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JHEP Reports : Innovation in Hepatology Jun 2023Antivirals represent the mainstay of chronic hepatitis B treatment given their efficacy and tolerability, but rates of functional cure remain low during long-term...
BACKGROUND & AIMS
Antivirals represent the mainstay of chronic hepatitis B treatment given their efficacy and tolerability, but rates of functional cure remain low during long-term therapy. Treatment discontinuation has emerged as a strategy to maintain partial cure and achieve functional cure in select patient groups. We aimed to evaluate how data from treatment discontinuation studies exploring novel viral and/or immune markers could be applied to the functional cure program.
METHODS
Treatment discontinuation studies evaluating novel viral and/or immune markers were identified by a systematic search of the PubMed database through to October 30, 2022. Data extraction focused on information regarding novel markers, including identified cut-off levels, timing of measurement, and associated effect on study outcomes of virological relapse, clinical relapse, and HBsAg seroclearance.
RESULTS
From a search of 4,492 citations, 33 studies comprising a minimum of 2,986 unique patients met the inclusion criteria. Novel viral markers, HBcrAg and HBV RNA, were demonstrated across most studies to be helpful in predicting off-therapy partial cure, with emerging evidence to support a link with functional cure. From novel immune marker studies, we observed that treatment discontinuation has the potential to trigger immune restoration, which may be associated with a transient virological relapse. To this end, these studies support the combination of virus-directing agents with immunomodulator therapies to induce two key steps underlying functional cure: viral antigen load reduction and restoration of the host immune response.
CONCLUSIONS
Patients with a favourable profile of novel viral and immune markers stand to benefit from a trial of antiviral treatment discontinuation alongside novel virus-directing agents with the aim of achieving functional cure without excessive risk of severe clinical relapse.
IMPACT AND IMPLICATIONS
Select patients with chronic hepatitis B undergoing nucleoside analogue therapy may benefit from a trial of treatment discontinuation, aiming to maintain partial cure and/or achieve functional cure. We propose a profile of novel viral and immune markers to identify patients who are likely to achieve these goals without excessive risk of hepatic decompensation. Furthermore, treatment discontinuation may also be considered as a therapeutic strategy to trigger immune restoration, which may increase the chance of functional cure when used in conjunction with novel virus-directing agents.
PubMed: 37138673
DOI: 10.1016/j.jhepr.2023.100720 -
Virology Journal Jul 2021The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.
METHODS
We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis.
RESULTS
We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case-control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.
CONCLUSION
Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.
Topics: Computational Biology; Cross-Sectional Studies; Hepatitis C; Humans; Protein Interaction Maps; Psoriasis
PubMed: 34215260
DOI: 10.1186/s12985-021-01606-z -
Medical Sciences (Basel, Switzerland) Feb 2020Hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA icosahedral virus belongs to the genus within the Hepeviridae family. HEV infection can... (Review)
Review
Hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA icosahedral virus belongs to the genus within the Hepeviridae family. HEV infection can be asymptomatic, or it can cause icteric or fulminant hepatitis. Off late, there have been a number of publications reporting the extra-hepatic manifestations of HEV infection, and this systematic review is aimed at summarizing the available evidence in this regard. Two independent investigators searched PubMed, PubMed Central and Embase databases using the search string "(((hepatitis E) AND (Extrahepatic OR Extra-Hepatic))) OR ((Hepatitis E) AND (Neurology OR Cardiology OR Respiratory OR Lung OR Gastrointestinal OR musculoskeletal OR immunology OR pulmonary)) Filters: Abstract availability, English language, and Human studies". The extra-hepatic manifestations reported in each of the selected articles were classified and reported as neurological, cardiovascular, and hematological and miscellaneous manifestations. The total number of various manifestations reported in our study were = 324. These include neurological manifestations ( = 178/324 (54.94%)), cardiovascular and hematological manifestations ( = 113/324 (34.88%)), gastro-intestinal/pancreaticobiliary manifestations ( = 24/324 (7.41%)) and other rarer manifestations involving systems such as renal ( = 4/324; 1.24%), endocrine ( = 1/324; 0.31%), dermatology ( = 1/324; 0.31%), respiratory ( = 1/324; 0.31%), muscular ( = 1/324; 0.31%) and immune system ( = 1/324; 0.31%). Thus, HEV can have extra-hepatic manifestations affecting any system of the human body. Further research is needed to elucidate the underlying pathophysiological manifestations of these extra-hepatic manifestations and to prove causal association with HEV.
PubMed: 32033102
DOI: 10.3390/medsci8010009 -
Frontiers in Immunology 2021Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.
METHODS
A systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.
RESULTS
Eight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77-1.37; I = 30.9%, p = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52-1.06; I = 7.4%, p = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.
CONCLUSION
Viral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.
Topics: Animals; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Tumor Microenvironment
PubMed: 34659220
DOI: 10.3389/fimmu.2021.733530 -
Cureus Nov 2021Viral hepatitis is still considered a major cause of the burden of disease in India. It is the most common cause of cirrhosis and liver cancer. Prisoners are one of the... (Review)
Review
Viral hepatitis is still considered a major cause of the burden of disease in India. It is the most common cause of cirrhosis and liver cancer. Prisoners are one of the groups at most risk for hepatitis. This study aimed to estimate the pooled estimates of the prevalence of hepatitis B and C among prisoners in India. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study selection. The extensive search was done through databases of PubMed, Embase, and Google Scholar. All cross-sectional studies conducted to find the prevalence of hepatitis B and C among prison inmates in India published till June 2020 were screened and included in this meta-analysis. The analysis was conducted using the random-effects model. The heterogeneity was estimated using the I2 indicator. After extracting the required data, the meta-analysis was performed using the software Stata, version 12 (StataCorp LLC, College Station, Texas). The study is registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration no: CRD42020185137). Out of a total of 970 articles searched through the database of PubMed, Embase, and Google Scholar, five studies that met the inclusion criteria were included and analyzed. Hepatitis B and C prevalence were given in four studies each. The results showed that the overall prevalence of hepatitis B and C in prisoners was 8% (95% CI: 4-12) and 7% (95% CI: 1-13). The studies show high heterogeneity with no evidence of publication bias. The prevalence of hepatitis B and C among male prisoners was 4.48% (95% CI: 3.64%-5.32%) and 6.35% (95% CI: 5.48%-7.23%), respectively, while the prevalence among female prisoners was 1.53% (95% CI: 0.31-2.75) and 2.10% (95% CI: 0.28-3.93), respectively. The study findings show a high prevalence of hepatitis B and C in prisoners, which is of particular concern. Appropriate and effective interventions to reduce the transmission of hepatitis B and C in prisons are essential.
PubMed: 34956775
DOI: 10.7759/cureus.19672 -
BMC Public Health Jun 2023Hepatitis E virus (HEV) is the most common cause of acute hepatitis. While symptoms are generally mild and resolve within weeks, some populations (e.g., pregnant women,...
INTRODUCTION
Hepatitis E virus (HEV) is the most common cause of acute hepatitis. While symptoms are generally mild and resolve within weeks, some populations (e.g., pregnant women, immunocompromised adults) are at high-risk of severe HEV-related morbidity and mortality. There has not been a recent comprehensive review of contemporary HEV outbreaks, which limits the validity of current disease burden estimates. Therefore, we aimed to characterize global HEV outbreaks and describe data gaps to inform HEV outbreak prevention and response initiatives.
METHODS
We performed a systematic review of peer-reviewed (PubMed, Embase) and gray literature (ProMED) to identify reports of outbreaks published between 2011 and 2022. We included (1) reports with ≥ 5 cases of HEV, and/or (2) reports with 1.5 times the baseline incidence of HEV in a specific population, and (3) all reports with suspected (e.g., clinical case definition) or confirmed (e.g., ELISA or PCR test) cases if they met criterium 1 and/or 2. We describe key outbreak epidemiological, prevention and response characteristics and major data gaps.
RESULTS
We identified 907 records from PubMed, 468 from Embase, and 247 from ProMED. We screened 1,362 potentially relevant records after deduplication. Seventy-one reports were synthesized, representing 44 HEV outbreaks in 19 countries. The populations at risk, case fatalities, and outbreak durations were not reported in 66% of outbreak reports. No reports described using HEV vaccines. Reported intervention efforts included improving sanitation and hygiene, contact tracing/case surveillance, chlorinating boreholes, and advising residents to boil water. Commonly missing data elements included specific case definitions used, testing strategy and methods, seroprevalence, impacts of interventions, and outbreak response costs. Approximately 20% of HEV outbreaks we found were not published in the peer-reviewed literature.
CONCLUSION
HEV represents a significant public health problem. Unfortunately, extensive data shortages and a lack of standardized reporting make it difficult to estimate the HEV disease burden accurately and to implement effective prevention and response activities. Our study has identified major gaps to guide future studies and outbreak reporting systems. Our results support the development of standardized reporting procedures/platforms for HEV outbreaks to ensure accurate and timely data distribution, including active and passive coordinated surveillance systems, particularly among high-risk populations.
Topics: Pregnancy; Adult; Female; Humans; Hepatitis E; Seroepidemiologic Studies; Hepatitis E virus; Disease Outbreaks; Public Health
PubMed: 37308896
DOI: 10.1186/s12889-023-15792-8 -
Hepatology (Baltimore, Md.) May 2024Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive.
APPROACH AND RESULTS
A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)].
CONCLUSIONS
The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.
Topics: Humans; Hepatitis Delta Virus; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B Surface Antigens; Liver Cirrhosis; Morbidity; RNA, Viral; Disease Progression; Hepatitis B virus
PubMed: 37870278
DOI: 10.1097/HEP.0000000000000642 -
The Science of the Total Environment Jun 2022Enteric viruses are of great importance in wastewater due to their high excretion from infected individuals, low removal in wastewater treatment processes, long-time... (Review)
Review
Enteric viruses are of great importance in wastewater due to their high excretion from infected individuals, low removal in wastewater treatment processes, long-time survival in the environment, and low infectious dose. Among the other viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance in wastewater systems has received particular attention as a result of the current COVID-19 epidemic. Viruses adhering to solid particles in wastewater treatment processes will end up as sewage sludge, and therefore insufficient sludge treatment may result in viral particles dissemination into the environment. Here, we review data on viruses' presence in sewage sludge, their detection and concentration methods, and information on human health issues associated with sewage sludge land application. We used combinations of the following keywords in the Scopus, Web of Science (WOS), and PubMed databases, which were published between 2010 and January 21th, 2022: sludge (sewage sludge, biosolids, sewage solids, wastewater solids) and virus (enteric virus, viral particles, viral contamination, SARS-CoV-2, coronavirus). The sources were searched twice, once with and then without the common enteric virus names (adenovirus, rotavirus, norovirus, enterovirus, hepatitis A virus). Studies suggest adenovirus and norovirus as the most prevalent enteric viruses in sewage sludge. Indeed, other viruses include rotavirus, hepatitis A virus, and enterovirus were frequently found in sewage sludge samples. Untreated biological sludge and thickened sludge showed more viral contamination level than digested sludge and the lowest prevalence of viruses was reported in lime stabilized sludge. The review reveals that land application of sewage sludge may pose viral infection risks to people due to accidently ingestion of sludge or intake of crops grown in biosolids amended soil. Moreover, contamination of groundwater and/or surface water may occur due to land application of sewage sludge.
Topics: Adenoviridae; Biosolids; COVID-19; Enterovirus; Humans; Norovirus; Rotavirus; SARS-CoV-2; Sewage; Viruses; Wastewater
PubMed: 35182626
DOI: 10.1016/j.scitotenv.2022.153886 -
Journal of Viral Hepatitis Mar 2021Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of... (Meta-Analysis)
Meta-Analysis
Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty-four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95-CI 72%-84%) after ribavirin treatment. Twenty-five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon-alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-alpha increases the risk of transplant rejection and should therefore be administered with great caution.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis E; Hepatitis E virus; Humans; Interferon-alpha; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 33301609
DOI: 10.1111/jvh.13456 -
Gastroenterology and Hepatology From... 2022The purpose of the current study is to analyze the potential association between viral hepatitis and the severity of COVID-19. (Review)
Review
AIM
The purpose of the current study is to analyze the potential association between viral hepatitis and the severity of COVID-19.
BACKGROUND
Coronavirus disease 2019 (COVID-19) is a worldwide concern that has created major issues with many aspects. It is important to identify the risk factors for severe outcomes of this disease. To date, no association between viral hepatitis and severe COVID-19 has not been established.
METHODS
Through November 5, 2020, the databases of PubMed, Google Scholar, and medRxiv were systematically searched using specific keywords related to the focus of the study. All articles published on COVID-19 and viral hepatitis were retrieved. The Mantel-Haenszel formula with random-effects models was used to obtain the risk ratio (RR) along with its 95% confidence intervals (CIs) for dichotomous variables. The two-tailed -value was set with a value ≤0.05 considered statistically significant. Restricted-maximum likelihood meta-regression was done for several variables, such as age, gender, hypertension, diabetes, and other liver disease.
RESULTS
Analysis results included a total of 16 studies with a total of 14,682 patients. Meta-analysis showed that viral hepatitis increases the risk of developing severe COVID-19 (RR 1.68 (95% CI 1.26 - 2.22), = 0.0003, = 21%, random-effect modeling). According to the meta-regression analysis, the association between viral hepatitis and severe COVID-19 was not influenced by age ( = 0.067), diabetes ( = 0.057), or other liver disease ( = 0.646).
CONCLUSION
An increase of severe COVID-19 risk is associated with viral hepatitis. To reduce the risk of COVID-19, patients with viral hepatitis should be monitored carefully.
PubMed: 35611257
DOI: No ID Found