Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Trials ; 23(1): 302, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1789128

ABSTRACT

BACKGROUND: Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication. METHODS: The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021. DISCUSSION: The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis. TRIAL REGISTRATION: EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). CLINICALTRIALS: gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Multicenter Studies as Topic , Prospective Studies , Proton Pump Inhibitors/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
2.
Viruses ; 14(3)2022 02 25.
Article in English | MEDLINE | ID: covidwho-1765943

ABSTRACT

: Background:There are limited data available on the influence of direct-acting antivirals used to treat chronic hepatitis C (CHC) on growth in children. In this study, we aimed to analyze the growth parameters in children treated with ledipasvir/sofosbuvir (LDV/SOF). METHODS: We included38 patients (16 girls and 22 boys) aged 10-17 years treated with LDV/SOF for CHC (33 infected with genotype 1 and 5 with genotype 4; 36 were treated for 12 weeks, and 2 for 24 weeks according to the current guidelines). Patient weight and height were measured at baseline, after 4 weeks of treatment, at the end of the treatment (EOT), and 12 weeks and one year after the EOT. Body mass index (BMI), BMI z and height-for-age (HA) z scores were calculated according to the WHO Child Growth Standards and Growth reference data using the WHO anthropometric calculator AnthroPlus v. 1.0.4. In addition, correlations between BMI z scores and liver fibrosis (liver stiffness measurement, LSM), the aspartate transaminase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and liver steatosis (controlled attenuation parameter, CAP) were analyzed. RESULTS: At baseline, 5/38 (13%) patients were obese (BMI z score >2 SD), 4/38 (11%) were overweight, and 29 (76%) were normal. A significant increase was observed in mean weight, height and BMI both 12 weeks and one year after the treatment compared to the baseline, whereas no differences were observed for BMI z scores and HA z scores. Baseline BMI z scores correlated with alanine aminotransferase levels (r = 0.33, 95% CI 0.01-0.58, p =0.04), LSM (r = 0.40, 95% CI 0.09-0.65, p =0.01), the APRI (r = 0.33, 95% CI 0.02-0.59, p =0.03), and the CAP (r = 0.40, 95% CI 0.08-0.64, p =0.01). No similar correlations were reported at 12 weeks posttreatment. CONCLUSIONS: Treatment with LDV/SOF in children with CHC (genotypes 1 and 4) did not negatively influence the patients' growth. However, higher baseline BMI z scores correlated with more advanced liver fibrosis and steatosis in children with CHC.


Subject(s)
Hepatitis C, Chronic , Sofosbuvir , Adolescent , Antiviral Agents/therapeutic use , Benzimidazoles , Child , Drug Therapy, Combination , Female , Fluorenes , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/genetics , Humans , Liver Cirrhosis/drug therapy , Male , Sofosbuvir/therapeutic use , Treatment Outcome
3.
Nat Med ; 27(7): 1262-1271, 2021 07.
Article in English | MEDLINE | ID: covidwho-1550325

ABSTRACT

Preclinical and clinical data suggest that fibroblast growth factor 21 (FGF21) is anti-fibrotic, improves metabolic status and has potential to treat non-alcoholic steatohepatitis (NASH). We assessed the safety and efficacy of efruxifermin, a long-acting Fc-FGF21 fusion protein, for the treatment of NASH. BALANCED was a randomized, placebo-controlled study in patients with NASH conducted at 27 centers in the United States (ClinicalTrials.gov NCT03976401 ). Eighty patients, stratified by hepatic fat fraction (HFF) and fibrosis stage, were randomized using a centrally administered minimization algorithm 1:1:1:1 to receive placebo (n = 21) or efruxifermin 28 mg (n = 19), efruxifermin 50 mg (n = 20) or efruxifermin 70 mg (n = 20) via weekly subcutaneous injection for 16 weeks. The primary endpoint-absolute change from baseline in HFF measured as magnetic resonance imaging-proton density fat fraction at week 12-was met. For the full analysis set, the least squares mean absolute changes (one-sided 97.5% confidence interval) from baseline in HFF were -12.3% (-infinity (-inf), -10.3), -13.4% (-inf, -11.4) and -14.1% (-inf, -12.1) in the 28-, 50- and 70-mg groups, respectively, versus 0.3% (-inf, 1.6) in the placebo group, with statistically significant differences between efruxifermin groups and placebo (P < 0.0001 each). Overall, 70 of 79 patients who received the study drug (89%) experienced at least one treatment-emergent adverse event (TEAE), with the majority grade 1-2 (64 (81%)), five (6%) grade 3 and one grade 4. The most commonly reported drug-related TEAEs were grade 1-2 gastrointestinal (36 (46%)). Treatment with efruxifermin significantly reduced HFF in patients with F1-F3 stage NASH, with an acceptable safety profile.


Subject(s)
Fibroblast Growth Factors/therapeutic use , Immunoglobulin Fc Fragments/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Recombinant Fusion Proteins/therapeutic use , Body Mass Index , Double-Blind Method , Female , Humans , Liver/pathology , Liver Cirrhosis/drug therapy , Magnetic Resonance Imaging , Male , Middle Aged , Treatment Outcome
4.
World J Gastroenterol ; 27(42): 7362-7375, 2021 Nov 14.
Article in English | MEDLINE | ID: covidwho-1526867

ABSTRACT

BACKGROUND: Chronic liver disease, particularly cirrhosis, is associated with worse outcomes in patients infected with coronavirus disease 2019 (COVID-19). AIM: To assess outcomes of COVID-19 infection among patients with pre-existing hepatitis C with or without liver cirrhosis. METHODS: This multicenter, retrospective cohort study included all cases of confirmed co-infection of severe acute respiratory syndrome coronavirus 2 and chronic hepatitis C with or without liver cirrhosis who were admitted to six hospitals (Al-Sahel Hospital, Al-Matareya Hospital, Al-Ahrar Hospital, Ahmed Maher Teaching Hospital, Al-Gomhoreya Hospital, and the National Hepatology and Tropical Medicine Research Institute) affiliated with the General Organization for Teaching Hospitals and Institutes in Egypt. Patients were recruited from May 1, 2020, to July 31, 2020. Demographic, laboratory, imaging features, and outcomes were collected. Multivariate regression analysis was performed to detect factors affecting mortality. RESULTS: This retrospective cohort study included 125 patients with chronic hepatitis C and COVID-19 co-infection, of which 64 (51.20%) had liver cirrhosis and 40 (32.00%) died. Fever, cough, dyspnea, and fatigue were the most frequent symptoms in patients with liver cirrhosis. Cough, sore throat, fatigue, myalgia, and diarrhea were significantly more common in patients with liver cirrhosis than in non-cirrhotic patients. There was no difference between patients with and without cirrhosis regarding comorbidities. Fifteen patients (23.40%) with liver cirrhosis presented with hepatic encephalopathy. Patients with liver cirrhosis were more likely than non-cirrhotic patients to have combined ground-glass opacities and consolidations in CT chest scans: 28 (43.75%) vs 4 (6.55%), respectively (P value < 0.001). These patients also were more likely to have severe COVID-19 infection, compared to patients without liver cirrhosis: 29 (45.31%) vs 11 (18.04%), respectively (P value < 0.003). Mortality was higher in patients with liver cirrhosis, compared to those with no cirrhosis: 33 (51.56%) vs 9 (14.75%), respectively (P value < 0.001). All patients in Child-Pugh class A recovered and were discharged. Cirrhotic mortality occurred among decompensated patients only. A multivariate regression analysis revealed the following independent factors affecting mortality: Male gender (OR 7.17, 95%CI: 2.19-23.51; P value = 0.001), diabetes mellitus (OR 4.03, 95%CI: 1.49-10.91; P value = 0.006), and liver cirrhosis (OR 1.103, 95%CI: 1.037-1.282; P value < 0.0001). We found no differences in liver function, COVID-19 disease severity, or outcomes between patients who previously received direct-acting antiviral therapy (and achieved sustained virological response) and patients who did not receive this therapy. CONCLUSION: Patients with liver cirrhosis are susceptible to higher severity and mortality if infected with COVID-19. Male gender, diabetes mellitus, and liver cirrhosis are independent factors associated with increased mortality risk.


Subject(s)
COVID-19 , Coinfection , Hepatitis C, Chronic , Antiviral Agents/therapeutic use , Coinfection/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis/epidemiology , Male , Retrospective Studies , SARS-CoV-2
5.
In Vivo ; 35(6): 3377-3383, 2021.
Article in English | MEDLINE | ID: covidwho-1485630

ABSTRACT

BACKGROUND/AIM: Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS: We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS: Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION: Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/drug therapy , Liver Neoplasms/complications , Liver Neoplasms/drug therapy , Liver Neoplasms/epidemiology , Retrospective Studies , SARS-CoV-2
6.
Expert Rev Clin Pharmacol ; 14(4): 457-464, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1467264

ABSTRACT

INTRODUCTION: Galectin-3 (Gal-3) is a ß-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients. AREAS COVERED: This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials. EXPERT OPINION: Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.


Subject(s)
Blood Proteins/antagonists & inhibitors , Galectins/antagonists & inhibitors , Liver Cirrhosis/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Disease Models, Animal , Disease Progression , Humans , Liver Cirrhosis/metabolism , Liver Cirrhosis/physiopathology , Non-alcoholic Fatty Liver Disease/physiopathology , Pectins/administration & dosage , Pectins/pharmacology , Severity of Illness Index
7.
PLoS One ; 16(9): e0257369, 2021.
Article in English | MEDLINE | ID: covidwho-1416897

ABSTRACT

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/prevention & control , Australia/epidemiology , Calibration , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/mortality , Disease Progression , Epidemics , Epidemiological Monitoring , Hepacivirus , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/mortality , Humans , Incidence , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis/epidemiology , Liver Cirrhosis/mortality , Liver Neoplasms/complications , Liver Neoplasms/drug therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/mortality , Models, Theoretical , Prevalence , Treatment Outcome , World Health Organization
SELECTION OF CITATIONS
SEARCH DETAIL