Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In ...this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines’ Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.
A multiphase study was proposed to examine microbial communities linked to the nitrogen cycle in the first stage of four full-scale French vertical flow treatment systems. To this end, denaturing ...gradient gel electrophoresis (DGGE) was performed for structural assessment and quantitative PCR (qPCR) to enumerate the abundance of ammonia-oxidizing (AOB). 16S rRNA sequencing was used to assess the taxonomic profile followed by putative assessment of functional genes. The samples were collected under different conditions, such as operational time (presence/absence of sludge layer on the surface of the filters), season (winter and summer), sampling depth (0, 15 and 30 cm) and operation cycle (rest and feed periods). A structural disparity was noted in the upper layers, whereas higher similarity at 30 cm was observed highlighting the effect of organic matter on bacterial diversity. The 7th rest day was highlighted by an apparent decline in the microbial community abundance. Additionally, qPCR indicated that the largest amount of AOB was found at 30 cm depth and during the feeding period. From the taxonomic profile, Mycobacterium, Acinetobacter, Flavobacterium, and Nitrospira were the most abundant genre found in all systems. The functional prediction results showed predicted genes linked to the denitrification process. The results suggested that operating time and season were responsible for the pattern of the microbial community behavior. This study allowed us to further understand the bacterial dynamics and to advance the idea of design modifications made in the first stage of the classical French system to improve nitrogen removal are promising.
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•The performance of constructed wetlands of the French system was assessed.•Nitrogen removal by filters with a saturated layer was investigated.•Nitrification and denitrification were ...induced in a single VFCW stage.•Change of the inner water saturation level of the VFCWs was tested.•The effect of Eh and O2 concentrations on treatment performance was analyzed.
The objective of this research was to evaluate the nitrogen removal performance of vertical flow constructed wetlands implemented with a bottom saturated layer in the treatment of raw wastewater (French system). This research was carried out in two pilot systems over 16 months with different saturation depths (25cm and 15cm) to determine the optimal level for denitrification promotion. Monitoring included regular analysis of the physico-chemical parameters (TSS, dissolved COD, NH4+-N, TKN and NO3−-N) as well as online measurements (redox potential, oxygen and temperature, hydraulic behavior) to explain the filter’s behavior. Statistical performance analysis showed that a higher removal rate was obtained when the filters operated with 25cm saturation in comparison with 15cm saturation depth. The hydraulic study revealed the positive evolution of the system from the winter, where the clogging was observed, to the summer, where this phenomenon was not observed, demonstrating that the hydraulic conditions affect the nitrification efficiency. The redox potential measured at three different depths inside the filters clearly showed the variation in the Eh values as a function of the saturation level and feeding–resting cycles, indicating that such measurements are capable of revealing the existing biogeochemical processes in highly dynamic systems, such as constructed wetlands. The results demonstrated variations in performance according to the saturation condition and the system’s hydraulics; however, improvement of the design or the introduction of an additional treatment stage is necessary to achieve complete TN removal.
Preliminary studies on HCV‐cirrhotics listed for transplant suggest that sofosbuvir in combination with ribavirin is very effective in promoting viral clearance and preventing disease recurrence. ...Unfortunately, the high cost of such treatment (€46 500 per 12 weeks of treatment) makes its cost‐effectiveness questionable. A semi‐Markov model was developed to assess the cost‐effectiveness of sofosbuvir/ribavirin treatment in cirrhotic patients without HCC (HCV‐CIRRH) and with HCC (HCV‐HCC) listed for transplant. In the base‐case analysis, the incremental cost‐effectiveness ratio for 24 weeks of sofosbuvir/ribavirin was €44 875 per quality‐adjusted life‐year gained in HCV‐CIRRH and €60 380 in HCV‐HCC patients. Both results were above the willingness to pay threshold of €37 000 per quality‐adjusted life‐year. Our data also show that in order to remain cost‐effective (with a 24‐week treatment), any novel interferon‐free treatment endowed with ideal efficacy should cost less than €67 224 or €95 712 in HCV‐cirrhotics with and without HCC, respectively. The results shows that sofosbuvir/ribavirin therapy, given to patients listed for transplant, is not cost‐effective at current prices despite being very effective, and new, more effective treatments will have little economic margins to remain cost‐effective. New interferon‐free combinations have the potential to revolutionize the treatment and prognosis of HCV‐positive patients listed for transplant; however, without sustainable prices, this revolution is unlikely to happen.
The authors show that DAA‐based interferon‐free treatments in patients listed for transplantation are borderline cost‐effective at the current price, and the cost‐effectiveness estimates are critically influenced by the duration of treatment. See editorial by Brown on page 1741.
Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a ...detailed analysis of their effects in large studies is lacking.
Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis.
Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10–23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78–9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31–0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06–3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05–3.67) emerged as associated with death
Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.
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Summary
Different strategies of DAAs treatment are currently possible both pre‐ and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately ...investigated; this study aims at assessing their cost‐effectiveness. A decision analytical model was created to simulate the progression of HCV‐infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12‐week course of DAAs prior to transplantation (PRE‐LT), (ii) a 4‐week course of DAAs starting at the time of transplantation (PERI‐LT) and (iii) a 12‐week course of DAAs administered at disease recurrence (POST‐LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE‐LT treatment strategy was dominant for DCC patients with MELD<16 and cost‐effective for those with MELD16‐20, while POST‐LT strategy emerged as cost‐effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE‐LT as the cost‐effective strategy for patients with MELD≤20. In conclusion, PRE‐LT treatment is cost‐effective for patients with MELD≤20 without HCC, while treatments after LT are cost‐effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant‐related factors.
Summary
Long‐term functional outcomes of sofosbuvir‐based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for ...post‐transplant hepatitis C virus (HCV) recurrence. Seventy‐three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24‐week sofosbuvir with ribavirin±pegylated interferon or interferon‐free sofosbuvir‐based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82‐112) weeks. Twelve of 73 (16.4%) died (10 non‐FCH, 2 FCH) and two underwent re‐LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non‐FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow‐up, MELD and Child‐Turcotte‐Pugh scores improved both in non‐FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short‐treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long‐term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child‐Turcotte‐Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals‐based treatments for severe post‐transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long‐term survival. The setting of severe HCV recurrence may require the identification of “too‐sick‐to‐treat patients” to avoid futile treatments.
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