Chiara Romano
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Chiara Romano has a total of 50 co-authors. Here are the top co-authors by number of shared publications:
- Massimo Ciccozzi
Unit of Medical Statistics and Molecular Epidemiology Università Campus Bio‐Medico di Roma Rome Italy
13 shared publications - Francesco Branda
Unit of Medical Statistics and Molecular Epidemiology Università Campus Bio‐Medico di Roma Rome Italy
12 shared publications - Fabio Scarpa
University of Sassari
11 shared publications - Daria Sanna
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100 Sassari, Italy
10 shared publications - Giancarlo Ceccarelli
Department of Public Health and Infectious Diseases, University Hospital Policlinico Umberto I Sapienza University of Rome Rome Italy
10 shared publications - Marco Casu
Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy
10 shared publications
Latest Publications
- Open Access
Modelling serological multiplex bead assays responses: A case study from Malaysia
Background: Multiplex bead assays (MBAs) provide quantitative measurements of many analytes from small sample volumes, reducing cost and processing time compared with traditional immunoassays. These advantages have made MBAs valuable for studying diverse diseases, particularly in low-resource settings. However, most analytical approaches focus on individual diseases, while integrated surveillance platforms would benefit from methods that jointly analyse the full range of pathogens included in multiplex assays. Methods: We applied factor analysis combined with a Dirichlet process mixture model to identify sub-populations based on MBA responses and assess whether these groups show spatial patterns or share socioeconomic characteristics and disease exposures. Data were drawn from four districts in northern Sabah, Malaysia, and included antibody responses for several neglected tropical diseases (NTDs): strongyloidiasis, lymphatic filariasis, giardiasis, toxoplasmosis, trachoma, and yaws. Results: The model identified four distinct sub-populations. Three of these were spatially distributed and included people with similar socioeconomic profiles. These shared characteristics may help explain the antibody patterns observed within each group, offering a comprehensive characterization of each sub-population. Conclusion: This methodology replicable to other MBA datasets and can provide new insights into the interplay of various exposures at the population level. It also has potential to strengthen integrated surveillance systems by informing more targeted sampling strategies.
Open AccessModelling serological multiplex bead assays responses: A case study from Malaysia
Background: Multiplex bead assays (MBAs) provide quantitative measurements of many analytes from small sample volumes, reducing cost and processing time compared with traditional immunoassays. These advantages have made MBAs valuable for studying diverse diseases, particularly in low-resource settings. However, most analytical approaches focus on individual diseases, while integrated surveillance platforms would benefit from methods that jointly analyse the full range of pathogens included in multiplex assays. Methods: We applied factor analysis combined with a Dirichlet process mixture model to identify sub-populations based on MBA responses and assess whether these groups show spatial patterns or share socioeconomic characteristics and disease exposures. Data were drawn from four districts in northern Sabah, Malaysia, and included antibody responses for several neglected tropical diseases (NTDs): strongyloidiasis, lymphatic filariasis, giardiasis, toxoplasmosis, trachoma, and yaws. Results: The model identified four distinct sub-populations. Three of these were spatially distributed and included people with similar socioeconomic profiles. These shared characteristics may help explain the antibody patterns observed within each group, offering a comprehensive characterization of each sub-population. Conclusion: This methodology replicable to other MBA datasets and can provide new insights into the interplay of various exposures at the population level. It also has potential to strengthen integrated surveillance systems by informing more targeted sampling strategies.
- Open Access
RETRACTED: Branda et al. Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World. Viruses 2024, 16, 1688
The journal retracts the article “Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World”
Open AccessRETRACTED: Branda et al. Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World. Viruses 2024, 16, 1688
The journal retracts the article “Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World”
- Top Cited PapersOpen Access
Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges
Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions.
Top Cited PapersOpen AccessHuman T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges
Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions.
- Open Access
- 24 January 2025
- Published by MDPI AG in Microorganisms
- Vol. 13 (2) , 253
SARS-CoV-2 XEC: A Genome-Based Survey
Recombination, a process of genetic exchange between distinct organisms, has played a critical role in the emergence of SARS-CoV-2 variants such as the XEC recombinant. This study provides a detailed genomic and structural characterization of XEC, derived from the recombination of lineages KP.3.3 (donor) and KS.1.1 (acceptor). Phylogenomic analyses reveal that XEC and its descendant XEC.1 form a monophyletic clade with close evolutionary ties to KP.3.3. The genomic breakpoint, spanning nucleotide positions 22,363–22,463, marks the shift from KS.1.1 to KP.3.3 within the spike protein gene. Mutational analysis highlights shared traits with its parental lineages, including mutations associated with immune evasion, receptor affinity, and fusogenicity. Notable changes, such as Q493E and L455S, may confer unique immunogenic properties, though XEC’s overall immune escape potential is limited by the absence of new mutations in conserved epitopes. Despite these mutations, XEC demonstrates restricted geographical spread, low genetic variability, and an evolutionary trajectory indicative of an evolutionary dead-end. Bayesian Skyline Plot analysis corroborates this, showing stable but declining population size. These findings underscore the need for ongoing genomic surveillance to monitor recombinant variants’ characteristics and public health impact. This study contributes to understanding viral evolution and highlights the importance of distinguishing variants of concern from those with minimal epidemiological significance.
- 24 January 2025
- Published by MDPI AG in Microorganisms
- Vol. 13 (2) , 253
Open AccessSARS-CoV-2 XEC: A Genome-Based Survey
Recombination, a process of genetic exchange between distinct organisms, has played a critical role in the emergence of SARS-CoV-2 variants such as the XEC recombinant. This study provides a detailed genomic and structural characterization of XEC, derived from the recombination of lineages KP.3.3 (donor) and KS.1.1 (acceptor). Phylogenomic analyses reveal that XEC and its descendant XEC.1 form a monophyletic clade with close evolutionary ties to KP.3.3. The genomic breakpoint, spanning nucleotide positions 22,363–22,463, marks the shift from KS.1.1 to KP.3.3 within the spike protein gene. Mutational analysis highlights shared traits with its parental lineages, including mutations associated with immune evasion, receptor affinity, and fusogenicity. Notable changes, such as Q493E and L455S, may confer unique immunogenic properties, though XEC’s overall immune escape potential is limited by the absence of new mutations in conserved epitopes. Despite these mutations, XEC demonstrates restricted geographical spread, low genetic variability, and an evolutionary trajectory indicative of an evolutionary dead-end. Bayesian Skyline Plot analysis corroborates this, showing stable but declining population size. These findings underscore the need for ongoing genomic surveillance to monitor recombinant variants’ characteristics and public health impact. This study contributes to understanding viral evolution and highlights the importance of distinguishing variants of concern from those with minimal epidemiological significance.
- Open Access
- 20 January 2025
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 14 (2) , 639
Retrospective Analysis of R-COMP Therapy in Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Assessing the Impact of Sample Selection Bias
Background: Retrospective studies are often criticized for their susceptibility to case selection bias compared to prospective studies, which include all patients consecutively and are thus less prone to such limitations. However, the larger sample sizes typical of retrospective studies can sometimes offset this drawback. On behalf of the Fondazione Italiana Linfomi (FIL), a substantial retrospective study involving 946 patients was conducted to examine the use of non-pegylated liposomal anthracycline (Myocet). This was followed by a prospective study, the Prospective Elderly Project, which enrolled 308 patients treated with the same liposomal anthracycline regimen. Methods: The objective of this analysis was to determine whether the patient cohort from the retrospective study significantly differed from the cohort in the prospective study. Statistical hypothesis testing was applied to assess whether the samples from both studies originated from the same underlying population. The Anderson–Darling test, a non-parametric statistical method, was utilized to evaluate and compare the overall survival distributions between the two patient cohorts. Results: The statistical tests produced conflicting results, suggesting a potential selection bias in the retrospective study or the possibility that the two groups were from the same population. These discrepancies may have arisen due to the choice of statistical methods or the quality of the data analyzed. Conclusions: This study highlights the challenges of comparing retrospective and prospective cohorts and underscores the importance of selecting appropriate statistical methodologies. The findings provide valuable insights and lay the groundwork for developing innovative approaches to improve such comparisons in future research.
- 20 January 2025
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 14 (2) , 639
Open AccessRetrospective Analysis of R-COMP Therapy in Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Assessing the Impact of Sample Selection Bias
Background: Retrospective studies are often criticized for their susceptibility to case selection bias compared to prospective studies, which include all patients consecutively and are thus less prone to such limitations. However, the larger sample sizes typical of retrospective studies can sometimes offset this drawback. On behalf of the Fondazione Italiana Linfomi (FIL), a substantial retrospective study involving 946 patients was conducted to examine the use of non-pegylated liposomal anthracycline (Myocet). This was followed by a prospective study, the Prospective Elderly Project, which enrolled 308 patients treated with the same liposomal anthracycline regimen. Methods: The objective of this analysis was to determine whether the patient cohort from the retrospective study significantly differed from the cohort in the prospective study. Statistical hypothesis testing was applied to assess whether the samples from both studies originated from the same underlying population. The Anderson–Darling test, a non-parametric statistical method, was utilized to evaluate and compare the overall survival distributions between the two patient cohorts. Results: The statistical tests produced conflicting results, suggesting a potential selection bias in the retrospective study or the possibility that the two groups were from the same population. These discrepancies may have arisen due to the choice of statistical methods or the quality of the data analyzed. Conclusions: This study highlights the challenges of comparing retrospective and prospective cohorts and underscores the importance of selecting appropriate statistical methodologies. The findings provide valuable insights and lay the groundwork for developing innovative approaches to improve such comparisons in future research.
- Open Access
- 18 December 2024
- Published by Springer Nature in Scientific Data
- Vol. 11 (1) , 1-8
Monitoring measles infections using flight passenger dynamics in Europe: A data-driven approach
This paper presents an open-access repository collecting information on measles virus infections and flight passenger movements in European countries from 2011 to 2023. It provides a comprehensive overview of reported measles cases and measles-mumps-rubella (MMR) vaccination coverage from authoritative organizations such as the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC). In addition, the dataset includes detailed data on passenger movements between countries, facilitating analysis of cross-border disease transmission. This resource enables more precise spatial analyses for monitoring and forecasting measles outbreaks, underscoring the importance of adequate vaccination coverage and sustained international surveillance to prevent the spread of the disease.
- 18 December 2024
- Published by Springer Nature in Scientific Data
- Vol. 11 (1) , 1-8
Open AccessMonitoring measles infections using flight passenger dynamics in Europe: A data-driven approach
This paper presents an open-access repository collecting information on measles virus infections and flight passenger movements in European countries from 2011 to 2023. It provides a comprehensive overview of reported measles cases and measles-mumps-rubella (MMR) vaccination coverage from authoritative organizations such as the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC). In addition, the dataset includes detailed data on passenger movements between countries, facilitating analysis of cross-border disease transmission. This resource enables more precise spatial analyses for monitoring and forecasting measles outbreaks, underscoring the importance of adequate vaccination coverage and sustained international surveillance to prevent the spread of the disease.
- Open Access
Human Papillomavirus (HPV) Vaccination: Progress, Challenges, and Future Directions in Global Immunization Strategies
Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the efficacy of these vaccines, global immunization efforts still face several obstacles, including low vaccination coverage in low- and middle-income countries, vaccine hesitancy, and disparities in access to healthcare. This review aims to provide a comprehensive overview of the current state of HPV vaccines, including their mechanisms of action, safety profiles, and real-world efficacy. We will explore the impact of HPV vaccines on cancer prevention, examine the challenges related to vaccine distribution and uptake, and assess the role of public health policies in improving global vaccination rates. Additionally, the review will highlight the latest advancements in therapeutic HPV vaccines, ongoing research into next-generation vaccines, and the potential of HPV vaccination strategies in the context of personalized medicine. By examining these factors, we aim to provide insights into the future directions of HPV vaccination and its role in global public health.
Open AccessHuman Papillomavirus (HPV) Vaccination: Progress, Challenges, and Future Directions in Global Immunization Strategies
Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the efficacy of these vaccines, global immunization efforts still face several obstacles, including low vaccination coverage in low- and middle-income countries, vaccine hesitancy, and disparities in access to healthcare. This review aims to provide a comprehensive overview of the current state of HPV vaccines, including their mechanisms of action, safety profiles, and real-world efficacy. We will explore the impact of HPV vaccines on cancer prevention, examine the challenges related to vaccine distribution and uptake, and assess the role of public health policies in improving global vaccination rates. Additionally, the review will highlight the latest advancements in therapeutic HPV vaccines, ongoing research into next-generation vaccines, and the potential of HPV vaccination strategies in the context of personalized medicine. By examining these factors, we aim to provide insights into the future directions of HPV vaccination and its role in global public health.
- Open Access
RETRACTED: Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World
The family Paramyxoviridae includes a number of negative RNA viruses known for their wide host range and significant zoonotic potential. In recent years, there has been a surge in the identification of emerging zoonotic paramyxoviruses, particularly those hosted by bat species, which serve as key reservoirs. Among these, the genera Henipavirus and Pararubulavirus are of particular concern. Henipaviruses, including the highly pathogenic Hendra and Nipah viruses, have caused severe outbreaks with high mortality rates in both humans and animals. In contrast, zoonotic pararubulaviruses such as the Menangle virus typically induce mild symptoms or remain asymptomatic in human hosts. This review summarizes current knowledge on the evolution, ecology, and epidemiology of emerging zoonotic paramyxoviruses, focusing on recently discovered viruses and their potential to cause future epidemics. We explore the molecular mechanisms underlying host-switching events, viral replication strategies, and immune evasion tactics that facilitate interspecies transmission. In addition, we discuss ecological factors influencing virus emergence, including changes in bat populations and habitats and the role of wildlife–human interfaces. We also examine the public health impact of these emerging viruses, underlining the importance of enhanced surveillance, developing improved diagnostic tools, and implementing proactive strategies to prevent potential outbreaks. By providing a comprehensive overview of recent advances and gaps in knowledge, this review aims to inform future research directions and public health policies related to zoonotic paramyxoviruses.
Open AccessRETRACTED: Zoonotic Paramyxoviruses: Evolution, Ecology, and Public Health Strategies in a Changing World
The family Paramyxoviridae includes a number of negative RNA viruses known for their wide host range and significant zoonotic potential. In recent years, there has been a surge in the identification of emerging zoonotic paramyxoviruses, particularly those hosted by bat species, which serve as key reservoirs. Among these, the genera Henipavirus and Pararubulavirus are of particular concern. Henipaviruses, including the highly pathogenic Hendra and Nipah viruses, have caused severe outbreaks with high mortality rates in both humans and animals. In contrast, zoonotic pararubulaviruses such as the Menangle virus typically induce mild symptoms or remain asymptomatic in human hosts. This review summarizes current knowledge on the evolution, ecology, and epidemiology of emerging zoonotic paramyxoviruses, focusing on recently discovered viruses and their potential to cause future epidemics. We explore the molecular mechanisms underlying host-switching events, viral replication strategies, and immune evasion tactics that facilitate interspecies transmission. In addition, we discuss ecological factors influencing virus emergence, including changes in bat populations and habitats and the role of wildlife–human interfaces. We also examine the public health impact of these emerging viruses, underlining the importance of enhanced surveillance, developing improved diagnostic tools, and implementing proactive strategies to prevent potential outbreaks. By providing a comprehensive overview of recent advances and gaps in knowledge, this review aims to inform future research directions and public health policies related to zoonotic paramyxoviruses.
- Open Access
- 11 September 2024
- Published by MDPI AG in Microorganisms
- Vol. 12 (9) , 1874
Update of the Genetic Variability of Monkeypox Virus Clade IIb Lineage B.1
From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus’s evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus’s behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak’s trajectory.
- 11 September 2024
- Published by MDPI AG in Microorganisms
- Vol. 12 (9) , 1874
Open AccessUpdate of the Genetic Variability of Monkeypox Virus Clade IIb Lineage B.1
From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus’s evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus’s behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak’s trajectory.
- Open Access
Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies
Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.
Open AccessViral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies
Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host–pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host–pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.