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International Journal of Molecular... Jun 2022Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis globally, which can occasionally lead to acute liver failure (ALF) and acute-on-chronic liver...
Hepatitis A virus (HAV) infection is a major cause of acute viral hepatitis globally, which can occasionally lead to acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), which often result in death without liver transplantation [...].
Topics: Acute-On-Chronic Liver Failure; Hepatitis A; Hepatitis A virus; Hepatitis, Viral, Human; Humans; Liver Transplantation
PubMed: 35806219
DOI: 10.3390/ijms23137214 -
World Journal of Gastroenterology Feb 2022Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and... (Review)
Review
Viral hepatitis is a significant health problem worldwide, associated with morbidity and mortality. Hepatitis B, C, D, and occasionally E viruses (HBV, HCV, HDV, and HEV) can evolve in chronic infections, whereas hepatitis A virus (HAV) frequently produces acute self-limiting hepatitis. In the last years, different studies have been performed to introduce new antiviral therapies. The most important goal in the treatment of viral hepatitis is to avoid chronic liver disease and complications. This review analyzes currently available therapies, in particular for viruses associated with chronic liver disease. The focus is especially on HBV and HCV therapies, investigating new drugs already introduced in clinical practice and clinical trials. We also describe new entry inhibitors, developed for the treatment of chronic HDV and HBV and currently available treatments for HEV. The last drugs introduced have shown important efficacy in HCV, with achievable target HCV elimination by 2030. Concurrently, renewed interest in curative HBV therapies has been registered; current nucleotide/nucleoside analogs positively impact liver-related complications, ensuring high safety and tolerability. Novel approaches to HBV cure are based on new antivirals, targeting different steps of the HBV life cycle and immune modulators. The improved knowledge of the HDV life cycle has facilitated the development of some direct-acting agents, as bulevirtide, the first drug conditionally approved in Europe for HDV associated compensated liver disease. Further studies are required to identify a new therapeutic approach in hepatitis E, especially in immunosuppressed patients.
Topics: Hepatitis B; Hepatitis B virus; Hepatitis, Viral, Human; Humans; Lipopeptides; Motivation
PubMed: 35316960
DOI: 10.3748/wjg.v28.i5.517 -
Current Opinion in Gastroenterology May 2023Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20... (Review)
Review
PURPOSE OF REVIEW
Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20 million people are infected with HEV annually, yet the epidemiology, diagnosis and prevention remain elusive in many clinical settings.
RECENT FINDINGS
Orthohepevirus A (HEV-A) genotypes 1 and 2 cause acute, self-limited hepatitis through faecal-oral transmission. In 2022, the first-ever vaccine campaign was implemented as a response to an HEV outbreak in an endemic region. HEV-A genotypes 3 and 4 are zoonotic infections that primarily cause chronic HEV infection in immunosuppressed populations. Pregnant women and immunocompromised persons are at high risk for severe illness in some settings. Another recent advance in our knowledge of HEV is the zoonotic transmission of Orthohepevirus C (HEV-C) to humans, presumably from contact with rodents and/or their excrement. Previously, HEV infection in humans was presumed to be limited to HEV-A only.
SUMMARY
Clinical recognition and accurate diagnosis are essential to the management of HEV infection and understanding the global burden of the disease. Epidemiology affects clinical presentations. Targeted response strategies in HEV outbreaks are needed for the prevention of disease, and vaccine campaigns may prove to be an effective part of these strategies.
Topics: Animals; Humans; Female; Pregnancy; Hepatitis E virus; Hepatitis E; Zoonoses; Disease Outbreaks; Acute Disease
PubMed: 36976855
DOI: 10.1097/MOG.0000000000000918 -
Gut Oct 2023Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion,...
OBJECTIVE
Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction.
DESIGN
Metabolic state, exhaustion and transcriptome of virus-specific CD8 T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52 were determined and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested . Intrahepatic virus-specific CD8 T cells were analysed by scRNA-Seq in a HBV-replicating murine model of acute and chronic infection.
RESULTS
HBV-specific (core, polymerase) and HCV-specific (NS3, NS3, NS5B) CD8 T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase -specific CD8 T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8 T cells in a murine model of chronic infection.
CONCLUSION
Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.
Topics: Humans; Animals; Mice; CD8-Positive T-Lymphocytes; Antiviral Agents; Persistent Infection; Hepatitis C, Chronic; Hepatitis B, Chronic; Hepatitis C; Hepatitis Viruses; Hepatitis B virus
PubMed: 37541771
DOI: 10.1136/gutjnl-2022-328734 -
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 Family Physician Apr 2022Alcoholic hepatitis is a clinical syndrome characterized by acute-onset jaundice and liver enzyme abnormalities in the setting of long-term heavy alcohol use. High rates...
Alcoholic hepatitis is a clinical syndrome characterized by acute-onset jaundice and liver enzyme abnormalities in the setting of long-term heavy alcohol use. High rates of concomitant infections, systemic inflammation, and multiorgan failure lead to significant morbidity and mortality. Diagnosis of alcoholic hepatitis is primarily clinical, based on a consensus definition from the National Institute on Alcohol Abuse and Alcoholism. Initial workup should include chest radiography and cultures of peritoneal fluid, blood, and urine. Close monitoring for inflammation and organ failure is crucial throughout hospitalization. Laboratory-based prognostic scores, including Maddrey Discriminant Function and the Model for End-Stage Liver Disease, help determine disease severity and treatment options. Treatment for moderate disease primarily consists of supportive care, including alcohol cessation and nutritional support. Corticosteroids are recommended for severe alcoholic hepatitis. Responsiveness to corticosteroid therapy should be evaluated using the Lille score on day 7 of treatment. Hospital physicians should involve a multidisciplinary team, including substance abuse specialists, gastroenterologists or hepatologists, nephrologists, dietitians, and intensivists, as appropriate. Long-term follow-up should focus on abstinence from alcohol, management of underlying cirrhosis, and evaluation for liver transplantation if indicated. Pharmacologic treatment of alcohol use disorder can aid patients in maintaining abstinence from alcohol. The presence of underlying cirrhosis and continued alcohol use negatively impact long-term prognosis.
Topics: End Stage Liver Disease; Hepatitis, Alcoholic; Humans; Inflammation; Liver Cirrhosis; Severity of Illness Index
PubMed: 35426628
DOI: No ID Found -
Ugeskrift For Laeger Feb 2021Hepatotoxicity is a well-known side effect to isoniazid treatment with the risk of progression to liver failure. This case report describes a 39-year-old male, who...
Hepatotoxicity is a well-known side effect to isoniazid treatment with the risk of progression to liver failure. This case report describes a 39-year-old male, who received standard isoniazid treatment for latent TB infection (LTBI) and developed severe isoniazid-induced acute hepatitis. Liver transplantation was considered, but the patient slowly recovered with full hepatic regeneration. With increasing focus on treating LTBI in Denmark, routine follow-up including biochemical monitoring should be implemented for patients receiving LTBI treatment to prevent severe complications.
Topics: Adult; Antitubercular Agents; Hepatitis; Humans; Isoniazid; Latent Tuberculosis; Male
PubMed: 33570026
DOI: No ID Found -
Journal of Hepatology Jul 2021Interleukin (IL)-20 and IL-22 belong to the IL-10 family. IL-10 is a well-documented anti-inflammatory cytokine while IL-22 is well known for epithelial protection and...
BACKGROUND & AIMS
Interleukin (IL)-20 and IL-22 belong to the IL-10 family. IL-10 is a well-documented anti-inflammatory cytokine while IL-22 is well known for epithelial protection and its antibacterial function, showing great therapeutic potential for organ damage; however, the function of IL-20 remains largely unknown.
METHODS
Il20 knockout (Il20) mice and wild-type littermates were generated and injected with Concanavalin A (ConA) and Klebsiella pneumoniae (K.P.) to induce acute hepatitis and bacterial infection, respectively.
RESULTS
Il20 mice were resistant to acute hepatitis and exhibited selectively elevated levels of the hepatoprotective cytokine IL-6. Such selective inhibition of IL-6 by IL-20 was due to IL-20 targeting hepatocytes that produce high levels of IL-6 but a limited number of other cytokines. Mechanistically, IL-20 upregulated NAD(P)H: quinone oxidoreductase 1 (NQO1) expression and subsequently promoted the protein degradation of transcription factor IκBζ, resulting in selective downregulation of the IκBζ-dependent gene Il6 as well several other IκBζ-dependent genes including lipocalin-2 (Lcn2). Given the important role of IL-6 and LCN2 in limiting bacterial infection, we examined the effect of IL-20 on bacterial infection and found Il20 mice were resistant to K.P. infection and exhibited elevated levels of hepatic IκBζ-dependent antibacterial genes. Moreover, IL-20 upregulated hepatic NQO1 by binding to IL-22R1/IL-20R2 and activating ERK/p38MAPK/NRF2 signaling pathways. Finally, the levels of hepatic IL1B, IL20, and IκBζ target genes were elevated, and correlated with each other, in patients with severe alcoholic hepatitis.
CONCLUSIONS
IL-20 selectively inhibits hepatic IL-6 production rather than exerting IL-10-like broad anti-inflammatory properties. Unlike IL-22, IL-20 aggravates acute hepatitis and bacterial infection. Thus, anti-IL-20 therapy could be a promising option to control acute hepatitis and bacterial infection.
LAY SUMMARY
Several interleukin (IL)-20 family cytokines have been shown to play important roles in controllimg inflammatory responses, infection and tissue damage, but the role of IL-20 remains unclear. Herein, we elucidated the role of IL-20 in liver disease and bacterial infection. We show that IL-20 can aggravate hepatitis and bacterial infection; thus, targeting IL-20 holds promise for the treatment of patients with liver disease.
Topics: Adaptor Proteins, Signal Transducing; Animals; Bacterial Infections; Drug Discovery; Gene Expression Regulation; Hepatitis; Hepatitis, Alcoholic; Humans; Interleukin-1beta; Interleukins; Liver; Mice; Mice, Knockout; NAD(P)H Dehydrogenase (Quinone); Proteolysis; Up-Regulation
PubMed: 33610678
DOI: 10.1016/j.jhep.2021.02.004 -
Journal of Hepatology Sep 2021Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating...
BACKGROUND & AIMS
Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention.
METHODS
Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described.
RESULTS
In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH.
CONCLUSIONS
The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH.
LAY SUMMARY
We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.
Topics: Developing Countries; Disability-Adjusted Life Years; Global Burden of Disease; Hepatitis, Viral, Human; Humans; Incidence; Quality-Adjusted Life Years; Social Class
PubMed: 33961940
DOI: 10.1016/j.jhep.2021.04.035 -
Viruses Jan 2023The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant... (Review)
Review
The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant lymphoma. Currently, direct-acting antiviral agents (DAAs) against HCV infection can lead to a sustained virological response (SVR) in almost all HCV-infected patients. In this review article, we discuss acute exacerbation and alanine aminotransferase (ALT) flare in patients with chronic HCV infection. Although acute liver failure caused by HCV infection is rare, careful attention should be paid to the cases with ALT elevation during the natural course of chronic HCV infection. HCV genotype 2 infection, the use of rituximab, and a higher dose of corticosteroid are factors associated with HCV acute exacerbation and ALT flare. Treatment regimens for cancer have been interrupted or changed due to ALT flare due to HCV infection in some patients undergoing chemotherapy for cancer. The pathogenesis of HCV acute exacerbation and ALT flare could involve cellular as well as humoral immune responses. In the DAA era, the earlier introduction of DAAs may prevent chronic HCV-infected patients with acute exacerbation and ALT flare from developing into a more severe form, although DAAs may not be effective for all of them.
Topics: Humans; Hepatitis C, Chronic; Antiviral Agents; Alanine Transaminase; Hepatitis C; Hepacivirus; Liver Neoplasms
PubMed: 36680223
DOI: 10.3390/v15010183