Bruno Roche

Background Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations. Aims To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France. Methods This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy). Results Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy. Conclusions Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.

Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice.

Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20–30 % of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30 % of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75 % in genotype 1 infected patients. However, tolerability and drug–drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90 % in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug–drug interactions.

Antiviral therapy with interferon‐alpha (IFN‐alpha) and pegylated IFN‐alpha (PEG‐IFN‐alpha) for chronic hepatitis C (HCV)‐infected kidney recipients remains controversial. IFN‐alpha is not recommended in most cases because it induces severe acute graft rejection. However, IFN‐alpha, as PEG‐IFN‐alpha, is associated with a more pronounced immune response, and is well tolerated in HCV‐infected liver recipients without causing graft rejection. In combined liver–kidney transplant (LKT) recipients, IFN‐alpha has been occasionally used and appears to be well tolerated. All LKT recipients with a functioning kidney and liver having a HCV replication and who needed IFN‐alpha therapy have been included in the study. The occurrence of liver and/or renal acute rejection as well as the HCV replication has been collected. A total of 12 LKT patients treated with PEG‐IFN‐alpha plus ribavirin have been studied. No acute rejection was observed. Renal function remained stable during and after discontinuing treatment, without any graft dysfunction. Two patients had a partial viral response and four had a sustained viral response. All patients, whatever their viral response, had decreased liver‐enzyme levels. Response to PEG‐IFN‐alpha therapy was correlated with steroid dose and transaminase level when PEG‐IFN‐alpha was started. These data suggest that the combination therapy of PEG‐IFN‐alpha plus ribavirin did not have a higher risk of acute kidney‐graft rejection after liver–kidney transplantation.

Liver disease caused by the hepatitis C virus is the main indication for liver transplantation in Western countries. However, HCV re‐infection post‐transplantation is constant and recent data confirm that it significantly impairs patient and graft survival. Chronic HCV infection develops in 75–90% of patients, and 5–30% ultimately progress to cirrhosis within 5 years. Because of the impact of HCV recurrence on graft and patient survival, several treatment strategies have been evaluated. Antiviral therapy could be administered before transplantation to suppress viral replication and reduce the risk of recurrence. However, this approach is applicable in around 50% of patients and tolerance is poor, particularly in patients with decompensated cirrhosis. Pre‐emptive therapy in the early post‐transplant period is limited by the high rate of side effects. Frequently, antiviral therapy is initiated when HCV recurs to obtain viral eradication and/or reduce disease progression. Treatment of established graft lesions with Pegylated Interferon (PEG‐IFN) and Ribavirin (RBV) combination therapy results in a sustained virological response (SVR) in around 30% of patients. The new classes of potent and direct antiviral agents (DAA) will certainly improve the results of pre‐ and post‐transplant antiviral therapy. However, at the present time, no data are available on the use of these drugs in patients with decompensated cirrhosis or post‐transplant hepatitis.

Most cases of infections described after steroid treatment for severe acute alcoholic hepatitis are of bacterial origin. However, the rate of bacterial infections in these patients is not higher than in those who are not treated by steroids. The opportunistic infections are even more rare. We report two cases of patients with cirrhosis and human immunodeficiency virus, treated for alcoholic hepatitis with steroids and who subsequently developed severe pneumopathy due to Pneumocystis carinii. One patient had a concommitant cytomegalovirus infection and both of them died. Pneumocystis carinii infections usually occur in patients a decreased immune cellular response. Steroid treatments and also alcohol may be responsible for these opportunistic infections. Alcohol may have an immunosuppressive effect by decreasing recruitment of CD4 and CD8 lymphocytes to the lungs. In conclusion, Pneumocystis carinii pneumonia is a potential complication of steroid treatments for acute alcoholic hepatitis and should be suspected in case of unexplained pulmonary infection.