Antiviral Therapy Research Articles

Chronic Hepatitis D Virus Infection and Its Treatment: A Narrative Review

More than 12 million individuals worldwide are chronically infected with the hepatitis D virus (HDV). HDV infection is the most severe form of viral hepatitis since it requires hepatitis B virus co-infection and accelerates progression to cirrhosis and hepatocellular carcinoma. Therefore, treatment modalities to slow the progression of the disease are essential but not yet available. In addition, no antiviral treatment to date has been shown to reliably eradicate HDV. Pegylated interferon (PEG-IFN) is the only universally used treatment to suppress HDV RNA replication and improve liver inflammation and fibrosis. This treatment can be completed in 12–18 months, but cure rates remain low, and success does not reliably increase with the addition of a nucleos(t)ide analog. PEG-IFN therapy is also limited by poor tolerability and multiple adverse effects, including neutropenia, thrombocytopenia, and neuropsychiatric symptoms. Newer antiviral therapies in development target unique aspects of HDV viral replication and show promising results in combination with PEG-IFN for long-term HDV RNA suppression. These newer antiviral therapies include buleviritide (which blocks HDV entry), lonafarnib (which prevents HDV assembly), and REP-2139 (which prevents HDV export). In this manuscript, we discuss the characteristics of HDV infection and review the new antiviral therapies approved for treatment and those under investigation.

Factors involved in gastroesophageal varix-related events in patients with hepatitisC virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitisC virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. We conducted a multicenter study using prospective data from 478 hepatitisC virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. The median age was 70years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p<0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p=0.120). Across 35.7months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p=0.001). In the multivariate analysis, high-risk varix (p<0.001), high baseline gamma-glutamyl transpeptidase levels (p<0.001), and virologic failure (p=0.004) were significantly involved in varix-related events. The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

Involvement of E3 Ubiquitin Ligases in Viral Infections of the Human Host.

Viral infections are one of the principal causes of global primary health crises, with increased rate of infection and mortality demonstrated by the newer progeny of viruses. Viral invasion of the host involves utilization of various cellular machinery. Ubiquitination is one of a few central regulatory systems used by viruses for establishment of the infections in the host. Members of the ubiquitination system are involved in carrying out proteasomal degradation or functional modification of proteins in numerous cellular processes. E3 ubiquitin ligases play a major role in this system through recognition and recruitment of protein substrates and catalyzing the transfer of ubiquitin to these substrates. The versatility of ubiquitin ligases frequently makes them useful tools for the viruses, for either utilizing or degrading other cellular machineries, for carrying out their multiplication or inactivating the defensive strategies of the host. Therefore, these ligases are important targets for aiming at major pathways causing viral protein degradation or functional modification of the infection process. In this review, we have discussed the role and mechanism of different types of ubiquitin ligases in the context of infections of mainly human viruses, highlighting the viral proteins directly interacting with the ligases. Knowledge about these direct interactions is central in understanding the ubiquitin-dependent processes. This comprehensive account may also be beneficial for pharmaceutical exploration of E3 ligase-based broad-spectrum antiviral treatment.

Human cellular restriction factors that target SARS-CoV-2 replication

Millions of people have died and a worldwide economic catastrophe has been brought on by the coronavirus disease 2019 (COVID-19) pandemic. Infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may presently be treated with less than 10 antiviral drugs such as Remdesivir. The need for medical intervention due to sickness has led to unprecedented research efforts to study the biology of coronaviruses. Additionally, there is a strong likelihood that coronaviruses will cause pandemics in the future. All viruses cannot replicate optimally due to host restriction factors. Given that they are genetically more stable than viral targets and may be shared by similar viruses, these antiviral host factors provide appealing targets for antiviral treatment. The identification of antiviral host factors that are a component of human innate immunity and that prevent the completion of the SARS-CoV-2 life cycle has been made possible by the deployment of several “omics” technologies. In this review, we provide an overview of the antiviral host factors that limit the replication of SARS-CoV-2 in this, which were mostly discovered using functional genetic and interactome screening. Important cellular mechanisms for the SARS-CoV-2 life cycle are covered. Finally, we highlight host restriction factors that could be targeted by clinically approved molecules and the induction of these factors as potential antiviral therapies for COVID-19.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

The Potential Effectiveness of an Ancient Chinese Herbal Formula Yupingfeng-San for Prevention of COVID-19: A Systematic Review

The COVID-19 has been spreading all over the world, and human health is at stake. Conventional medicine played an important role in the treatment and syndrome relief, while there is limited research evidence to support any prevention or antiviral treatment for COVID-19. YupingfengSan is a classic formula with the effect of replenishing qi, consolidating exterior, and arresting sweating. YupingfengSan has been widely used to treat various diseases in China and Southeast Asia for hundreds of years. Accumulating evidence suggests that YPFS has both immune-regulatory and anti-virus effects clinically, but leaving the mechanism elusive. In this paper, we reviewed the recent progress of YupingfengSan in immune-regulatory and anti-virus activities, including the effect on mucosal immunity, biological antagonism, macrophages, adaptive immunity, and NK cells. From this systematic review, we speculate that YPFS can play an effective role in the prevention of SARS-CoV-2, but further experimental studies are expected to investigate the specific mechanisms. This review suggests an alternative direction for the prevention of COVID-19.

Combating Emerging Respiratory Viruses: Lessons and Future Antiviral Strategies

Emerging viral diseases, including seasonal illnesses and pandemics, pose significant global public health risks. Respiratory viruses, particularly coronaviruses and influenza viruses, are associated with high morbidity and mortality, imposing substantial socioeconomic burdens. This review focuses on the current landscape of respiratory viruses, particularly influenza and SARS-CoV-2, and their antiviral treatments. It also discusses the potential for pandemics and the development of new antiviral vaccines and therapies, drawing lessons from past outbreaks to inform future strategies for managing viral threats.

Influenza A as a True Zoonotic Pathogen: Transmission through Reservoir Hosts

Influenza A virus (IAV) represents a considerable global health threat due to its rapid mutation rates and broad host range, facilitating cross-species transmission and enabling the virus to evade immune defenses. This review explores the molecular mechanisms underlying IAV's pathogenicity, focusing on its zoonotic potential through reservoir hosts, such as wild birds and swine. The virus's ability to undergo antigenic shift and drift allows it to continually adapt to new hosts and environments, posing challenges for control and treatment. Current antiviral therapies are limited by the emergence of resistant strains, underscoring the necessity for innovative vaccine development and treatment strategies. By examining IAV's molecular evolution, immune evasion tactics, and transmission dynamics, this review highlights the critical need for enhanced surveillance, improved therapeutic options, and international cooperation to mitigate future outbreaks. A deeper understanding of these processes is essential to inform public health efforts and combat the persistent threat of IAV.

Adapted Milwaukee protocol for rabies treatment in a Brazilian indigenous child: case report

BackgroundThis case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol.Case presentationThe patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus’s neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group.ConclusionThe findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

Vaccination against respiratory syncytial virus (RSV)-For the protection of infants and older adults

Respiratory syncytial virus (RSV) is afrequent cause of respiratory infections in all age groups. Infections in infants and older adults frequently result in severe disease and complications. There is no specific antiviral treatment against RSV. The characterization of the structure of the fusion (F) protein in its immunogenic prefusion conformation has enabled the development of novel vaccines directed against the prefusion protein as the antigen. These include an adjuvanted monovalent vaccine (Arexvy) and anonadjuvanted bivalent vaccine (Abrysvo). Both are approved and indicated for use in older adults, in whom they have been shown to be over 80% effective in the protection against symptomatic RSV infections and associated lower respiratory tract diseases. Abrysvo is approved for use in pregnancy to protect the newborn through the transplacental transfer of high-titer maternal antibodies. The vaccine has been shown to have an efficacy of over 80% in the first 3 months of life to protect the infant from severe RSV-associated lower respiratory disease but slightly deceases after an age of 6 months. The clinical studies demonstrated the safety of the vaccines in both adults and pregnant women. The rate of undesired side effects was low in all studies and severe side effects were very rare. The new vaccines are efficacious new tools to prevent RSV-associated disease and complications in high-risk groups. For infants, an alternative strategy can be passive immunization with monoclonal antibodies, including the recently developed nirsevimab, which has also shown high efficacy.

Changes in the expression profile of serum lncRNAs in pregnant women with high hepatitis B viral load during antiviral and non-antiviral treatment

ObjectiveThis research analyzes the potential of long non-coding RNAs (lncRNAs) as markers in determining the necessity of antiviral treatment in pregnant women by examining alterations in the expression profile of serum lncRNAs in pregnant women with elevated hepatitis B viral load (HBVL) under antiviral and non-antiviral treatment regimens between the second trimester and delivery.MethodsSerum was obtained from 6 s-trimester pregnant women with high HBVL and no intrauterine infection. Then, 3 of these women were randomly selected for antiviral treatment, with the remaining 3 women undergoing non-antiviral treatment as control. Serum samples were again collected from these 6 women before delivery. The expression profile of lncRNAs was analyzed with microarray technology, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The axes of hub lncRNA-miRNA-mRNA were identified based on the competing endogenous RNA (ceRNA) network.ResultsThe expression profile of serum lncRNAs in pregnant women with high HBVL changed significantly from the second trimester of pregnancy until delivery under antiviral or non-antiviral treatment. The Venn diagram was utilized to screen out the jointly up-regulated and down-regulated lncRNAs in the serum of pregnant women under antiviral and non-antiviral treatment before delivery. Additionally, the KEGG pathway enrichment analysis results showed that lncRNAs might mediate the Hippo pathway in HBV infection. Based on the ceRNA network, 3 hub lncRNAs (CATG00000076041.1, LINC01310, and G014655) were found to potentially regulate the key gene TP73 in the Hippo pathway.ConclusionIn this study, we retrieved co-differentially expressed lncRNAs in pregnant women with high HBVL under antiviral or non-antiviral treatment, which may be used as markers for evaluating whether pregnant women with high HBVL may be free of antiviral treatment. This study may provide a basis for preventing potential adverse effects of antiviral treatment on maternal and fetal health.

Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C

Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C

Viral Infections and the Glutathione Peroxidase Family: Mechanisms of Disease Development.

Significance: The glutathione peroxidase (GPx) family is recognized for its essential function in maintaining cellular redox balance and countering the overproduction of reactive oxygen species (ROS), a process intricately linked to the progression of various diseases including those spurred by viral infections. The modulation of GPx activity by viruses presents a critical juncture in disease pathogenesis, influencing cellular responses and the trajectory of infection-induced diseases. Recent Advances: Cutting-edge research has unveiled the GPx family's dynamic role in modulating viral pathogenesis. Notably, GPX4's pivotal function in regulating ferroptosis presents a novel avenue for the antiviral therapy. The discovery that selenium, an essential micronutrient for GPx activity, possesses antiviral properties has propelled us toward rethinking traditional treatment modalities. Critical Issues: Deciphering the intricate relationship between viral infections and GPx family members is paramount. Viral invasion can precipitate significant alterations in GPx function, influencing disease outcomes. The multifaceted nature of GPx activity during viral infections suggests that a deeper understanding of these interactions could yield novel insights into disease mechanisms, diagnostics, prognostics, and even chemotherapeutic resistance. Future Directions: This review aims to synthesize current knowledge on the impact of viral infections on GPx activity and expression and identify key advances. By elucidating the mechanisms through which GPx family members intersect with viral pathogenesis, we propose to uncover innovative therapeutic strategies that leverage the antioxidant properties of GPx to combat viral infections. The exploration of GPx as a therapeutic target and biomarker holds promise for the development of next-generation antiviral therapies. Antioxid. Redox Signal. 00, 000-000.

The structure of lipopeptides impacts their antiviral activity and mode of action against SARS-CoV-2 in vitro.

This study advances our understanding of how lipopeptides, which are molecules mostly produced by bacteria, with both fat and protein components, can be used to fight viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By analyzing 15 different lipopeptides, researchers identified key structural features that make some of these molecules particularly effective at reducing viral levels while being less harmful to cells. Specifically, lipopeptides with certain charged amino acids were found to have the strongest antiviral effects. This research lays the groundwork for developing new antiviral treatments that are both potent against viruses and safe for human cells, offering hope for better therapeutic options in the future.

Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients.

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients. Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies. Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

Elevated intestinal fatty acid-binding protein levels as a marker of portal hypertension and gastroesophageal varices in cirrhosis

We measured intestinal fatty acid-binding protein (I-FABP) levels, a useful marker of small intestinal mucosal injury, in patients with cirrhosis to determine their relationship with liver function and complications. This cross-sectional study included 71 patients with cirrhosis admitted for treatment of cirrhotic complications or hepatocellular carcinoma (cohort A) and 104 patients with cirrhosis who received direct-acting antiviral therapy for HCV (cohort B). I-FABP levels, measured by ELISA, were evaluated relative to hepatic reserve and compared with non-invasive scoring systems for diagnostic performance in cirrhotic complications. The median I-FABP level in both cohorts were significantly elevated in patients with reduced hepatic reserve (CTP grade A/BC cohort A, 2.33/3.17 ng/mL, p = 0.032; cohort B, 2.46/3.64 ng/mL, p = 0.008) and complications with gastroesophageal varices (GEV; GEV (-)/(+) cohort A, 1.66/3.67 ng/mL, p < 0.001; cohort B, 2.32/3.36 ng/mL; p = 0.003). Further, multiple logistic regression analysis identified I-FABP as the only factor contributing to GEV presence in both cohorts, which outperformed non-invasive scoring systems for GEV diagnosis (sensitivity 84.6%; specificity 84.2%; sensitivity 69.6%; specificity 63.8%, respectively). In conclusion, elevated small-intestinal mucosal injury in patients with cirrhosis was related to reduced hepatic reserve and GEV presence. I-FABP levels reflect portal hypertension and may be useful in cirrhosis management.

Foscarnet eyedrops for the treatment of refractory herpetic keratitis

PurposeThe purpose of this case series is to describe the clinical course of patients receiving foscarnet eyedrops for the treatment of refractory herpetic keratitis.ObservationsSix patients diagnosed with herpetic keratitis were treated with foscarnet 24 mg/mL (2.4%) eyedrops with resulting improvement in keratitis.ConclusionTopical foscarnet may be a safe and effective treatment for herpetic keratitis in conjunction with, or as an alternative to, conventional antiviral therapy. This is an off-label use of foscarnet.

The role of artificial intelligence in the management of liver diseases.

Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.