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Przeglad Gastroenterologiczny 2022There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF). (Review)
Review
INTRODUCTION
There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF).
AIM
To determine whether NAC is beneficial in non-acetaminophen ALF.
MATERIAL AND METHODS
We performed a systemic review and meta-analysis of published data to address the question. PubMed and MEDLINE were searched using the terms non-acetylcysteine and ALF due to non-acetaminophen, viral infection, drug-induced or autoimmune hepatitis. The primary outcome was overall mortality. Secondary outcomes were transplant-free survival and length of hospital stay. Risk ratios were calculated using a random model for meta-analysis.
RESULTS
A total of 672 patients were included in this meta-analysis from 5 prospective studies (NAC group: = 334; control group: = 338). Viral hepatitis (45.8% vs. 32.8%) followed by drug-induced liver injury (24.6% vs. 27.5%), indeterminate cause (13.2% vs. 21.6%) and autoimmune hepatitis (6.6% vs. 8.9%) were the most common etiologies of ALF in the treatment group and control group respectively. Treatment with N-acetylcysteine improved the transplant-free survival significantly (55.1% vs. 28.1%; RR = 0.56; 95% CI: 0.33-0.94) whereas the overall survival was not improved with NAC (71% vs. 59.8%; RR = 0.73; 95% CI: 0.48-1.09). The NAC treatment was associated with shorter hospital stay (standard difference in means (SMD) = -1.62; 95% CI: -1.84 to -1.40, p < 0.001).
CONCLUSIONS
The treatment of patients with acute liver failure with N-acetylcysteine improved transplant-free survival and length of stay.
PubMed: 35371352
DOI: 10.5114/pg.2021.107797 -
The Cochrane Database of Systematic... Jan 2020Adolescent vaccination has received increased attention since the Global Vaccine Action Plan's call to extend the benefits of immunisation more equitably beyond... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adolescent vaccination has received increased attention since the Global Vaccine Action Plan's call to extend the benefits of immunisation more equitably beyond childhood. In recent years, many programmes have been launched to increase the uptake of different vaccines in adolescent populations; however, vaccination coverage among adolescents remains suboptimal. Therefore, understanding and evaluating the various interventions that can be used to improve adolescent vaccination is crucial.
OBJECTIVES
To evaluate the effects of interventions to improve vaccine uptake among adolescents.
SEARCH METHODS
In October 2018, we searched the following databases: CENTRAL, MEDLINE Ovid, Embase Ovid, and eight other databases. In addition, we searched two clinical trials platforms, electronic databases of grey literature, and reference lists of relevant articles. For related systematic reviews, we searched four databases. Furthermore, in May 2019, we performed a citation search of five other websites.
SELECTION CRITERIA
Randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series studies of adolescents (girls or boys aged 10 to 19 years) eligible for World Health Organization-recommended vaccines and their parents or healthcare providers.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened records, reviewed full-text articles to identify potentially eligible studies, extracted data, and assessed risk of bias, resolving discrepancies by consensus. For each included study, we calculated risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) where appropriate. We pooled study results using random-effects meta-analyses and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 16 studies (eight individually randomised trials, four cluster randomised trials, three non-randomised trials, and one controlled before-after study). Twelve studies were conducted in the USA, while there was one study each from: Australia, Sweden, Tanzania, and the UK. Ten studies had unclear or high risk of bias. We categorised interventions as recipient-oriented, provider-oriented, or health systems-oriented. The interventions targeted adolescent boys or girls or both (seven studies), parents (four studies), and providers (two studies). Five studies had mixed participants that included adolescents and parents, adolescents and healthcare providers, and parents and healthcare providers. The outcomes included uptake of human papillomavirus (HPV) (11 studies); hepatitis B (three studies); and tetanus-diphtheria-acellular-pertussis (Tdap), meningococcal, HPV, and influenza (three studies) vaccines among adolescents. Health education improves HPV vaccine uptake compared to usual practice (RR 1.43, 95% CI 1.16 to 1.76; I² = 0%; 3 studies, 1054 participants; high-certainty evidence). In addition, one large study provided evidence that a complex multi-component health education intervention probably results in little to no difference in hepatitis B vaccine uptake compared to simplified information leaflets on the vaccine (RR 0.98, 95% CI 0.97 to 0.99; 17,411 participants; moderate-certainty evidence). Financial incentives may improve HPV vaccine uptake compared to usual practice (RR 1.45, 95% CI 1.05 to 1.99; 1 study, 500 participants; low-certainty evidence). However, we are uncertain whether combining health education and financial incentives has an effect on hepatitis B vaccine uptake, compared to usual practice (RR 1.38, 95% CI 0.96 to 2.00; 1 study, 104 participants; very low certainty evidence). Mandatory vaccination probably leads to a large increase in hepatitis B vaccine uptake compared to usual practice (RR 3.92, 95% CI 3.65 to 4.20; 1 study, 6462 participants; moderate-certainty evidence). Provider prompts probably make little or no difference compared to usual practice, on completion of Tdap (OR 1.28, 95% CI 0.59 to 2.80; 2 studies, 3296 participants), meningococcal (OR 1.09, 95% CI 0.67 to 1.79; 2 studies, 3219 participants), HPV (OR 0.99, 95% CI 0.55 to 1.81; 2 studies, 859 participants), and influenza (OR 0.91, 95% CI 0.61 to 1.34; 2 studies, 1439 participants) vaccination schedules (moderate-certainty evidence). Provider education with performance feedback may increase the proportion of adolescents who are offered and accept HPV vaccination by clinicians, compared to usual practice. Compared to adolescents visiting non-participating clinicians (in the usual practice group), the adolescents visiting clinicians in the intervention group were more likely to receive the first dose of HPV during preventive visits (5.7 percentage points increase) and during acute visits (0.7 percentage points for the first and 5.6 percentage points for the second doses of HPV) (227 clinicians and more than 200,000 children; low-certainty evidence). A class-based school vaccination strategy probably leads to slightly higher HPV vaccine uptake than an age-based school vaccination strategy (RR 1.09, 95% CI 1.06 to 1.13; 1 study, 5537 participants; moderate-certainty evidence). A multi-component provider intervention (including an education session, repeated contacts, individualised feedback, and incentives) probably improves uptake of HPV vaccine compared to usual practice (moderate-certainty evidence). A multi-component intervention targeting providers and parents involving social marketing and health education may improve HPV vaccine uptake compared to usual practice (RR 1.41, 95% CI 1.25 to 1.59; 1 study, 25,869 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Various strategies have been evaluated to improve adolescent vaccination including health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. However, most of the evidence is of low to moderate certainty. This implies that while this research provides some indication of the likely effect of these interventions, the likelihood that the effects will be substantially different is high. Therefore, additional research is needed to further enhance adolescent immunisation strategies, especially in low- and middle-income countries where there are limited adolescent vaccination programmes. In addition, it is critical to understand the factors that influence hesitancy, acceptance, and demand for adolescent vaccination in different settings. This is the topic of an ongoing Cochrane qualitative evidence synthesis, which may help to explain why and how some interventions were more effective than others in increasing adolescent HPV vaccination coverage.
Topics: Adolescent; Child; Controlled Before-After Studies; Health Education; Health Personnel; Humans; Parents; Randomized Controlled Trials as Topic; Vaccination
PubMed: 31978259
DOI: 10.1002/14651858.CD011895.pub2 -
Journal of Hepatology Sep 2021Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS & AIMS
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
METHODS
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
RESULTS
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
CONCLUSIONS
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
LAY SUMMARY
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
Topics: Genome-Wide Association Study; Humans; Liver Cirrhosis, Biliary
PubMed: 34033851
DOI: 10.1016/j.jhep.2021.04.055 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
American Journal of Therapeutics Feb 2021Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic...
BACKGROUND
Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic transaminases, dizziness, neutropenia, and alopecia.
AREAS OF UNCERTAINTY
The main question of the systematic review is if albendazole administration can cause liver injury or liver failure.
DATA SOURCES
Two researchers conducted the search on PubMed and the key words used were: "albendazole," "anthelmintic," "drug-induced liver injury," and "acute hepatitis." Two new case reports were included in the systematic review.
RESULTS
Literature search concluded in 10 cases listed on PubMed. Another 2 new case reports from our experience are included in the systematic review. Most common symptoms presented are jaundice, anorexia, and vomiting after the single-use of albendazole or long-term usage. All cases presented high levels of transaminases, with remission after stopping the administration of albendazole. The treatment with albendazole was mostly given for liver hydatid cysts or empirically.
CONCLUSIONS
Albendazole is a prescription-based drug used by most patients without medical advice, without knowing the risk of side effects. The anthelmintic drug may induce liver injury, even in small doses; in result, practitioners and patients should take this information in consideration.
Topics: Albendazole; Anthelmintics; Chemical and Drug Induced Liver Injury, Chronic; Echinococcosis, Hepatic; Humans
PubMed: 33590990
DOI: 10.1097/MJT.0000000000001341 -
Food and Environmental Virology Sep 2023One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV... (Review)
Review
One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV in the Iberian Peninsula have been increasing through time with HEV infection being identified in humans and animals. The aim of the present systematic review was to compile and evaluate all the published data on HEV from studies performed in humans, animals and environmental samples in the Iberian Peninsula. The electronic databases Mendeley, PubMed, Scopus, and Web of Science were thoroughly searched, and research published up until February 01, 2023 were included. Resulting in a total of 151 eligible papers by full reading and application of PRISMA exclusion/inclusion criteria. Overall, the present review shows that several HEV genotypes, namely HEV-1, 3, 4, and 6 as well as Rocahepevirus, are circulating in humans, animals, and in the environment in the Iberian Peninsula. HEV-3 was the most common genotype circulating in humans in Portugal and Spain, as expected for developed countries, with HEV-1 only being detected in travelers and emigrants from HEV endemic regions. Spain is the biggest pork producer in Europe and given the high circulation of HEV in pigs, with HEV-3 being primarily associated to zoonotic transmission through consumption of swine meat and meat products, in our opinion, the introduction of an HEV surveillance system in swine and inclusion of HEV in diagnostic routines for acute and chronic human hepatitis would be important. Additionally, we propose that establishing a monitoring mechanism for HEV is crucial in order to gain a comprehensive understanding of the prevalence of this illness and the various strains present in the Iberian Peninsula, as well as their potential impact on public health.
Topics: Humans; Animals; Swine; Hepatitis E virus; Hepatitis E; Europe; Public Health; Meat; Genotype; Swine Diseases; Phylogeny
PubMed: 37434079
DOI: 10.1007/s12560-023-09560-5 -
Digestive Diseases and Sciences Jul 2021Infectious etiologies are rare cause of acute pancreatitis (AP). We sought to investigate the frequency of viral-attributed AP (VIAP) and describe its natural course and...
Infectious etiologies are rare cause of acute pancreatitis (AP). We sought to investigate the frequency of viral-attributed AP (VIAP) and describe its natural course and clinical features. Comprehensive review of PubMed and EMBASE in English until December 31, 2019, was performed. AP diagnosis and severity were defined per the Revised Atlanta Classification. Viral infections were diagnosed by serology and/or histology. A diagnosis of viral infection, with a concurrent AP diagnosis, a temporal resolution of both entities, and the attempt to exclude the most common etiologies of AP defined VIAP. Two independent reviewers reviewed eligible publications. Bias risk was assessed with the Murad tool. A total of 209 cases identified in 128 publications met inclusion criteria. Mean age was 38.9 ± 1.28 years. Male-to-female ratio was 2.2:1, and 28% of patients were immunocompromised. Viral hepatitis (A, B, C, D and E) was the most common virus and accounted for 34.4% of cases, followed by coxsackie and echoviruses (14.8%), hemorrhagic fever viruses (12.4%), CMV (12.0%), VZV (10.5%), mumps and measles (3.8%), primary HIV infection (3.8%), HSV (1.9%), EBV (1.9%), and the remainder of cases (2.9%) attributed to adenovirus, influenza H1N1, and multiple viruses. Severity of AP was: 43.1% mild, 11.7% moderately severe, 32.4% severe. Death occurred in 42 (20.1%) patients. A significant portion of VIAP patients were immunocompromised (28.0%) and accounted for 71.4% of mortality cases. Mortality was higher than that reported for AP from other etiologies in the literature.
Topics: Humans; Pancreatitis; Prognosis; Virus Diseases
PubMed: 32789532
DOI: 10.1007/s10620-020-06531-9 -
World Journal of Gastroenterology Dec 2022There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public...
BACKGROUND
There is growing evidence that patients with coronavirus disease 2019 (COVID-19) frequently present with liver impairment. Hepatitis B virus (HBV) remains a major public health threat in current society. Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV can cause liver damage, and current findings on whether HBV infection increases disease severity in COVID-19 patients are inconsistent, and whether SARS-CoV-2 infection accelerates hepatitis B progression or leads to a worse prognosis in hepatitis B patients has not been adequately elucidated.
AIM
To explore the complex relationship between COVID-19 and hepatitis B in order to inform the research and management of patients co-infected with SARS-CoV-2 and HBV.
METHODS
An experienced information specialist searched the literature in the following online databases: PubMed, China National Knowledge Infrastructure, Google Scholar, Scopus, Wiley, Web of Science, Cochrane, and ScienceDirect. The literature published from December 2019 to September 1, 2022 was included in the search. We also searched medRxiv and bioRxiv for gray literature and manually scanned references of included articles. Articles reporting studies conducted in humans discussing hepatitis B and COVID-19 were included. We excluded duplicate publications. News reports, reports, and other gray literature were included if they contained quantifiable evidence (case reports, findings, and qualitative analysis). Some topics that included HBV or COVID-19 samples but did not have quantitative evidence were excluded from the review.
RESULTS
A total of 57 studies were eligible and included in this review. They were from 11 countries, of which 33 (57.9%) were from China. Forty-two of the 57 studies reported abnormalities in liver enzymes, three mainly reported abnormalities in blood parameters, four indicated no significant liver function alterations, and another eight studies did not provide data on changes in liver function. Fifty-seven studies were retrospective and the total number of co-infections was 1932, the largest sample size was 7723, and the largest number of co-infections was 353. Most of the studies suggested an interaction between hepatitis B and COVID-19, while 12 studies clearly indicated no interaction between hepatitis B and COVID-19. Six of the 57 studies clearly reported HBV activation. Six studies were related to liver transplant patients.
CONCLUSION
There is some association between COVID-19 and hepatitis B. Future high-quality randomized trials are needed to further elucidate the interaction between COVID-19 and hepatitis B.
Topics: Humans; COVID-19; SARS-CoV-2; Coinfection; Retrospective Studies; Hepatitis B; Hepatitis B virus
PubMed: 36569273
DOI: 10.3748/wjg.v28.i46.6599 -
Phytomedicine : International Journal... Jan 2023The presence or absence of damage to the liver organ is crucial to a person's health. Nutritional disorders, alcohol consumption, and drug abuse are the main causes of... (Review)
Review
BACKGROUND
The presence or absence of damage to the liver organ is crucial to a person's health. Nutritional disorders, alcohol consumption, and drug abuse are the main causes of liver disease. Liver transplantation is the last irrevocable option for liver disease and has become a serious economic burden worldwide. Andrographolide (AP) is one of the main active ingredients of Herba Andrographitis. It has several biological activities and has been reported to have protective and therapeutic effects against liver diseases. Earlier literature has been written on AP's role in treating inflammation and other diseases, and there has not been a systematic review on liver diseases. This review is dedicated to sorting out the research results of AP against liver diseases. Pharmacokinetics, toxicity, and nanotechnology to improve bioavailability are discussed. Finally, an outlook and assessment of its future are provided.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and web of Science databases were used to search all relevant literature on AP for liver disease up to 2022.
RESULTS
Studies have shown that AP plays an important role in different liver disease phenotypes, mainly through anti-inflammatory and antioxidant activities. AP regulates HO-1 and inhibits hepatitis virus replication. It affects the NF-κB pathway, downregulates inflammatory factors such as IL-1β, IL-6, and TNF-α, and reduces liver damage. In preventing liver fibrosis, AP inhibits angiogenesis and activation of hepatic stellate cells and reduces oxidative stress involved in the Nrf2 and TGF-β1/Smad pathways. In addition, AP impedes the development of liver cancer by promoting apoptosis and autonomous phagocytosis in a cell-dependent way. Interestingly, miRNAs are involved in the therapeutic process of liver cancer and hepatic fibrosis. The poor solubility of AP limits the development of dosage forms. Therefore, the advent of nanoformulations has improved bioavailability. Although the effect of AP is dose- and time-dependent, the magnitude of its toxicity is not negligible. Some clinical trials have shown that AP has mild side effects.
CONCLUSIONS
AP, as an effective natural product, has a good effect on the liver disease through multiple pathways and targets. However, the dose reaches a certain level, leading to its toxicity and side effects. For better clinical application of AP, high-quality clinical and toxic intervention mechanisms are needed to validate current studies. In addition, modulation of miRNA-mediated hepatocellular carcinoma and liver fibrosis and synergistic action with drugs may be the future focus of AP. In conclusion, AP can be regarded as an important candidate for treating different liver diseases in the future.
Topics: Humans; Liver; Liver Cirrhosis; Diterpenes; NF-kappa B; Liver Neoplasms
PubMed: 36610122
DOI: 10.1016/j.phymed.2022.154537 -
Microbial Pathogenesis Feb 2020Mycoplasma pneumoniae (M. pneumoniae) is a small bacterium characterized by the absence of cell wall. It is a human pathogen causing upper and lower respiratory...
Mycoplasma pneumoniae (M. pneumoniae) is a small bacterium characterized by the absence of cell wall. It is a human pathogen causing upper and lower respiratory infections, both in adults and children. However, it is also considered to be implicated in the pathogenesis of several types of extra-respiratory diseases, including some gastrointestinal disorders. The liver involvement in children during or after M. pneumoniae infections is analyzed and discussed in this review. Through a systematic literature search, it is evidenced that M. pneumoniae is not infrequently associated with alteration of liver function, but rarely causes acute and severe hepatitis in children. M. pneumoniae should be considered as an unusual cause of acute hepatitis in children, whenever the most common hepatotropic viruses have been excluded. The pathogenesis of M. pneumoniae-related hepatitis is likely to be immune-mediated: both the innate and adaptive immune responses may play a fundamental role. However, the exact pathological mechanisms have to be elucidated yet. Further clinical studies are needed in order to understand the actual relevance of this microorganism in liver disease and its pathogenesis.
Topics: Acute Disease; Child; Databases, Factual; Gastrointestinal Diseases; Hepatitis; Humans; Liver; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 31712120
DOI: 10.1016/j.micpath.2019.103863