR12) was 100% (60/60) in treatment‐naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P = 0.014) and week 24 (P < 0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase‐to‐platelet ratio index (APRI) and fibrosis‐4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P < 0.001). SOF‐based therapy was well‐tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment‐naïve patients with HCV GT6 without liver cirrhosis.     

Erectile dysfunction in cirrhosis is impacted by liver dysfunction,portal hypertension,diabetes and arterial hypertension

Background

Although several risk factors for erectile dysfunction may be present in patients with cirrhosis, data on the actual prevalence and cause of erectile dysfunction is limited. The International Index of Erectile Function‐5 (IIEF‐5) is a well‐validated survey to determine the presence and severity of erectile dysfunction in men. We assessed (i) the prevalence and severity of erectile dysfunction, and (ii) risk factors for erectile dysfunction in patients with cirrhosis.

Methods

In this prospective study, erectile dysfunction was defined as: absent (>21 IIEF‐5‐points), mild (12‐21) and severe (5‐11). Patients with overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy, previous urologic surgery, previous liver transplantation and severe cardiac conditions were excluded.

Results

Among n = 151 screened patients, n = 41 met exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n = 80 male patients with cirrhosis were included. Patient characteristics: age: 53 ± 9 years; model for end‐stage liver disease score (MELD): 12.7 ± 3.9; Child‐Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38 (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%) and 7 (8.8%) suffering from mild‐to‐moderate and moderate‐to‐severe erectile dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were significantly higher in patients with erectile dysfunction (P = .021; P = .028). Child‐Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low libido, low testosterone and high HVPG were associated with the presence of erectile dysfunction. Interestingly, beta‐blocker therapy was not associated with an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16‐34.85]; P = .033), diabetes (OR: 7.40 [1.31‐41.75]; P = .023), MELD (OR: 1.19 [1.03‐1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002‐1.23]; P = .045) were independent risk factors for the presence of erectile dysfunction.

Conclusion

About two‐thirds of male patients with cirrhosis show erectile dysfunction. Severity of liver dysfunction, portal hypertension, arterial hypertension and diabetes were identified as risk factors for erectile dysfunction.     

Early emergence of opportunistic infections after starting direct‐acting antiviral drugs in HIV/HCV‐coinfected patients

Varicella‐zoster virus and hepatitis B virus reactivations have been reported after starting interferon‐free direct‐acting antiviral agent (DAA) combinations. HIV/HCV‐coinfected patients could be a high‐risk group for the reactivation of latent infections. Because of these, we report the occurrence of severe infections after starting DAA regimens in HIV/HCV‐coinfected patients. Individuals included in the HEPAVIR‐DAA (NCT02057003) cohort were selected if they had received all‐oral DAA combinations. A retrospective review of clinical events registered between the start of DAAs and 12 months after SVR12 was carried out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95% confidence interval) of infections was 4.6 (3.3‐6.3) cases per 100 person‐years. The median (Q1‐Q3) time to the infection since baseline was 23 (7.3‐33) weeks. Five (13%) of the patients with infections died; four of them had cirrhosis. The frequency of previous AIDS was 21 (54%) for patients with infections and 324 (40%) for those without infections (P = 0.084). The median (Q1‐Q3) nadir CD4 cell count of individuals with and without infections was 75 (53‐178) and 144 (67‐255) cells/μL, respectively (P = 0.047). Immunodepression‐associated infections were observed in 9 (1.1%) patients. All of them had suppressed HIV replication with antiretroviral therapy. In conclusion, severe infections are relatively common among HIV/HCV‐coinfected patients receiving all‐oral DAA combinations. Some unusual reactivations of latent infections in patients with suppressed HIV replication seem to be temporally linked with DAA use.     

Hepatitis C virus infection in Australian psychiatric inpatients: A multicenter study of seroprevalence,risk factors and treatment experience

Screening and treatment for hepatitis C virus (HCV) infection were not prioritised in psychiatric patients due to adverse neuropsychiatric effects of interferon therapy despite reports of high prevalence. However, with the safe new antiviral drugs, HCV eradication has become a reality in these patients. The aim of this study was to report HCV seroprevalence, risk factors and treatment model in an Australian cohort. This prospective study involved patients admitted to four inpatient psychiatric units, from December 2016 to December 2017. After pretest counselling and consent, HCV testing was done; information on risk factors collected. A total of 260 patients (70% male), median age 44 years (IQR 24), were studied. The HCV seroprevalence was 10.8% (28/260) with 95% CI 7‐15. Independent predictors of HCV positivity were injection drug use (P < 0.001, OR 44.05, 95% CI 7.9‐245.5), exposure to custodial stay (P = 0.011, OR 7.34, 95% CI 1.6‐33.9) and age (P = 0.011, OR 1.09, 95% CI 1.02‐1.16). Eight of the 16 HCV RNA‐positive patients were treated. Hepatitis nurses liaised with community mental health teams for treatment initiation and follow‐up under supervision of hepatologists. Seven patients achieved sustained viral response, one achieved end of treatment response. The remaining eight patients were difficult to engage with. In conclusion, HCV prevalence was high in our cohort of psychiatric inpatients. Although treatment uptake was achieved only in 50% patients, it was successfully completed in all, with innovative models of care. These findings highlight the need to integrate HCV screening with treatment linkage in psychiatry practice.     

Liver transplant listing for hepatitis C‐associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct‐acting antiviral therapy

Following the introduction of direct‐acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)‐related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1‐year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV‐related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol‐related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV‐related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV‐related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV‐related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.     

Change in injecting behaviour among people treated for hepatitis C virus: The role of intimate partnerships

Injecting behaviour in people who inject drugs is the main risk factor for hepatitis C virus (HCV) infection. Psychosocial factors such as having a partner who injects drugs and living with other drug users have been associated with increases in injecting risk behaviour. This study aimed to investigate changes in injecting behaviour during treatment for HCV infection whilst exploring the role of psychosocial factors on patients’ injecting behaviour. Eradicate‐C was a single‐centred clinical trial (ISRCTN27564683) investigating the effectiveness of HCV treatment within the injecting drug‐using population between 2012 and 2017. A total of 94 participants completed up to 24 weeks of treatment, with social and behavioural measures taken at different intervals throughout treatment. Data for 84 participants were analysed retrospectively to explore mechanisms of potential behavioural changes which had occurred during treatment. Injecting frequency reduced significantly between baseline (week 1) and every 4‐weekly interval until week 26. Not being on opiate substitution therapy (OST) was associated with a statistically significant decrease in injecting frequency, χ² (1) = 10.412, P = 0.001, as was having a partner who also used drugs, in particular when that partner was also on treatment for HCV infection, Z = ?2.312, P = 0.021. Treating a hard‐to‐reach population for HCV infection is not only possible, but also bears health benefits beyond treatment of HCV alone. Enrolling couples on HCV treatment when partners are sero‐concordant has shown enhanced benefits for reduction in injecting behaviour. Implications for practice are discussed.     

Real‐world impact following initiation of interferon‐free hepatitis C regimens on liver‐related outcomes and all‐cause mortality among patients with compensated cirrhosis

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)‐free direct‐acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver‐related mortality and all‐cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day‐case hospitalization and deaths records, a study population comprising chronic HCV‐infected patients with compensated cirrhosis and initiated on IFN‐free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time‐dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child‐Pugh class. Among the study population (n = 1073) involving 1809 years of follow‐up, 75 (7.0%) died (39 from liver‐related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post‐treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05‐0.39), HCC (HR = 0.17; 95% CI: 0.04‐0.79), liver‐related death (HR = 0.13; 95% CI: 0.05‐0.34) and all‐cause mortality (HR = 0.30; 95% CI: 0.12‐0.76). Compared with responders, noncompliant patients had an increased risk of liver‐related (HR = 6.73; 95% CI: 2.99‐15.1) and all‐cause (HR = 5.45; 95% CI: 3.07‐9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing.     

Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population

The JAK2 V617F somatic mutation is present in the majority of patients with myeloproliferative cancer (polycythaemia vera, essential thrombocytosis, and primary myelofibrosis). However, the diagnostic value of the JAK2 V617F somatic mutation for myeloproliferative cancer in the general population is unknown. We examined this question in 49 488 individuals from the Copenhagen General Population Study. We also examined the association between JAK2 V617F somatic mutation, rs10974944 germline genotype, haematological phenotype, any cancer, haematological cancer, myeloproliferative cancer, ischaemic heart disease, and venous thromboembolism. The JAK2 V617F somatic mutation was present in 0·1% (n = 68), increasing across rs10974944 germline genotypes (P‐trend = 0·001). JAK2 V617F somatic mutation positives versus negatives had higher erythrocyte (P = 2 × 10⁻⁵), thrombocyte (P = 2 × 10⁻¹⁶), and leucocyte (P = 4 × 10⁻⁹) counts, and had 2·7‐/2·5‐fold risk of cancer (prevalent/incident), 44‐/28‐fold risk of haematological cancer, 221‐/97‐fold risk of myeloproliferative cancer, 2·2‐/1·2‐fold risk of ischaemic heart disease, and 3·1‐/1·0‐fold risk of venous thromboembolism. By combining conventional haematological parameters with a test for the JAK2 V617F somatic mutation, myelo;?>proliferative cancer could be identified or ruled out with a sensitivity of 47–100% and a specificity of 98–100%. In conclusion, in the general population the JAK2 V617F somatic mutation has a high diagnostic value for myeloproliferative cancer when combined with conventional haematological parameters.