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Journal of Clinical Gastroenterology Jul 2024Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and... (Meta-Analysis)
Meta-Analysis
Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.
Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.
Topics: Humans; Hepatitis, Autoimmune; Acute-On-Chronic Liver Failure; Prevalence; Treatment Outcome
PubMed: 38847808
DOI: 10.1097/MCG.0000000000002022 -
Cureus Apr 2024In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a... (Review)
Review
In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a global increase in cases, understanding the pattern of liver injury in AHUO is crucial to properly identify cases of this unexplained phenomenon, especially since it occurred simultaneously with a global resurgence of COVID-19. The objective of this study was to contrast the patterns in liver-relevant biochemical data from COVID-19 patients and AHUO. Studies reporting liver chemistries for cases of AHUO and COVID-19 were identified by a systematic review and search of the literature. For each case, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, and international normalized ratio (INR) levels were extracted as available. These were normalized to multiples of the upper limit of normal by patient age. There were statistically significant greater elevations of ALT and AST in patients with AHUO than in those with COVID-19. Only a subset of patients with COVID-19 had an AST or ALT greater than the normal range. INR elevation could be substantial for both conditions but was also statistically higher in the AHUO group. Liver chemistry changes were not statistically correlated with age. The pattern of liver chemistry changes between AHUO and COVID-19 have some distinctions, which suggests that AHUO is not a phenomenon driven primarily by SARS-CoV-2 infection alone. Differentiating AHUO and COVID-19 would be challenging based on patterns of liver chemistry changes alone.
PubMed: 38752102
DOI: 10.7759/cureus.58307 -
Journal of Clinical Medicine Feb 2024HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail... (Review)
Review
HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.
PubMed: 38592036
DOI: 10.3390/jcm13051210 -
Conflict and Health Apr 2024Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which... (Review)
Review
BACKGROUND
Conflict situations, armed or not, have been associated with emergence and transmission of infectious diseases. This review aims to identify the pathways through which infectious diseases emerge within conflict situations and to outline appropriate infectious disease preparedness and response strategies.
METHODS
A systematic review was performed representing published evidence from January 2000 to October 2023. Ovid Medline and Embase were utilised to obtain literature on infectious diseases in any conflict settings. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis). No geographical restrictions were imposed.
FINDINGS
Our review identified 51 studies covering AIDS, Hepatitis B, Tuberculosis, Cholera, Coronavirus 2, Ebola, Poliomyelitis, Malaria, Leishmaniasis, Measles, Diphtheria, Dengue and Acute Bacterial Meningitis within conflict settings in Europe, Middle East, Asia, and Africa since October 2023. Key factors contributing to disease emergence and transmission in conflict situations included population displacement, destruction of vital infrastructure, reduction in functioning healthcare systems and healthcare personnel, disruption of disease control programmes (including reduced surveillance, diagnostic delays, and interrupted vaccinations), reduced access by healthcare providers to populations within areas of active conflict, increased population vulnerability due to limited access to healthcare services, and disruptions in the supply chain of safe water, food, and medication. To mitigate these infectious disease risks reported preparedness and response strategies included both disease-specific intervention strategies as well as broader concepts such as the education of conflict-affected populations through infectious disease awareness programmes, investing in and enabling health care in locations with displaced populations, intensifying immunisation campaigns, and ensuring political commitment and intersectoral collaborations between governments and international organisations.
CONCLUSION
Conflict plays a direct and indirect role in the transmission and propagation of infectious diseases. The findings from this review can assist decision-makers in the development of evidence-based preparedness and response strategies for the timely and effective containment of infectious disease outbreaks in conflict zones and amongst conflict-driven displaced populations.
FUNDING
European Centre for Disease Prevention and Control under specific contract No. 22 ECD.13,154 within Framework contract ECDC/2019/001 Lot 1B.
PubMed: 38584269
DOI: 10.1186/s13031-023-00568-z -
Acta Diabetologica Jul 2024Post-transplant diabetes is a prevalent and consequential complication following kidney transplantation, which significantly augments the risk of cardiovascular disease,... (Meta-Analysis)
Meta-Analysis
AIMS
Post-transplant diabetes is a prevalent and consequential complication following kidney transplantation, which significantly augments the risk of cardiovascular disease, graft loss, infection, and mortality, thereby profoundly impacting both graft and patient survival. However, the early stages of post-transplant diabetes often go unnoticed or receive inadequate management. Consequently, this study systematically assesses the incidence of new-onset diabetes after kidney transplantation with the aim to enhance medical staff awareness regarding post-transplantation diabetes and provide clinical management guidance.
METHODS
We conducted a comprehensive search across multiple databases including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed until September 21, 2023. Data extraction was performed using standardized tables and meta-analysis was conducted using Stata 16.0 software. A random effects model was employed to estimate the combined prevalence along with its corresponding 95% confidence interval. The source of heterogeneity was explored using subgroup analysis and sensitivity analysis, while publication bias was assessed through funnel plot and Egger's test. This study has been registered with PROSPERO under the registration number CRD42023465768.
RESULTS
This meta-analysis comprised 39 studies with a total sample size of 16,584 patients. The prevalence of new-onset diabetes after transplantation was found to be 20% [95% CI (18.0, 22.0)]. Subgroup analyses were conducted based on age, gender, body mass index, family history of diabetes, type of kidney donor, immunosuppressive regimen, acute rejection episodes, hepatitis C infection status and cytomegalovirus infection.
CONCLUSIONS
The incidence of post-kidney transplantation diabetes is substantial, necessitating early implementation of preventive and control measures to mitigate its occurrence, enhance prognosis, and optimize patients' quality of life.
CLINICAL TRIAL REGISTRATION
PROSPERO: CRD42023465768.
Topics: Humans; Diabetes Mellitus; Kidney Transplantation; Postoperative Complications; Prevalence
PubMed: 38507083
DOI: 10.1007/s00592-024-02253-w -
Journal of the International AIDS... Mar 2024Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
INTRODUCTION
Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell.
METHODS
We searched two databases and conference abstracts from January 2015 to December 2022 for studies which reported reasons for disengagement from ART care. We included quantitative (mainly surveys) and qualitative (in-depth interviews or focus groups) studies conducted after "treat all" or "Option B+" policy adoption. We used an inductive approach to categorize reasons: we report how often reasons were reported in studies and developed a conceptual framework for reasons.
RESULTS
We identified 21 studies which reported reasons for disengaging from ART care in the "Treat All" era, mostly in African countries: six studies in the general population of persons living with HIV, nine in pregnant or postpartum women and six in selected populations (one each in people who use drugs, isolated indigenous communities, men, women, adolescents and men who have sex with men). Reasons reported were: side effects or other antiretroviral tablet issues (15 studies); lack of perceived benefit of ART (13 studies); psychological, mental health or drug use (13 studies); concerns about stigma or confidentiality (14 studies); lack of social or family support (12 studies); socio-economic reasons (16 studies); health facility-related reasons (11 studies); and acute proximal events such as unexpected mobility (12 studies). The most common reasons for disengagement were unexpected events, socio-economic reasons, ART side effects or lack of perceived benefit of ART. Conceptually, studies described underlying vulnerability factors (individual, interpersonal, structural and healthcare) but that often unexpected proximal events (e.g. unanticipated mobility) acted as the trigger for disengagement to occur.
DISCUSSION
People disengage from ART care for individual, interpersonal, structural and healthcare reasons, and these reasons overlap and interact with each other. While HIV programmes cannot predict and address all events that may lead to disengagement, an approach that recognizes that such shocks will happen could help.
CONCLUSIONS
Health services should focus on ways to encourage clients to engage with care by making ART services welcoming, person-centred and more flexible alongside offering adherence interventions, such as counselling and peer support.
Topics: Adolescent; Female; Humans; Male; Pregnancy; Anti-Retroviral Agents; Developing Countries; HIV Infections; Sexual and Gender Minorities; Medication Adherence; Patient Dropouts
PubMed: 38494657
DOI: 10.1002/jia2.26230 -
Cureus Jan 2024Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to... (Review)
Review
Dialysis in pediatric groups is complicated by a wide range of factors that can affect long-term prognosis. The purpose of this meta-analysis and systematic review is to better understand the demographic and clinical factors that affect dialysis success in children. We searched a variety of databases for relevant articles and included 14 reports that dealt with the case studies of pediatric patients undergoing dialysis for a wide range of renal diseases. Patients' demographics, clinical presentations, laboratory findings, and treatment outcomes were the primary areas of data collection. To get a better sense of the overall prevalence of certain outcomes and to spot noteworthy trends or patterns in the disease process, we conducted a meta-analysis. Variations in dialysis efficacy and outcomes are highlighted throughout a wide range of ages in the pediatric dialysis cohort, from neonates to teenagers. Acute kidney injuries (AKI) tended to impact more boys, but chronic kidney diseases (CKD), such as lupus nephritis, disproportionately afflicted girls. Many different ethnic groups were represented, and there was evidence that some diseases having a hereditary component were more common in some areas than others. However, the potential for long-term consequences remained a concern. Hemodialysis was found to be effective in controlling end-stage renal disease (ESRD) and AKI, with some patients going on to have a kidney transplant. At the same time, peritoneal dialysis was associated with an increased risk of infection. This comprehensive analysis highlights the importance of demographic and clinical parameters in determining pediatric dialysis outcomes. A 14.47% mortality rate and gender disparities are revealed by this meta-analysis of pediatric renal diseases, which included a cohort of 235 patients with conditions like lupus nephritis and hepatitis C infection. The findings stress the necessity for individualized treatment techniques and suggest that demographic characteristics should be addressed in prognostic models. For better patient outcomes, the study also suggests standardized reporting in pediatric dialysis studies.
PubMed: 38344624
DOI: 10.7759/cureus.51978 -
Journal of Clinical Medicine Jan 2024Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal... (Review)
Review
Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, = 34). SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.
PubMed: 38256491
DOI: 10.3390/jcm13020357 -
The Cochrane Database of Systematic... Jan 2024Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and...
BACKGROUND
Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome.
OBJECTIVES
To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023.
SELECTION CRITERIA
We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation. We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years). We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I = 78%; very low-certainty evidence). The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I = 0%; low-certainty evidence). We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I = 0%; very low-certainty evidence) or on the length of hospitalisation (MD -20.0 days, 95% CI -39.92 to -0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence). No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement. Funding No trials reported sources of commercial funding or conflicts of interest between researchers. Ongoing studies We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found.
AUTHORS' CONCLUSIONS
TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.
Topics: Adult; Humans; Albumins; Ascites; Brain Diseases; Hepatorenal Syndrome; Peritonitis; Portasystemic Shunt, Transjugular Intrahepatic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38235907
DOI: 10.1002/14651858.CD011039.pub2 -
Revista Espanola de Enfermedades... Jan 2024Research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced...
BACKGROUND
Research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced varied results, and the determinants of the immunological response remain largely elusive.
METHODS
A comprehensive search of three primary databases (PubMed, Embase, and Web of Science) yielded pertinent studies on the topic. The data extraction was a collaborative effort among three independent researchers, who subsequently reconvened to validate the key data that were collated. The primary outcomes were the magnitudes of humoral and cellular immune responses to the vaccines. The secondary outcomes were related to factors affecting the humoral immune response post-vaccination.
RESULT
Our systematic review incorporated eight studies, and the meta-analysis involved three. The average antibody response rates after one, two, and three doses of the SARS-CoV-2 vaccine were 86%, 82%, and 91%, respectively. Unexpectedly, the antibody concentrations of seropositive patients were markedly lower than those of their healthy counterparts. The cellular immune response rates after two and three vaccine doses were 74% and 56%, respectively. Treatment with mycophenolate mofetil and corticosteroids was associated with a notable decrease in seropositivity [pooled odds ratio (95% confidence interval): 2.62 (2.12-3.25) and 2.4 (1.51-3.82), respectively]. In contrast, azathioprine had no discernable impact on the humoral response.
CONCLUSION
In patients with AIH, the immune response to COVID-19 vaccination is attenuated. Specific immunosuppressive agents, such as steroids and MMF, have been found to reduce antibody responses. Recognizing these determinants is foundational to formulating individualized vaccination strategies for patients with AIH. Further research with an emphasis on post-vaccination cellular immunity will be essential to refine the vaccination approaches for this demographic.
PubMed: 38235657
DOI: 10.17235/reed.2024.10053/2023