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Purpose: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. Material and methods: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3 months before imaging, and a standardized histopathological score for fibrosis (F0–F4) and inflammatory activity (PPA0–4) was used as a reference. Statistical analysis included independent t test, Mann–Whitney U-test, and ROC (receiver operating characteristic) analysis. Results: T1 mapping values were significantly higher in patients with advanced fibrosis (F0–2 vs. F3–4; p < 0.015), significant fibrosis (F0–1 vs. F2–4; p < 0.005), and significant inflammatory activity (PPA 0–1 vs. PPA 2–4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). Conclusion: A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis B (CHB) is a significant public health issue worldwide, especially in the Middle East region. Around 8% to 20% of patients with CHB develop cirrhosis, which may progress to hepatocellular carcinoma. The significant morbidity and mortality associated with CHB denote the importance of high-quality treatment. Methods: We searched the PubMed, Medline, and Cochrane databases from inception to January 2024 to identify relevant studies. Search terms were generated using established treatment guidelines for CHB. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: In this narrative review, we evaluated the seven currently licensed antiviral therapies for chronic Hepatitis B treatment, including nucleos(t)ide analogs (NAs) and pegylated interferon-alpha (PEG-IFNα). NAs can be divided into two categories: high barrier to resistance and low barrier to resistance. Tenofovir disoproxil fumarate, tenofovir alafenamide, and entecavir are NAs with a high barrier to resistance. Telbivudine has shown promise in providing high efficacy with low viral resistance rates; however, it is not recommended because of insufficient evidence and lack of cost-effectiveness. Lamivudine and adefovir dipivoxil, despite being efficacious, have a low barrier to resistance, the primary reason they are no longer recommended. PEG-IFNα has high efficacy and can be completed in 48 weeks. It is not associated with resistance; however, it has been reported to have several systemic adverse effects. Conclusions: Current first-line NA treatments in the Middle East include entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide. These drugs are favored over other NAs because of their low rates of resistance. PEG-IFNα has superiority over NAs in inducing a more durable antiviral response and having a finite treatment duration. The main drawback of PEG-IFNα is an unfavorable safety profile. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.

A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the clinical importance and current issues of the major markers used in both the detection and prognosis of chronic hepatitis B. An important indicator of an ongoing and persistent infection is the hepatitis B surface antigen. Hepatitis B virus DNA quantification monitoring aids in assessing viral load and hepatic cancer risk. While limited evidence of liver damage is provided by alanine aminotransferase levels, the hepatitis B core antibody verifies acute infection. Seroconversion to the hepatitis B e antibody is linked to a lower risk of disease development, and the hepatitis B e antigen status is a critical prognostic factor. Treatment choices are guided by a biopsy of the liver or minimally invasive liver fibrosis detection. Genotypes of the hepatitis B virus and host variables influence the prognosis by adding to the disease’s variability. Noninvasive techniques to evaluate the severity of the disease are provided by serum markers of fibrosis, such as the fibrosis score based on four criteria and the aspartate aminotransferase-to-platelet ratio index. The requirement for indicators that distinguish between distinct viral phases and increase specificity in evaluating liver damage is one of the challenges facing chronic hepatitis B research. Even though it is quite difficult to find reliable biomarkers for resistance especially when it comes to hepatocellular cancer risk estimation, there are advanced methods, which include imaging and omics that can help in improving the accuracy of the diagnostics and prognosis. Interventions early point that improve patient outcomes are made possible using diagnostics and prognostics as they are quite effective in managing the complicated landscape of chronic hepatitis B. Key in addressing these challenges today and improving the diagnostic and prognostic markers in the future, particularly those that would support the development of successful treatment plans for people living with chronic hepatitis B virus (HBV), are scientific research, technological advances and collaborations.

Abstract Background Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. Case presentation Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. Discussion Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.

Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC. [ABSTRACT FROM AUTHOR]

Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2–9.2), 9.3 (8.8–10.0), 10.1 (9.4–10.7), 10.7 (9.9–11.2), and 12.0 (11.2–12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2–4) and advanced fibrosis (F3–4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with <60 years in all fibrosis stages. Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. Case presentation: Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. Discussion: Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA. [ABSTRACT FROM AUTHOR]

Background: The global burden of chronic hepatitis B remains high and the best possible treatment remains long-term viral suppression expecting cure. Methods: Total 154 patients of chronic hepatitis B (48 HBeAg positive, e + ve) treated with oral entecavir (0.5 mg/1 mg per day) were recruited from June 2007 and followed prospectively until December 2022 for persistent HBV DNA negativity, HBeAg and HBsAg loss/seroconversion and other liver and drug-related events in real-life settings. Results: The mean duration of therapy was 6.78 (2–14) years with 1364 person-years of follow-up. All patients were HBV DNA negative by 15 months and remained so until the last follow-up. As many as 16.7% lost HBeAg after eight to 13 years of therapy, but not HBsAg. The mean fall in serum HBsAg level per year was 0.158 log IU/mL, being significantly higher in e + ve patients at baseline and until two years of therapy. The decline was significant until six years in e + ve patients compared to two years in e − ve ones. None had biochemical or virological breakthrough (except eight defaulters), flares or any untoward effects. The incidence of liver-related events, hepatocellular carcinoma and death was 10.4%, 1.9% and 14.3%, respectively, and 5.2% deaths were liver-related whose predictors were presence of cirrhosis (log rank 46.5, p > 0.001) and higher HBsAg level > 4 log IU/mL (log rank 18.15, p < 0.001) at baseline. Conclusion: Long-term entecavir therapy provides additional benefits of continuous reduction of serum HBsAg levels beyond suppression of HBV DNA. [ABSTRACT FROM AUTHOR]

Summary: Chronic hepatitis virus infections remain a major public health problem, despite significant therapeutic advances over the past two decades. Considerable progress has been made in the treatment of chronic viral hepatitis, but continued efforts are needed to develop and bring to market new drugs to fill the gaps in the current therapeutic armamentarium. Thus, clinical trials to assess the safety and efficacy of these new therapeutic approaches, including the selection of reliable and objective treatment endpoints, are still needed. Virological biomarkers play an important role in the diagnosis, monitoring, and evaluation of antiviral treatment efficacy. They are often used as primary or secondary endpoints in the evaluation of new treatments for chronic viral hepatitis. However, these markers are not all equally informative. The aim of this review article is to provide a comprehensive overview of the available virological tests for chronic viral hepatitis due to hepatitis B, D, C and E viruses, the information they provide and lack, the specific challenges associated with each, and their use in clinical trials of new treatments.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development. [ABSTRACT FROM AUTHOR]

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60–80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants. [ABSTRACT FROM AUTHOR]

Chronic hepatitis delta (CHD) affects millions worldwide with many undiagnosed. It requires the presence of hepatitis B virus (HBV) for viral propagation, and those who are coinfected have a more rapid development of cirrhosis, hepatocellular carcinoma and fulminant liver failure. Treatments licensed for HBV have been ineffective in those with CHD. As an orphan disease, there is only one licensed treatment for CHD in Europe, which has relatively limited efficacy and viral control. This review focuses on current treatments, recent advances and unresolved issues in hepatitis delta management. Chronic hepatitis delta is a very serious liver disease caused by the hepatitis delta virus, which can only infect people who already have hepatitis B. Worldwide, about 15 to 20 million people are affected. The disease can lead to severe liver damage and liver cancer. Medications that work for hepatitis B do not work for hepatitis delta, and until recently, there were no specific treatments approved for it. A new drug called bulevirtide was approved in Europe in 2020, and the UK in 2023, and is showing promise in ongoing studies around the world. It offers hope for better management of the disease. However, it is a daily injection needed indefinitely. Many people do not completely clear the virus. This article discusses new treatment strategies, including combining bulevirtide with other drugs, to improve the lives of the people living with the condition. These approaches aim to either significantly reduce the virus in the liver or (ideally) get rid of it completely. Article highlights Background Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis, affecting 15–20 million people globally. The disease progresses rapidly and can lead to severe liver-related morbidity and mortality, with cirrhosis, liver cancer and fulminant liver failure. Hepatitis delta virus (HDV) relies on hepatitis B virus (HBV) for propagation. Drugs effective against suppressing HBV do not work against HDV. The first ever clinical guidelines were published on hepatitis delta management by the European Association for the Study of the Liver (EASL) in 2023. The first approved drug (bulevirtide) for HDV was approved in 2020 in Europe, and 2023 in the UK. It is currently not licensed in the USA. Current treatments Treatment aims to prevent liver damage and improve life quality, ideally aiming for a finite treatment duration with complete viral suppression. Pegylated interferon-alpha (peg-IFNα) has been the standard treatment for decades (although this is used off-label) but is limited by side effects and partial efficacy. After a finite therapy duration, viral levels often rebound either shortly after or years after. Bulevirtide offers a new treatment avenue by blocking the virus's entry into hepatocytes, but it may require combination with other drugs for better effectiveness. There are no stopping criteria for this medication and many experience viral rebound if treatment is stopped. Novel HDV therapies & targets Ongoing research targets various aspects of the HDV life cycle and the immune response to develop more effective treatments. Pegylated interferon-lambda (peg-IFN-L) shows promise due to fewer side effects compared with traditional interferons. However, recent clinical trials were terminated due to liver-related complications, and therefore safety and use need to be carefully re-examined. Lonafarnib, a drug inhibiting a critical viral process, shows potential in combination therapies, though side effects and optimal dosing need further research. Nucleic acid polymers (NAPs) and emerging treatments like monoclonal antibodies and siRNA are in development, targeting the viral components and processes more directly and potentially offering new treatment modalities. Unresolved issues in hepatitis delta There is no international consensus on screening for CHD, leading to underdiagnosis and delayed treatment. Some countries are now implementing reflex testing in those with hepatitis b which will increase detection rates of delta. Diagnostic tools have until recently lacked standardization and fail to capture the full diversity of HDV, which hampers effective management. Better pangenotypic assays are essential. The optimal end points for treatment are debated, with ongoing discussions about how best to measure treatment success and the relevance of viral load and liver enzyme levels. Conclusion HDV remains a complex viral infection with a significant impact on global health and lack of effective, widely applicable treatments. Recent advances in therapy and diagnostics are promising, but a finite cure remains elusive. Future perspective Future research needs to focus on understanding the virus-host interactions and the dynamics of co-infections, to develop targeted and effective treatments. [ABSTRACT FROM AUTHOR]

Introduction: Viral hepatitis and other liver-related diseases are mostly difficult to diagnose solely based on clinical regimes. Liver damage results in alterations in serum enzyme patterns which have been used to develop many enzyme-based assays. Aim and objectives: The major clinical consequences of chronic liver disease can be evaluated by liver function tests like bilirubin, gamma- glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine transaminase (ALT). Alanine transaminase and AST changes indicate leakage from damaged hepatocytes. The present study was conducted to compare the serum levels of GGT, AST, ALT, AST:ALT ratio, and bilirubin in patients with chronic hepatitis. Materials and methods: The study group comprised 100 clinically diagnosed patients with chronic hepatitis and 100 controls. Results: Case--control comparison showed statistically higher values of GGT (p < 0.01), AST (p < 0.05), ALT (p < 0.05), AST: ALT (p < 0.01), and bilirubin (p < 0.05) in cases and serum levels of GGT, AST: ALT, and bilirubin were sensitive and specific when various parameters were compared with each other in various hepatitis and controls. Conclusion: The present study indicates that the parameters GGT, AST, ALT, AST:ALT ratio, and bilirubin are associated with increased risk of hepatitis. [ABSTRACT FROM AUTHOR]

Lisbet Grønbæk,1– 3 Harmony Omeife,3 Lu Ban,4 Colin J Crooks,5 Timothy R Card,3,4 Peter Jepsen,1,3 Joe West3,4,6 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Medicine, Regional Hospital Horsens, Horsens, Denmark; 3Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK; 4National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK; 5Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK; 6Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Lisbet Grønbæk, Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus, 8200, Denmark, Tel +45 78450000, Fax +45 78453897, Email Lisbet.Groenbaek@clin.au.dkPurpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case–control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England.Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005– 2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status.Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03– 1.39).Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.Plain Language Summary: Autoimmune hepatitis is a chronic liver disease associated with genetic variants and environmental exposures, but the causes of autoimmune hepatitis remain unknown. Using registry data, we evaluated the association between tobacco smoking and the risk for autoimmune hepatitis. We found that tobacco smoking was associated with an increased risk of autoimmune hepatitis.Keywords: epidemiology, chronic hepatitis, risk factors, tobacco

This article discusses the different subfamilies and species of the Hepatitis E virus (HEV) and their impact on transplant patients. HEV belongs to the Orthohepevirinae subfamily and has four species: Paslahepevirus, Rocahepevirus, Chirohepevirus, and Avihepevirus. HEV-1 and HEV-2 infections are prevalent in developing countries and pose a high risk to pregnant women but do not lead to chronic hepatitis in immunosuppressed patients. In developed countries, HEV-3 and HEV-4 are more prevalent and can cause chronic infection in transplant patients, leading to cirrhosis if left untreated. Ribavirin is an effective treatment option for HEV infections, including Rocahepevirus. Rat HEV, a member of the Rocahepevirus species, has been identified as a cause of acute hepatitis and chronic infection in humans, particularly in immunosuppressed patients. Ribavirin has shown efficacy in treating Rocahepevirus infections. Overall, this article highlights the importance of understanding the different strains of HEV and their potential impact on transplant patients. [Extracted from the article]

Purpose: Quantitative diagnosis of the degree of fibrosis progression is currently a focus of attention for fatty liver in nonalcoholic steatohepatitis (NASH). However, previous studies have focused on either lipid droplets or fibrotic tissue, and few have reported the evaluation of both in patients whose livers contain adipose and fibrous features. Our aim was to evaluate fibrosis tissue and lipid droplets in the liver. Methods: We used an analytical method combining the multi-Rayleigh (MRA) model and a healthy liver structure filter (HLSF) as a technique for statistical analysis of the amplitude envelope to estimate fat and fibrotic volumes in clinical datasets with different degrees of fat and fibrosis progression. Results: Fat mass was estimated based on the non-MRA fraction corresponding to the signal characteristics of aggregated lipid droplets. Non-MRA fraction has a positive correlation with fat mass and is effective for detecting moderate and severe fatty livers. Progression of fibrosis was estimated using MRA parameters in combination with the HLSF. The proposed method was used to extract non-healthy areas with characteristics of fibrotic tissue. Fibrosis in early fatty liver suggested the possibility of evaluation. On the other hand, fat was identified as a factor that reduced the accuracy of estimating fibrosis progression in moderate and severe fatty livers. Conclusion: The proposed method was used to simultaneously evaluate fat mass and fibrosis progression in early fatty liver, suggesting the possibility of quantitative evaluation for discriminating between lipid droplets and fibrous tissue in the early fatty liver. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis, also called cirrhosis, have wide prevalence worldwide for long yeas. Recently, many treatments for liver cirrhosis made marked progress, especially the umbilical cord-derived mesenchymal stromal cells (UCMSC) therapy. However, limited recourses and potential immune-related issues become the obstacles on UCMSC popularization in clinic. Therefore, we took dental pulp stem cells (DPSCs) into the consideration, since autologous DPSCs can be easily obtained without any ethnic or immune-related issues that heterogenous UCMSCs could encounter. We systematically compared the effects of both cell types and found that DPSCs had similar results to UCMSCs in regulating inflammation and reversing hepatic fibrosis. In our study, co-culturing T cells and PBMSCs showed that DPSCs have the ability to inhibit the proliferation of inflammatory cells and downregulate relevant inflammatory factors. In vitro and in vivo sterility tests confirmed the bio-safety of DPSCs. Moreover, the 1 year-aged mouse model demonstrated that DPSCs successfully reversed hepatic fibrosis. Overall, DPSCs demonstrated comparable effectiveness to UCMSCs in regulating inflammation and reversing hepatic fibrosis, particularly in the aged mouse model that represents middle-aged and elderly humans. Since autologous DPSCs avoid potential immune-related issues that heterogenous UCMSCs could encounter, they may be a better choice for stem cell-related therapies. [ABSTRACT FROM AUTHOR]

To explore the clinical efficacy of armillariella oral solution in treating patients with chronic hepatitis and its impact on liver function and liver fibrosis. A total of 96 patients with chronic hepatitis admitted to the Sino Japanese Friendship Hospital of Jilin University from June 2018 to January 2021 were selected as the study subjects. They were randomly divided into an observation group and a control group with 48 patients each. The control group was treated with conventional drugs, while the observation group was treated with armillariella oral solution on the basis of the control group. The clinical efficacy, liver function, liver fibrosis indicators, and adverse reactions of the two groups of patients were compared. The total clinical effective rate in the observation group was higher than that in the control group (P<0.05); After treatment, the glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase(AST), γ-glutamyl-transferase (γ-GT) in the observation group were significantly lower than that of the control group (P<0. 05); After treatment, the hyaluronidase (HA), laminin (LN), type III procollagen (PC III) and type IV collagen (IV-C) in the observation group were significantly lower than those in the control group(P<0.05); There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). The efficacy of armillariella oral solution in treating patients with chronic hepatitis is significant, it can significantly improve the liver function of patients, alleviate the degree of liver fibrosis, and has no significant adverse reactions. [ABSTRACT FROM AUTHOR]

Chronic hepatitis (CH) encompasses a prevalent array of liver conditions that significantly contribute to global morbidity and mortality. Yiguanjian (YGJ) is a classical traditional Chinese medicine with a long history of medicinal as a treatment for CH. Although it has been reported that YGJ can reduce liver inflammation, the intricate mechanism requires further elucidation. We used network pharmacology approaches in this work, such as gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and network-based analysis of protein-protein interactions (PPIs), to clarify the pharmacological constituents, potential therapeutic targets, and YGJ signaling pathways associated with CH. Employing the random walk restart (RWR) algorithm, we identified GNAS, GNB1, CYP2E1, SFTPC, F2, MAPK3, PLG, SRC, HDAC1, and STAT3 as pivotal targets within the PPI network of YGJ-CH. YGJ attenuated liver inflammation and inhibited GNAS/STAT3 signaling in vivo. In vitro, we overexpressed the GNAS gene further to verify the critical role of GNAS in YGJ treatment. Our findings highlight GNAS/STAT3 as a promising therapeutic target for CH, providing a basis and direction for future investigations.

Annually increasing quantity of liver transplants and the growing population of long-survived recipients determine the relevance of late allograft dysfunction study. Variety of morphological and functional disorders of the transplanted liver complicates their timely diagnostics. Moreover, in some patients, serious graft damage may proceed for a long time without clinical manifestations and laboratory abnormalities.The review summarizes the structure, prevalence, risk factors and prognostic value of different liver allograft pathology determined by histological examination in the long term after transplantation.

Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC.

Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2–9.2), 9.3 (8.8–10.0), 10.1 (9.4–10.7), 10.7 (9.9–11.2), and 12.0 (11.2–12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2–4) and advanced fibrosis (F3–4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method.

Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein–Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia.

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment. [ABSTRACT FROM AUTHOR]

Background and Aims: Educational attainment is an essential socio‐economic indicator with broad implications for lifestyle behaviour and metabolic health. We aimed to investigate the causal effect of education on chronic liver diseases and the potential mediating pathways. Methods: We applied univariable Mendelian randomization (MR) to assess the causal associations between educational attainment and non‐alcoholic fatty liver disease (NAFLD) (cases/controls: 1578/307 576 in FinnGen; 1664/400 055 in UK Biobank), viral hepatitis (1772/307 382; 1215/403 316), hepatomegaly (199/222 728; 297/400 055), chronic hepatitis (699/301 014; 277/403 316), cirrhosis (1362/301 014; 114/400 055) and liver cancer (518/308 636; 344/393 372) using summary statistics of genome‐wide association studies from the FinnGen Study and the UK Biobank, respectively. We used two‐step MR to evaluate potential mediators and their mediation proportions in the association. Results: Meta‐analysis of inverse variance weighted MR estimates from FinnGen and UK Biobank showed that genetically predicted 1‐SD (4.2 years) higher education was causally associated with decreased risks of NAFLD (OR: 0.48; 95%CI: 0.37–0.62), viral hepatitis (0.54; 0.42–0.69) and chronic hepatitis (0.50; 0.32–0.79), but not hepatomegaly, cirrhosis and liver cancer. Nine, two and three out of 34 modifiable factors were identified as causal mediators in the associations of education with NAFLD, viral hepatitis and chronic hepatitis, respectively, including six adiposity traits (mediation proportion: 16.5%–32.0%), major depression (16.9%), two glucose metabolism‐related traits (2.2%–15.8%) and two lipids (9.9%–12.1%). Conclusions: Our findings supported the causal protective effects of education on chronic liver diseases and outlined mediating pathways to inform prevention and intervention strategies to reduce the burden of liver diseases, especially for individuals with lower education. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer is a significant health challenge worldwide, often developing in individuals with pre-existing conditions like chronic hepatitis and fatty liver. This study delves into the possible benefits of colchicine, a medication traditionally used to treat gout, in reducing the risk of developing liver cancer. By examining extensive health data from the China Medical University Hospital in Taiwan, we compared liver cancer development in two groups: one that used colchicine and another that did not. Our findings reveal that colchicine users had a 19% reduced risk of developing liver cancer, a promising indication that requires further investigation. If these findings are substantiated via further research, colchicine could become a valuable tool in preventing liver cancer, especially for those with liver conditions, potentially saving numerous lives and reducing the burden on healthcare systems. This study underlines the importance of exploring new uses for existing medications and highlights the potential impact of colchicine on liver cancer prevention. This could lead to newer, cost-effective strategies to mitigate the risks and impacts of liver cancer, bringing hope to millions worldwide. Background: Liver cancer and notably hepatocellular carcinoma (HCC), results in significantly high mortality rates worldwide. Chronic hepatitis and fatty liver, recognized precursors, underscore the imperative need for effective preventive strategies. This study explores colchicine, traditionally acknowledged for its anti-inflammatory properties and investigates its potential in liver cancer prevention. Methods: Utilizing the iHi Data Platform of China Medical University Hospital, Taiwan, this study analyzed two decades of medical data, incorporating 10,353 patients each in the Colchicine and Non-Colchicine cohorts, to investigate the association between colchicine use and liver cancer risk. Results: The study identified that colchicine users exhibited a 19% reduction in liver cancer risk, with a multivariable-adjusted odds ratio of 0.81 after accounting for confounding variables. Additionally, the influence of gender and comorbidities like diabetes mellitus on liver cancer risk was identified, corroborating the existing literature. A notable finding was that the prolonged use of colchicine was associated with improved outcomes, indicating a potential dose–response relationship. Conclusions: This study proposes a potential new role for colchicine in liver cancer prevention, extending beyond its established anti-inflammatory applications. While the findings are promising, further research is essential to validate these results. This research may serve as a foundation for future studies, aiming to further explore colchicine's role via clinical trials and in-depth investigations, potentially impacting preventive strategies for liver cancer. [ABSTRACT FROM AUTHOR]

Aim: Liver biopsy is the gold standard for demonstrating hepatic damage in patients with chronic hepatitis. In this study, the reproducibility of the Modified Ishak Histological Activity Index (MHAI), used in the histopathological evaluation of chronic hepatitis, between observers trained in different centers was investigated. Patients and Methods: A total of 64 liver needle biopsies were included in the study between 2020 and 2023. Sections of the cases stained with hematoxylin-eosin, silver and trichrome were re-evaluated under a light microscope by the investigator (İÇ) and re-scored according to MHAI. In statistical evaluation, Cohen's kappa statistics were applied using the SPSS 21.0 progr am. Results: When all cases are taken into consideration in statistical evaluation, kappa value is; MAI was found to be 0.02 (slight) for degree and 0.38 (fair) for stage. When the researcher's compatibility with other pathologists was evaluated, the kappa values in the grading were quite low and found to be incompatible. Although there were higher values (0.12-0.49) in the stage than in the degree, the fit was poor and moderate. However, pathologists with a long-term history of collaboration showed higher levels of compliance, highlighting the importance of ongoing exchange of information. Conclusion: This study highlights the need for a standardized approach to interpretation and application of MHAI scoring to increase reproducibility. [ABSTRACT FROM AUTHOR]

Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein--Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia. [ABSTRACT FROM AUTHOR]

Chronic inflammation is linked to carcinogenesis, particularly in the digestive organs, i.e., the stomach, colon, and liver. The mechanism of this effect has, however, only partly been focused on. In this review, we focus on different forms of chronic hepatitis, chronic inflammatory bowel disease, and chronic gastritis, conditions predisposing individuals to the development of malignancy. Chronic inflammation may cause malignancy because (1) the cause of the chronic inflammation is itself genotoxic, (2) substances released from the inflammatory cells may be genotoxic, (3) the cell death induced by the inflammation induces a compensatory increase in proliferation with an inherent risk of mutation, (4) changes in cell composition due to inflammation may modify function, resulting in hormonal disturbances affecting cellular proliferation. The present review focuses on chronic gastritis (Helicobacter pylori or autoimmune type) since all four mechanisms may be relevant to this condition. Genotoxicity due to the hepatitis B virus is an important factor in hepatocellular cancer and viral infection can similarly be central in the etiology and malignancy of inflammatory bowel diseases. Helicobacter pylori (H. pylori) is the dominating cause of chronic gastritis and has not been shown to be genotoxic, so its carcinogenic effect is most probably due to the induction of atrophic oxyntic gastritis leading to hypergastrinemia. [ABSTRACT FROM AUTHOR]

Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID‐19, LSEC endotheliopathy induced by interleukin (IL)‐6 trans‐signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL‐6 trans‐signaling promotes the expression of intercellular adhesion molecule‐1, chemokine (C‐X‐C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P‐selectin, E‐selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease. [ABSTRACT FROM AUTHOR]

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development.

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60–80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.

Recently it has been established that cytokines are involved in the regulation of the body’s defense reactions in response to a pathogen and form an independent system for regulating homeostasis. The aim of this work is to study the relationship of the polymorphic marker TNFα (rs1800620) with its quantitative content and the degree of liver fibrosis in patients with various chronic hepatitis (VHC, VHB, VHB+C). The 82 patients with chronic hepatitis B, 62 patients with hepatitis B+C, and 100 patients with chronic hepatitis C were examined. GGTNFα (rs1800620) genotype is protective for patients with various viral hepatitis, and the GATNFα (rs1800620)and AATNFα (rs1800620)genotypes are profibrogenic for patients with chronic hepatitis B, chronic hepatitis B+C and chronic hepatitis C, respectively, since a high degree of fibrosis than in carriers of the homozygous GGTNFα (rs1800620)genotype. It is possible that the rate of fibrosis progression is influenced not only by the qualitative content of TNFα, but also by a certain genotype.

IntroductionAlthough most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.Materials and methodsUsing the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.ResultsA total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90–1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91–1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11–1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24–1.75).ConclusionWe report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels.

Background Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation. Methods Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis. Results AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3). Conclusions The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) infection represents the most serious form of chronic hepatitis. Turkey is among the countries with high HDV and intermediate hepatitis B virus prevalence. In Turkey, hepatitis B virus (HBV) vaccine series was included in the routine vaccination program in 1998. There have been regional differences in prevalence of HBV and HDV. Although a decline in HDV prevalence is estimated, there are uncertainties about the epidemic patterns of it. HDV prevalence was studied in varying groups and geographic regions. In this study, we aimed to analyse hepatitis D epidemiology in all groups and geographic regions in recent 35 years. During the study period of 35 years, 111 publications were noted. The analysis was done on the basis of three periods: 1999 and before (Period 1), 2000–2009 (Period 2), and 2010 and after (Period 3). The groups studied included inactive carrier state, chronic hepatitis B, all HBsAg‐positive individuals and special groups. Among inactive HBV carriers, HDV prevalence did not change significantly over three decades. Among patients with chronic hepatitis, studies reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. The studies including all HBsAg‐positive patients reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups were taken to reveal HDV prevalence in HBV‐infected patients, and it showed decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups analysed according to the geographic regions of the country showed that Eastern and Southeastern Anatolia regions still have a high burden of HDV. The study showed that although HDV prevalence decreased from 8.3% in Period 1 to 4.8% in Period 2, it tended to increase 5.5% in Period 3. HDV infection is still a healthcare problem in Turkey. [ABSTRACT FROM AUTHOR]

There are currently 250 million people infected with the hepatitis B virus (HBV) worldwide, despite the availability of a prophylactic vaccine for many years and the use of efficient and well-tolerated viral suppressive drugs since 1998. In this review, I go through the most recent developments in the structure, and epidemiology and biology of the virus, look at changes in the way the disease is currently being treated, and investigate novel, cutting-edge treatments that are being developed for the treatment of HBV infection. Genotypes and serological subtypes have a strong and statistically significant association, and in some circumstances, serological subtypes can be utilized to distinguish between sub genotypes. geographic distribution of certain genotypes and subgenotypes varies and plays a crucial role in the clinical manifestation of infection as well as the response to antiviral medication. Thanks to advancements in genetics, the prospect for vaccinations, and tailored management to target the integration of virus with host. HBV persistence occurs due to covalently closed circular DNA can rarely be removed by current pharmacological therapies. Alternative treatment approaches, such as those built on silencing of viral. According to reports, HBV DNA levels can be inhibited and conversion of HBeAg to antibody to HBe Ag can be induced by antiviral medication like nucleotide analog (NUC), which can prevent liver-related death. Additionally, there is a critical need for the creation of global archives of standardized HBV reagents and protocols that can be accessible by all HBV researchers. The plan for HBV cure research presented in this position paper will make a significant contribution to the objective of eradicating HBV infection globally. [ABSTRACT FROM AUTHOR]

FcγR is expressed by many immune cells and plays an important role in the immune response to hepatitis B virus (HBV) infection. CD32 belongs to the FcγR family. This study aimed to observe changes in CD32 expression by CD4+ T and CD8+ T lymphocytes in chronic HBV infection patients and evaluate the clinical utility of CD4+ T and CD8+ T CD32 expression to assess the severity of liver injury in chronic HBV-infected patients. A total of 68 chronic HBV patients and 40 healthy individuals were recruited, and the median fluorescence intensity (MFI) of CD32 expression on CD4+ T, CD8+ T lymphocytes was measured using flow cytometry and the CD4+ T, CD8+ T CD32 index was calculated. The reactivity of the healthy individual lymphocytes to mixed patients' plasma containing HBV was observed. Finally, the correlation between CD4+ T, CD8+ T lymphocytes CD32 MFI and liver function indicator levels was analyzed. The CD4+ T, CD8+ T CD32 MFI and index were significantly elevated in HBV patient groups than in normal control group (p < 0.001, for all). Furthermore, the CD32 MFI of healthy persons' CD4+ T and CD8+ T lymphocytes were remarkably increased when stimulated with mixed patients' plasma containing high HBV copies (p < 0.001; P < 0.001). More importantly, in HBV patients, there was a significant positive correlation between CD4+ T, CD8+ T CD32 MFI and the level of serum aspartate aminotransferase (p < 0.05, p < 0.05). In conclusion, the increased expression of CD32 on CD4+ T and CD8+ T lymphocytes might be potential promising biomarkers for the severity of liver function impairment in chronic HBV patients. [ABSTRACT FROM AUTHOR]

Background: Ubiquitously spread hepatitis B virus (HBV) is one of the leading causes of end-stage liver disease. Chronic HBV infection presents with different outcomes including cure, chronic carriers, and death. Objectives: To assess the clinical profile and outcomes of hepatitis B patients admitted in a tertiary care teaching hospital in Mumbai, India. Materials and Methods: This was a single-center, observational, prospective study conducted over a period of 18 months at the medical and gastroenterology wards of King Edward Memorial Hospital, Mumbai, India. All the newly diagnosed patients of hepatitis B infection aged more than 12 years, admitted during the study duration in the medical and gastroenterology wards were included in the study. Results: A total of 77 patients were studied. The clinical presentations of the patients were: abdominal distension (28.6%), jaundice (24.7%), loss of appetite (24%), pallor (18.2%), leg swelling (16%), gastrointestinal bleeding (11%), fever (11%), altered sensorium (10.4%) malena (9%), hepatic failure (7.8%), hematemesis (7.7), abdominal pain (5%), and oliguria (1%). The associated co-morbidities included: diabetes mellitus (15%), chronic kidney disease (18%), hypertension (19.5%), pulmonary tuberculosis (6.4%), and anemia of chronic disease (5%). Following investigations and treatments, 9.09% achieved cure, 79.22% progressed to chronicity, and 11.09% died. Conclusion: The clinical profile of patients with hepatitis B infection in India is varied and associated with some co-morbidities. Less than one tenth of the patients achieve complete cure while majority progress to chronicity. There is need for improvement in public health enlightenment campaign and quality of care for hepatitis B infection in view of the poor outcomes observed in this study.

Abstract Background Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. Methods This cross-sectional study included 50 children, 5–18 years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. Results The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. Conclusion APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

Abstract Background Copper associated hepatopathy (CAH) has become an important and prevalent disease since the 1990's, coincidental with changes in copper (Cu) content in commercial dog foods. Knowing the demographic and histopathologic features related to hepatic Cu concentrations might aid in diagnosing CAH in dogs. Hypothesis/Objectives The primary aim was to identify demographic and histopathologic features associated with abnormally high hepatic Cu concentrations. Animals Dogs that underwent liver histopathology and Cu quantification at a veterinary diagnostic laboratory between July 2010 and February 2020. Methods Data was retrospectively collected from an electronic database. A Gaussian multiple regression model on the log scale was used to evaluate associations between hepatic Cu and a set of demographic and histologic features selected with machine learning methods. Results Of 4559 cases meeting criteria, 50% had hepatic Cu > 400 and 19% had Cu > 1000 ppm (parts per million) dry weight (reference range 120‐400). Median hepatic Cu was 391 ppm, range 4.5 to 31500. Age was negatively associated (P

Abstract Background The purpose of this study was to compare the diagnostic value of serum oligosaccharide chain (G-test), alpha-fetoprotein (AFP) and aspartic aminotransferase to alanine aminotransferase ratios (AAR), both alone and in combination, for predicting hepatocellular carcinoma (HCC) onset. Methods Between Januarys 2020–2022, 152 subjects admitted to the First Affiliated Hospital of Nanchang University was enrolled in this study, of which 77 had HCC, 18 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 20 were healthy. Data for patient characteristics were collected, and differences between groups were analyzed by either Mann-Whitney U or χ2 tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of AFP, G-test, and AAR for HCC. Results G-test, AFP, and AAR were all found to have close correlations with HCC among the different patient groups, with G-test being the most predictive for HCC among healthy and CL patients, as represented by respective areas under the curve (AUC) of 0.953 and 0.792 (P

Abstract Background The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). Methods Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein − protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. Results A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. Conclusion Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.

Objective: Infectious mononucleosis is a relatively common acute presentation to the ENT department. There is an expected derangement in the liver function test results in most patients. There is no guidance regarding follow up, and practice varies. This study aimed to evaluate the utility of liver function tests and abdominal ultrasound in infectious mononucleosis. Methods: This was a retrospective study of all adult patients admitted under ENT with infectious mononucleosis over a five-year period. Results: A total of 153 patients were included; 80 per cent had abnormal liver function test results at presentation. Around 50 per cent had at least one liver function test assessment following discharge. Median (interquartile range) time to resolution of liver function test results was 32 days (20–50 days); maximum time was 10 months. Six patients had in-patient abdominal ultrasound: all showed a normal liver and biliary tree. No patient developed any liver disease sequelae. Conclusion: The findings suggest that serial assessment of liver function is not required in immunocompetent adults with subclinical derangement in liver function. [ABSTRACT FROM AUTHOR]

To characterize viral hepatitis co‐infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low‐income refugees consecutively evaluated for a clinical consultation at one of the five first‐level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti‐hepatitis C virus (HCV) and anti‐HIV; the HBsAg‐positive were screened also for anti‐delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg‐positive alone (Control group B), 85 (2.9%) only anti‐HCV‐positive (Control group C), 16 (0.5%) HBsAg/anti‐HCV‐positive (Case group BC), and 8 (0.2%) HBsAg/anti‐HDV‐positive (Case group BD). Moreover, 57 (1.9%) subjects were anti‐HIV‐positive. HBV‐DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV‐RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co‐infections in the immigrant population. [ABSTRACT FROM AUTHOR]