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BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l’Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child–Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

The integration of phototrophic microalgal production and anaerobic digestion can recycle excess nutrients across European surplus hotspots to produce protein-rich biomass for nutritional applications. However, the challenging physico-chemical properties of raw digestate constrain microalgal growth and limit digestate valorization potential. This study focused on the pre-treatment of food waste-based digestate using paper-filtration to improve its properties for cultivating Desmodesmus sp. and Chlorella vulgaris. The microalgal growth performance in paper-filtered digestate (PFD, 10 μm-pore size) was then compared to growth in membrane-filtered digestate (MFD, 0.2 μm-pore size). A microplate-based screening coupled with Cytation device assessment of PFD and MFD samples after dilution and with/without phosphorus supplementation showed that PFD was the best substrate. Moreover, phosphorus supplementation resulted in improved growth at higher digestate concentrations (5-10% v/v PFD), indicating the importance of using a balanced growth medium to increase the volumetric usage of digestate. Results were validated in a 3-L bioreactor at 10% PFD with phosphorus supplementation, reaching a biomass concentration of 2.4 g L

Obtaining a reliable estimation of the methane potential of organic waste streams in anaerobic digestion, for which a biochemical methane potential (BMP) test is often used, is of high importance. Standardization of this BMP test is required to ensure inter-laboratory repeatability and accuracy of the BMP results. Therefore, guidelines were set out; yet, these do not provide sufficient information concerning origin of and the microbial community in the test inoculum. Here, the specific contribution of the methanogenic community on the BMP test results was evaluated. The biomethane potential of four different substrates (molasses, bio-refinery waste, liquid manure and high-rate activated sludge) was determined by means of four different inocula from full-scale anaerobic digestion plants. A significant effect of the selected inoculum on the BMP result was observed for two out of four substrates. This inoculum effect could be attributed to the abundance of methanogens and a potential inhibiting effect in the inoculum itself, demonstrating the importance of inoculum selection for BMP testing. We recommend the application of granular sludge as an inoculum, because of its higher methanogenic abundance and activity, and protection from bulk solutions, compared with other inocula.

Single nucleotide polymorphisms (SNPs) in the proximity of the interleukin-28B (IL28B) gene can predict spontaneous resolution of hepatitis C virus (HCV) infection and response to interferon therapy. Screening for this polymorphism has become part of the standard criteria for the management of HCV-infected patients, hence the need for a rapid, cost-effective screening method. Here, we describe a rapid PCR-based test to screen for two IL28B SNPs (rs12979860 and rs8099917). We used this test to investigate IL28B polymorphism and prevalence in a cohort of French Canadian injection drug users who are part of a unique population known to have a strong genetic founder effect. This population had lower linkage disequilibrium between the two tested SNPs as compared to other cohorts (|d′| = 0.68, r = 0.59). The special genetic makeup should be considered in the management of HCV-infected patients within that population.

Background The once-daily fixed-dose combination tablet of sofosbuvir/velpatasvir/voxilaprevir(SOF/VEL/VOX) was evaluated for the treatment of genotype 1–6 HCV infection in four Phase 3 studies in direct-acting antiviral (DAA)-experienced (POLARIS-1 and POLARIS-4) and DAA-naive (POLARIS-2 and POLARIS-3) patients with and without compensated cirrhosis. DAA-experienced patients received treatment for 12 weeks, and DAA-naive patients received treatment for 8 weeks. Overall SVR12 rates were >95% across all the studies. This post-hoc analysis assesses efficacy in patients with and without traditional negative predictors of response. Methods This was a retrospective analysis of data from 1056 patients treated with SOF/VEL/VOX in the Phase 3 studies. Presence of cirrhosis was determined by histology, Fibrotest/APRI, or Fibroscan. Viral load and other clinical and laboratory assessments were determined prior to treatment with SOF/VEL/VOX. Prior treatment records were source verified, and race was self-reported by the patient to the investigator. Results Overall, 38% of patients had cirrhosis, 70% had HCV RNA ≥800,000 IU/mL, 59% of the DAA-experienced patients had received an NS5A inhibitor-containing regimen, 20% of the DAA-naive patients had prior treatment failure with pegylated interferon +ribavirin, 12% were ≥65 years old and 10% were black. Conclusions The POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4 studies enrolled a diverse patient population that included a significant number of patients with historically negative predictors of response including cirrhosis and prior exposure to DAA-containing regimens. High SVR12 rates for the ribavirin-free regimen of SOF/VEL/VOX were achieved across subgroups.

We and others have reported that adding adefovir dipivoxil (adefovir) to lamivudine results in virological and biochemical improvement in cases of lamivudine resistance. The current study assessed the efficacy and safety of combined therapy after 104 weeks of combined treatment and analyzed the frequency of persistent lamivudine resistant HBV.A total of 78 patients with compensated CHB (Group A) were maintained on either adefovir 10 mg daily (n = 38) or placebo (n = 40) while continuing lamivudine. An additional 38 patients with decompensated cirrhosis or post liver transplantation (Group B) received lamivudine plus adefovir. The primary endpoint was HBV DNA response at year 2.At week 104 of therapy, a significantly greater proportion of patients in Group A on combination therapy (76%) had a decline in serum HBV DNA to ≤10(5) copies or2 log(10) reduction from baseline compared to those receiving lamivudine alone (13%; p 0.001). Fifty-two percent of Group A patients on combination treatment continued to have the M204V/I HBV mutation compared to 92% receiving lamivudine alone (p = 0.0013). Virologic response occurred less frequently in patients expressing persistent lamivudine resistant HBV. In Group B, 87% of patients had HBV DNA response at week 104 (median change from baseline of -5.84 log(10) copies/mL).The combination of lamivudine and adefovir for 2 years generally proved effective in lamivudine-resistant cases, but there was a persistently high rate of detection of lamivudine resistant mutants and impaired virologic response in compensated patients.

Several biological ensilage additives were tested on maize substrate for their effect on biogas production and preservation of ODM content. In general, the addition of some biological additives and subsequent storage for 7 weeks could enhance the biogas and biomethane production per ODM when compared to the untreated sample. A common microbial inoculent containing homo-fermentative and heterofermentative bacteria (Bonsilage Mais ), had no beneficial effect on biogas and biomethane production compared with the non-treated sample (� 12.7% and � 13.1% per ODM, respectively). More complex additives with hetero- and homo-fermentative activity (Silasil Energy ) as well as enzymes (Sil-all 4 � 4) or bacteria and yeasts (Microferm) did effectively increase the biogas production per ODM (respectively with 11.8, 10.1 and 14.7%). Losses in ODM content were minor in all samples. These results might indicate that more divergent biological additives involving yeasts or enzymes during ensiling are preferred as maize preservation tools for anaerobic digestion instead of a spontaneous ensilage population or to add only homo- and hetero-fermentative strains. The nature of the additive might enhance the hydrolysis step in the anaerobic digestion process by decomposing complex carbohydrate structures. 2010 Elsevier Ltd. All rights reserved.

Modelling is increasingly used for optimizing environmental treatment processes such as anaerobic digestion. It allows problems such as instability of the process to be solved by predicting various scenarios. The anaerobic digestion model No. 1 (ADM1) is accepted worldwide as the standard model for the description of anaerobic digestion. However, it is sophisticated and complex, so it is not user friendly. Therefore, a mathematical method was developed that allows the calculation of the reactor pH, as well as the biogas flow rate (Q) and composition (expressed as the CO2 partial pressure, pCO2), based on a small number of widely available analyses such as chemical oxygen demand and total organic carbon. Furthermore, the ADM1 model was originally designed for anaerobic digestion of wastewater. In this work, the ADM1 model is evaluated for the first time for application in the modelling of solid waste digestion. This evaluation was performed in two steps. First, a list of experimentally available lab-scale data (pH and Q) was grouped according to the composition and origin of the treated solid waste (e.g. manure or vegetable waste). For each group the developed model for the calculation of pH, Q and pCO2 was calibrated with this lab-scale data. After calibration, the model was validated with additional experimental results. It could be demonstrated statistically that the model was able to predict the experimental results, although the confidence region was rather large.

Plant-virus-based vaccines have emerged as a promising avenue in vaccine development. This report describes the engineering of an innovative vaccine platform using the papaya mosaic virus (PapMV) capsid protein (CP) as a carrier protein and a C-terminal fused hepatitis C virus (HCV) E2 epitope as the immunogenic target. Two antigen organizations of the PapMV-based vaccines were tested: a virus-like-particle (VLP; PapMVCP-E2) and a monomeric form (PapMVCP27–215-E2). While the two forms of the vaccine were both shown to be actively internalized in vitro in bone-marrow-derived antigen presenting cells (APCs), immunogenicity was demonstrated to be strongly dependent on antigen organization. Indeed, C3H/HeJ mice injected twice with the multimeric VLP vaccine showed a long-lasting humoral response (more than 120 days) against both the CP and the fused HCV E2 epitope. The antibody profile (production of IgG1, IgG2a, IgG2b, IgG3) suggests a Th1/Th2 response. Immunogenicity of the PapMV vaccine platform was not observed when the monomer PapMVCP-E2 was injected. These results demonstrate for the first time the potential of the PapMV vaccine platform and the critical function of multimerization in its immunogenicity.

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA 600,000 IU/mL, 95% CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon α-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment. (HEPATOLOGY 2006;43:954–960.)

Background The once-daily fixed-dose combination tablet of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) was evaluated for the treatment of genotype 1–6 HCV infection in four phase 3 studies in patients with and without compensated cirrhosis. This analysis describes the safety of SOF/VEL/VOX across 4 Phase 3 studies. Methods Treatment-emergent adverse events (AEs) and laboratory abnormalities were assessed in patients who received SOF/VEL/VOX or placebo for 12 weeks (POLARIS-1), SOF/VEL/VOX or SOF/VEL for 12 weeks (POLARIS-4), or SOF/VEL/VOX for 8 weeks or SOF/VEL for 12 weeks (POLARIS-2 and POLARIS-3). SAEs and deaths were followed until post-treatment Week 24. Data were pooled by treatment regimen. Results 1056 patients were treated with SOF/VEL/VOX for 8 (n=611) or 12 (n=445) weeks, 700 received SOF/VEL for 12 weeks. 38% had compensated cirrhosis, 28% had a BMI≥30 kg/m2, 36% were female, and 12% were ≥65 years old. AEs are presented in the table. Two deaths were reported, one illicit drug overdose and one attributed to hypertension (on post-treatment Day 76), neither were related to treatment. SAEs and discontinuations were more frequent in the placebo group and occurred with similar frequency in the other groups; none were related to study treatment. Headache, fatigue, nausea, and diarrhoea were the most common AEs. Mild diarrhoea and nausea occurred more frequently in the SOF/VEL/VOX groups. Overall, 5.1%–6.6% of patients who received SOF/VEL/VOX or SOF/VEL had Grade 3 or 4 laboratory abnormalities. Among patients receiving VOX, one patient each had a Grade 3 elevation in ALT and bilirubin (table 1). Conclusions SOF/VEL/VOX for 8 or 12 weeks in the POLARIS studies was well tolerated with a low frequency of Grade 3 or 4 AEs, SAEs, and AEs leading to discontinuation. The frequency of AEs in the SOF/VEL/VOX groups was similar to SOF/VEL and placebo groups, with higher rates of mild diarrhoea and nausea compared to SOF/VEL. References 1. Time to get control. A review of the care received by patients who had a severe gastrointestinal haemorrhage. NCEPOD 2015. 2. Shaheen AAM, Kaplan GG, Myers RP.Weekend versus weekday admissions and mortality from gastrointestinal haemorrhage caused by peptic ulcer disease. Clinical Gastroenterology and Hepatology2009;7:303–310.

The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a "breakthrough" while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-alpha2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P =.014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

The purpose of this study was to evaluate the prognostic value of clinical measures of the severity of disease in cirrhotic patients who were candidates for liver transplantation at our institution. The records of the 132 cirrhotic patients who were candidates for a first transplantation between January 1, 1987, and December 31, 1994, were reviewed. One hundred nine patients (82.6%) received grafts, and 23 (17.4%) died while on the waiting list. The variables examined included level of medical urgency at the time of enlistment, date of transplantation, serum creatinine level, variables that constitute the Child-Pugh score and Shaw's risk score (serum bilirubin and albumin, prothrombin time, ascites, encephalopathy, nutritional status, age, and operative blood loss), and 6-month survival status after transplantation. The proportion of patients who died awaiting a graft increased as a function of the Child-Pugh score at enlistment (score 5-6, 0%, n = 6; score 7-9, 7%, n = 54; score 10-11, 18%, n = 33; score 12-15, 33%, n = 39; P = .01). Six-month survival rates after transplantation were similar irrespective of the Child-Pugh score or Shaw's risk score. Stepwise multiple logistic regression models identified the degree of ascites, serum bilirubin, and operative blood loss as significant variables for the prediction of overall mortality 6 months posttransplantation (model chi 2 = 12.8; P = .025; r = 0.32), but the model explained only 10% of the outcomes observed. We concluded that the Child-Pugh score is a valid prognostic index for survival up to the time of transplantation for cirrhotic patients on the waiting list; however, clinical measures of the severity of cirrhosis are poor predictors of 6-month survival after transplantation.

Cirrhotic livers obtained from eight patients who underwent orthotopic liver transplantation were perfused through the portal vein and hepatic artery in a closed recycling system for periods ranging from 2 to 7 hr. An average perfusion flow of 451 ml/min was used, with about 80% coming from the portal vein and 20% from the hepatic artery. The livers appeared to remain viable as assessed by gross appearance, stable portal vein and hepatic artery pressures, oxygen consumption and bile production. The extraction ratio of indocyanine green by the perfused livers averaged 0.098 (range = 0.023 to 0.168); that of propranolol averaged 0.445 (range = 0.126 to 0.813). Using the multiple-indicator dilution-curve method, shunts greater than 15 microns in diameter were demonstrated between the portal and hepatic veins in six of eight cases, whereas shunts from the hepatic artery to the hepatic veins were absent. Perfusion of human livers obtained during hepatic transplantation is a fairly simple procedure that will allow researchers to gain new insights into cirrhosis in humans.

Virological response to treatment of chronic hepatitis B is defined as the loss of serum hepatitis B virus DNA (HBV DNA) and hepatitis B e antigen (HBeAg). The quantitative measurement of HBV DNA is useful for monitoring and predicting the response to therapy with interferon-alpha (IFN-alpha). In this study, we evaluated whether quantitative measurement of serum HBeAg and IgM antibody to hepatitis B core antigen (HBcAb) could also be used in this manner. Using a microparticle-capture enzyme immunoassay (IMx), a standard curve of fluorescence rate vs HBeAg concentration was constructed to provide quantitative results. The IgM HBcAb index was also measured using a microparticle enzyme immunoassay and serum HBV DNA was measured by a solution hybridization assay. We studied 48 patients who were initially positive for HBeAg and HBV DNA and who were treated with IFN-alpha2b. Their sera were serially evaluated for HBeAg concentration, and results were compared with HBV DNA levels. In the 14 patients who responded to IFN, similar disappearance curves were observed with good intraindividual correlation between the levels of the two markers. In the 34 non-responders, HBeAg levels decreased during treatment but never became negative; HBV DNA levels also decreased during treatment and became transiently undetectable in six patients, falsely suggesting treatment success. The IgM HBcAb index paralleled changes in alanine aminotransferase (ALT) concentration and did not provide additional information. Multiple logistic regression indicated that baseline ALT and HBeAg concentrations were independent predictors of the response to treatment and the addition of neither HBV DNA nor IgM HBcAb improved the model. We conclude that quantitative measurement of HBeAg provides information similar to that of HBV DNA in monitoring and predicting the response to treatment; this technique could be readily adaptable to clinical laboratories.

We conducted a prospective, randomized single-blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy-nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty-seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child-Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B, and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. beta-blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liver disease.