LB01 SIX WEEKS OF SOFOSBUVIR/LEDIPASVIR TREATMENT OF ACUTE HEPATITIS C VIRUS GENOTYPE 1 MONOINFECTION: FINAL RESULTS OF THE THE GERMAN HEPNET ACUTE HCV IV STUDY

Abstract

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is highly effective but is associated with frequent unfavorable side effects. There is no fully published study yet exploring the safety, efficacy and required treatment duration of interferon‐free treatment of acute hepatitis C virus monoinfection. Preliminary reports suggested that ledipasvir/sofosbuvir therapy is effective in acute hepatitis C but relapses were reported in HIV‐coinfected patients after 6 weeks of treatment. The German HepNet Acute HCV IV Study was designed as a single‐arm, prospective multicenter pilot study to evaluate the efficacy and safety of treatment with sofosbuvir plus ledipasvir (SOF/LDV) for 6 weeks without ribavirin in patients with acute genotype 1 HCV monoinfection. We here report the final 24 weeks’ post‐treatment results. Twenty patients were included by 10 centers (60% male, mean age 46 ± 12 years; 11 patients HCV genotype 1a, 9 patients genotype 1b). The main risk factors for HCV infection were sexual transmission (n = 11) and medical procedures/needle stick injuries (n = 5). Median alanine aminotransferase (ALT) and median bilirubin levels before start of antiviral treatment were 225 U/l (range 32–2716) and 13.6 µmol/l (range 5.13–111), respectively. ALT levels rapidly declined during therapy and values normalized already by treatment weeks 2 in nine patients and by week 4 in 17 patients. HCV RNA was undetectable by the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0 by weeks 2, 4 and 6 in eight, 13, and 20 patients, respectively. SVR‐12 was 100% and 19 patients have completed FU‐week 24 and all remained HCV‐RNA negative. One patient was lost to follow‐up at week 24 post treatment. Treatment for 6 weeks with LDV/SOF was well tolerated and highly effective in HCV genotype 1 monoinfected patients with acute hepatitis C. Virological response was durable after therapy for at least 24 weeks. A rapid improvement in biochemical disease activity was observed during therapy. Short‐duration treatment of acute hepatitis C could prevent the spread of HCV in high‐risk populations and may be cost‐saving as compared with treatment of chronic hepatitis C. Katja Deterding: Lecturer fees and travel grants from Gilead, MSD/Merck and AbbVie Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials,1 but real‐life data are still needed in order to confirm this profile.2 In Romania, through a governamental programme, approx. 5000 patients with virus C compensated liver cirrhosis will receive reimbursed DAA with Paritaprevir/Ombitasvir/ritonavir, Dasabuvir with Ribavirin for 12 weeks during 2015–2016. We analysed a national prospective cohort enrolling 654 patients who started the therapy in December 2015–January 2016. All patients had genotype 1b. The only key inclusion criteria was Child‐Pugh score ⩽6. Only serious adverse events leading to discontinuation of therapy were reported. Data were obtained from the National Health Insurance House. Efficacy was assessed by the percentage of patients achieving SVR (HCV RNA undetectable) 12 weeks post‐treatment (SVR12). Ordinal and scale variables with non‐normal distribution were summarized as median (min, max), and compared by Mann–Whitney U test, while categorical variables were summarized as number (%) and compared by Fisher exact test. Two patients were lost to follow‐up because of adverse events probably not related to therapy, eight stopped the treatment because of hepatic decompensation (1.2%), one patient stopped because of severe arrythmia (drug–drug interaction involved). This cohort was 46% females, mean age 58.16 years (35–79), 67% pre‐treated with Peg‐Interferon+ Ribavirin, 70% associated NASH, 72% with severe necro‐inflammatory activity (severity score 3‐ Fibromax), 30% with co‐morbidities, 11.8% with Child Pugh A 6 points, 10 with virus B co‐infection (all of them with HBV‐DNA viral load below 20 IU/ml). The mean MELD (model for end stage liver disease) score was 6.15 ± 3.01 (0.5–20). SVR was reported in 641/644 (99.53%), 3/644 relapsed. Due to the small sample of patients it was not possible to identify predictive factors for viral response. Liver decompensation was statistically associated with higher BMI (body mass index) (p = 0.029), higher bilirubin (p = 0.001), higher MELD score (p = 0.001) and lower platelet count (p = 0.005). Paritaprevir/Ombitasvir/ritonavir, Dasabuvir with Ribavirin proved to be highly efficient in our population of cirrhotics with a 99.53% SVR. Serious adverse events related to therapy were reported in 9/641 (1.4%), most of them liver decompensation (1.2%), for which we identified the following risk factors: higher IMC, higher bilirubin, higher MELD score and lower platelet count. *These data are the property of the Romanian government. Single port laparoscopic surgery as an alternative to standard laparoscopy in patients undergoing cholecystectomy for benign disease has not yet been accepted as standard procedure. The aim of the MUlti‐port versus SIngle‐port Cholecystectomy (MUSIC) trial was to compare single access (SPC) with standard laparoscopy (MPC) in terms of morbidity. A non‐inferiority phase 3 trial was undertaken at 20 centres and hospitals in six countries. Patients requiring cholecystectomy were randomly assigned to either SPC or MPC, in each centre. Primary outcome was overall morbidity within 60 days from surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT01104727. The study was undertaken between April 2011 and May 2015. Six hundred patients were randomly assigned to SPC (n = 297) and MPC (n = 303), and were eligible for analyses. Thirteen patients (4.7%) in the SPC group experienced complications within 60 days after surgery, compared with 16 (6.1%) in the MPC group (p = 0.468); however, single access procedures took longer (70 min [25–265] vs. 55 min [22–185]; p < 0.001). No difference in hospital stay and perception of pain was observed. Six patients experienced an incisional hernia at 1 year in the SPC group, compared with three in the MPC group (p = 0.331). While patients better appreciated their cosmetic results in the SPC group, plastic surgeons were in favour of the cosmetic results in the MPC group. No difference in Quality of Life score was assessed by GIQLI at 60 days was observed. In selected patients with benign gall bladder disease requiring cholecystectomy, single access technique is non‐inferior to standard laparoscopy in terms of safety, despite a longer operative time required. While concerns about possible increase of risk of incisional hernias following SPC are not justified, cosmetic results were perceived better in the single access technique. All authors have declared no conflicts of interest. The influence of comorbidity on haemorrhagic complications in cholecystectomy is insufficiently known. Furthermore, the need for cessation of prescription drugs in order to reduce haemorrhagic complications is still a matter of debate. All cholecystectomies registered in the Swedish population‐based Register for Gallstone Surgery and ERCP (GallRiks) were identified. The effect of comorbidity and prescribed drugs on bleeding was assessed by linking data in the GallRiks to the National Patient Register and the Prescribed Drug Register respectively. The risk for haemorrhage leading to intervention was determined by variable regression, and Kaplan–Meier analysis assessed survival rate following perioperative haemorrhage. A total of 94,557 patients were included between 2005 and 2015, of which 799 (0.8%) and 1192 (1.3%) patients were registered as having perioperative and postoperative haemorrhage, respectively. An increased risk for haemorrhagic complications was seen in patients with kidney disease, previous myocardial infarction, heart failure, cerebrovascular disease and obesity (all p < 0.05). Prescription of tricyclic antidepressant or dipyridamole was associated with a significantly increased risk for perioperative haemorrhage (p < 0.05). However, this increase in risk did not remain significant following Bonferroni correction for mass significance. Perioperative haemorrhage increased the risk of death occurring within the first postoperative year [Hazard Ratio, (HR): 4.9, CI: 3.52–6.93] as well as bile duct injury (OR: 2.45, CI: 1.79–3.37). The increased risk for haemorrhage associated with comorbidity must be taken into account when assessing patients prior to cholecystectomy. Perioperative bleeding increases postoperative mortality and is associated with an increased risk for bile duct injury. The Mayo Clinic recently presented a new staging system that is applicable to all patients with perihilar cholangiocarcinoma (PHC) regardless of subsequent treatment.1 The staging system assigns patients to one of four stages, depending on the patients' performance status, serum CA19‐9 level, and radiological parameters including tumor size, suspected vascular involvement, and metastatic disease. We aimed to validate this staging system. All consecutive patients with PHC who were evaluated and treated in two tertiary centers between January 2002 and December 2014 were identified. Baseline characteristics required for the prognostic model were collected from medical records and imaging parameters were reassessed by experienced abdominal radiologists. Overall survival (OS) was analyzed using the Kaplan–Meier method and comparison of staging groups was performed using the log‐rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance (C)‐index. Subgroup analysis was performed for treatment subgroups. A total of 600 patients were staged according to the Mayo Clinic model, allocating 23, 80, 357 and 140 patients to stages I, II, III and IV, respectively. Median OS was 11.6 months. Median OS of stages I, II, III and IV was 33.2, 19.7, 12.1