The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time.

We utilized the N3C level 3 data set with uncensored dates to identify all patients with chronic liver disease (CLD) with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared with infection at the onset of the COVID-19 pandemic.

We identified 117,811 total patients with CLD infected with SARS-CoV-2 between March 2020 and November 2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1016) for patients with CLD without cirrhosis and 6.3% (1732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared with infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95% confidence interval [CI], 0.08-0.50) for patients with CLD without cirrhosis and 0.35 (95% CI, 0.18-0.69) for patients with CLD with cirrhosis.

In this N3C study, we found that the observed 30-day CFR decreased progressively for patients with CLD both with and without cirrhosis, consistent with broader trends seen in the general population.

To investigate the symptoms, the level of antibody, the progression of liver disease after SARS-CoV-2 infection in middle-aged and elderly population infected with hepatitis virus.

The study was based on a cohort of high-risk liver cancer and the participants was recruited in April 2023. Blood sample were collected and information was obtained through questionnaires. Data on reinfection was obtained by follow-up until July 31, 2023. The SARS-CoV-2-specific neutralizing antibody and IgG were measured.

A total of 599 participants infected with hepatitis virus were included and the mean age was 61.3 ± 7.4 years. The SARS-CoV-2 infection rate was 94.7%. Among the infected, 132 were asymptomatic, 435 were symptomatic, no severe cases occurred. Four months after infection, no difference was in liver function and aMAP score between the infected and uninfected. The infected had higher seropositivity rates of both antibodies than the uninfected (neutralizing antibody: uninfected: 93.7%, infected: 99.6%; IgG: uninfected: 59.4%, infected: 98.9%). The levels of both antibodies in the symptomatic were higher than those the asymptomatic and the uninfected (neutralizing antibody: uninfected: 0.75 AU/mL, asymptomatic: 15.46 AU/mL, symptomatic: 24.76 AU/mL; IgG: uninfected: 15.10 AU/mL, asymptomatic: 263.84 AU/mL, symptomatic: 291.83 AU/mL). By July 31, 2023, the incidence of reinfection was 17.5%.

Although the infection rate of SARS-CoV-2 was high, no severe cases occurred. Omicron infection may not aggravate progression of hepatitis. Four months after infection, the population showed high positivity rate in neutralizing antibody and IgG. Monitoring of virus mutations and targeted prevention and care strategies is crucial for vulnerable populations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in patients with coronavirus disease 2019 (COVID-19). Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19-related liver pathology and developing targeted therapies. This editorial discusses the significance of ACE2 in hepatic SARS-CoV-2 infection, drawing on the research by Jacobs et al. Their findings indicate that hepatic ACE2 expression, frequency of hepatic SARS-CoV-2 infection, and severity of liver injury are elevated in patients with pre-existing chronic liver diseases. These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.

The risk of microbial infections is increased in cirrhosis and other forms of advanced liver disease such as alcohol-associated hepatitis. Such infections may precipitate new or further decompensation and death, especially in patients with clinical features of acute-on-chronic liver failure. The severe immune dysfunction or "immune paralysis" caused by advanced liver disease is associated with high short-term mortality. However, the pathogenic mechanisms underlying immune dysfunction and immunodeficiency are incompletely understood. Evidence to date suggests a complex, dynamic process that perturbs the physiological roles of the liver as a master regulator of systemic immunity and protector against noxious effects of exogenous molecules in the portal vein flowing from the gut. Thus, in cirrhosis and severe alcohol-associated hepatitis, the ability of hepatocytes and intrahepatic immune cells to balance normal context-dependent dichotomous responses of tolerance vs immune activation is lost. Contributing factors include loss of the gut barrier with translocation of microbial products through the portal vein, culminating in development of functional defects in innate and adaptive immune cells, and generation of immune-regulatory myeloid cells that permit microbial colonization and infection. This review addresses key evidence supporting the paradigm of immune dysfunction as a risk for microbial infections and identifies potential therapeutic targets for intervention. The primary focus is on cirrhosis-associated immune dysfunction and alcohol-associated liver disease, because the bulk of available data are from these 2 conditions.

We assessed the global incidence, mortality, and disability-adjusted life years (DALYs) associated with various liver diseases, including alcohol-related liver disease (ALD), hepatitis B/C virus infections (HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index (SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD, along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States (U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world.

There is conflicting evidence regarding the impact of chronic hepatitis B virus (HBV) on SARS-CoV-2 outcomes. Additionally, the impact of SARS-CoV-2 vaccination and variant periods on outcomes in HBV/SARS-CoV-2 coinfection remain unexplored.

We utilized the TriNetX database to compare adults with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) across 97 US healthcare systems from 2020 to 2023. We assessed the odds of all inpatient hospitalizations, intensive care unit admissions, mechanical ventilation, 30-day, 90-day, and overall mortality. In sensitivity analyses, we excluded HIV, hepatitis C virus, and transplant cases and stratified the HBV/SARS-CoV-2 cohort by cirrhosis status. We applied propensity score matching to address confounding and reported odds ratios (OR) with 95% confidence intervals (CI).

Of 4 206 774 individuals with SARS-CoV-2, about 0.2% (8293) were HBV/SARS-CoV-2. Individuals with HBV/SARS-CoV-2 (vs SARS-CoV-2 alone) had higher odds of intensive care unit admissions (OR, 1.18; 95% CI, 1.02-1.36), 90-day (OR, 1.22; 95% CI, 1.01-1.41) and overall mortality (OR, 1.18; 95% CI, 1.06-1.33). In sensitivity analyses, those with HBV/SARS-CoV-2 and cirrhosis had a 2.0- to 2.50-fold higher odds of adverse outcomes. Notably, even individuals with HBV/SARS-CoV-2 without cirrhosis had higher odds of mortality. Vaccinated (vs unvaccinated) individuals with HBV/SARS-CoV-2 had 57%, 54%, and 29% reduction in 30-day, 90-day, and overall mortality, respectively. The pre-Delta variant period was associated with higher odds of hospitalization compared to the Omicron but not the Delta period.

Chronic HBV was associated with worse SARS-CoV-2 outcomes, whereas SARS-CoV-2 vaccination reduced the likelihood of adverse outcomes.

Cirrhosis has been pointed out as a clinical entity that leads to worse clinical prognosis in COVID-19 patients. However, this concept is controversial in the literature. We aimed to evaluate clinical outcomes by comparing patients with cirrhosis to those without cirrhosis in a Brazilian cohort.

Data from 20,164 COVID-19 inpatients were collected from 41 hospitals in Brazil between March to September 2020 and March 2021 to August 2022. We compared 117 patients with cirrhosis to 632 matched controls. A propensity score model was used to adjust for potential confounding variables, incorporating some predictors: age, sex at birth, number of comorbidities, hospital of admission, whether it was an in-hospital clinical manifestation of COVID-19, and admission year. Closeness was defined as being within 0.16 standard deviations of the logit of the propensity score.

The median age was 61 (IQR 50-70) years old, and 63.4% were men. There were no significant differences in the self-reported symptoms. Patients with cirrhosis had lower median hemoglobin levels (10.8 vs. 13.1 g/dl), lower platelets (127,000 vs. 200,000 cells/mm3), and leukocyte counts, as well as lower median C-reactive protein (63.0 vs. 76.0 p = 0.044) when compared to controls. They also had higher mortality compared to matched controls (51.3% vs. 21.7%, p < 0.001). They also had higher frequencies of admission in an intensive care unit (51.3% vs. 38.0%, p = 0.007), invasive mechanical ventilation (43.9% vs. 26.6%, p < 0.001), dialysis (17.9% vs. 11.1%, p = 0.038), septic shock (23.9% vs. 14.9%; p = 0.015) and institution of palliative care (19.7% vs. 7.4%; p < 0.001).

This study has shown that COVID-19 inpatients with cirrhosis had significantly higher incidence of severe outcomes, as well as higher frequency of institution of palliative care when compared to matched controls. Our findings underscore the need for these patients to receive particular attention from healthcare teams and allocated resources.

In coronavirus disease 2019 (COVID-19), older age and co-morbidities are associated with mortality. Among liver disease aetiologies alcoholic liver disease was associated with mortality. Chronic hepatitis delta (CHD) had not been studied. The current study explores course of COVID-19 disease in chronic hepatitis B (CHB) and CHD. This retrospective study included CHB and CHD patients from the gastroenterology departments of Hacettepe and Koç University Hospitals. COVID-19 was confirmed via PCR testing for SARS-CoV-2 RNA. Data on liver disease severity, including MELD-Na and Child-Pugh scores, as well as vaccination status, were collected. A total of 618 patients (343 M/275 F) were evaluated, comprising 540 CHB patients (27 [5%] cirrhotic) and 78 CHD patients (43 [55%] cirrhotic). COVID-19 was diagnosed in 47 CHB patients (8.7%) and 12 CHD patients (15.4%), p = NS. Hepatic reactivation occurred in 3 CHB patients (6.3%) and 4 CHD patients (33%), (p = 0.018). Reactivation was more frequent in cirrhotic patients than non-cirrhotic patients (50% vs. 4%, p = 0.0009). One cirrhotic CHB patient decompensated, while one cirrhotic CHD patient died and another developed hepatic decompensation. The majority of cirrhotic CHB patients (96.3%) were receiving nucleos(t)ide analogues (NAs), whereas only one cirrhotic CHD patient was on treatment for Hepatitis D virus (HDV). Although the small number of CHD patients and COVID-19-positive cases limits definitive conclusions, CHD patients may experience a more severe course of COVID-19 compared to CHB patients. This may be due to the higher proportion of cirrhotics among CHD patients and the lack of effective antiviral treatment for HDV.

SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing liver conditions experience more severe disease. While it was known that SARS-CoV-2 infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication and spread, and highlights direct hepatocyte damage. Viral replication was readily detectable upon infection of primary human hepatocytes and hepatoma cells with the ancestral SARS-CoV-2, Delta, and Omicron variants. Hepatocytes express the SARS-CoV-2 receptor ACE2 and the host cell protease TMPRSS2, and knocking down ACE2 and TMPRSS2 impaired SARS-CoV-2 infection. Progeny viruses released from infected hepatocytes showed the typical coronavirus morphology by electron microscopy and proved infectious when transferred to fresh cells, indicating that hepatocytes can contribute to virus spread. Importantly, SARS-CoV-2 infection rapidly induced hepatocyte death in a replication-dependent fashion, with the Omicron variant showing faster onset but less extensive cell death. C57BL/6 wild-type mice infected with a mouse-adapted SARS-CoV-2 strain showed high levels of viral RNA in liver and lung tissues. ALT peaked when viral RNA was cleared from the liver. Liver histology revealed profound tissue damage and immune cell infiltration, indicating that direct cytopathic effects of SARS-CoV-2 and immune-mediated killing of infected hepatocytes contribute to liver pathology.

Alcohol-associated liver disease (ALD), as highlighted in this narrative review, is a major public health concern, increasingly impacting global disease burden and premature mortality. In 2019, ALD accounted for the loss of 11 million life-years worldwide. The rising number of deaths and disability-adjusted life-years attributed to ALD, particularly pronounced in the United States, are alarming. Projections suggest that the economic impact of ALD, as seen in the United States, could potentially double by 2040. ALD is increasingly prevalent among younger adults (20-45 y) and has become the leading cause of liver transplantation in both United States and Europe. During the COVID-19 pandemic, the existing trend was further amplified as high-risk drinking patterns coincided with a rise in hospital admissions for alcohol-associated hepatitis and increased ALD-related mortality. The prevalence of ALD is estimated at 3.5% in the general population, 26.0% among hazardous drinkers, and 55.1% among those with alcohol use disorders. Alarmingly, 5-year mortality rates for patients with ALD exceed 50%, with even higher rates in more advanced disease stages. Methodological challenges, such as underreporting, diagnostic difficulties, and variability in registry data quality, complicate the accurate assessment of the impact of ALD. Additionally, the contribution of alcohol to the progression of other liver diseases is often under acknowledged in health care registries, leading to a significant underestimation of its broader implications for liver health. Addressing the growing ALD concern requires robust public health initiatives, heightened awareness, refined diagnostic techniques, and comprehensive epidemiological studies. These measures are vital to tackle the increasing prevalence of ALD and mitigate its extensive impact on individuals and health care systems.

This review aimed to assess the safety and efficacy of SARS-CoV-2 vaccines in patients with chronic liver disease (CLD).

Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science were searched from 2020 to 2024. Data was extracted following Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The random-effects model (when I2 ≥ 50%) or fixed effect model (I2 < 50%) was used.

29 studies were included in this review. Compared to healthy controls (HCs), patients with CLD had a higher incidence of mild adverse events (RR = 1.60, p < 0.001), while the incidence of severe adverse events was similar (RR = 1.08, p = 0.92). Seropositivity rates of three antibodies in patients were lower than in HCs [neutralizing antibody (RR = 0.86, p = 0.002), anti-spike antibody (RR = 0.97, p = 0.06) and anti-receptor binding domain antibody (RR = 0.95, p = 0.04)]. Compared to unvaccinated patients, vaccinated patients had lower rates of SARS-CoV-2 infection, hospitalization and death (p ≤ 0.05).

SARS-CoV-2 vaccines showed good safety and efficacy in CLD patients, but antibody response appeared to be decreased. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in this vulnerable population.

Limited research suggested that liver cirrhosis is an independent risk factor for severe COVID-19, leading to higher hospitalization and mortality rates. This study aimed to identify the prognostic factors and validate scoring systems for predicting mortality in COVID-19 patients with liver cirrhosis.

This retrospective cohort study extracted electronic health records of patients with COVID-19 who visited the emergency department between April 2021 and September 2022. Adult COVID-19 patients with liver cirrhosis were included, excluding those aged < 18 years and who did not require hospitalization. The primary outcome was in-hospital mortality. The effectiveness of the scoring systems were analyzed for COVID-19 in-house mortality prediction.

A total of 1,368 adult COVID-19 patients with liver cirrhosis were included in this study. Compared with the survival group, the non-survival group had lower vital signs such as systolic blood pressure and blood oxygen saturation, higher levels of white blood cells, creatinine, bilirubin, and C-reactive protein, and longer prothrombin time. Higher rates of intubation, oxygen use, and dexamethasone use were observed in the non-survivor group. The WHO ordinal scale, MELD, and MELD-Na scores showed good predictive ability for in-hospital mortality.

The WHO ordinal scale showed the best performance in predicting mortality in patients with cirrhosis and COVID-19. MELD and MELD-Na scores were also found good performance for mortality prediction. Coagulation function, intubation, and dexamethasone administration were the most significant prognostic factors.

This review explores the mechanisms, diagnostic approaches, and management strategies for COVID-19-induced liver injury, with a focus on its impact on patients with pre-existing liver conditions, liver cancer, and those undergoing liver transplantation.

A comprehensive literature review included studies on clinical manifestations of liver injury due to COVID-19. Key areas examined were direct viral effects, drug-induced liver injury, cytokine storms, and impacts on individuals with chronic liver diseases, liver transplants, and the role of vaccination. Data were collected from clinical trials, observational studies, case reports, and review literature.

COVID-19 can cause a spectrum of liver injuries, from mild enzyme elevations to severe hepatic dysfunction. Injury mechanisms include direct viral invasion, immune response alterations, drug toxicity, and hypoxia-reperfusion injury. Patients with chronic liver conditions (such as alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma) face increased risks of severe outcomes. The pandemic has worsened pre-existing liver conditions, disrupted cancer treatments, and complicated liver transplantation. Vaccination remains crucial for reducing severe disease, particularly in chronic liver patients and transplant recipients. Telemedicine has been beneficial in managing patients and reducing cross-infection risks.

This review discusses the importance of improved diagnostic methods and management strategies for liver injury caused by COVID-19. It emphasizes the need for close monitoring and customized treatment for high-risk groups, advocating for future research to explore long-term effects, novel therapies, and evidence-based approaches to improve liver health during and after the pandemic.

Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied.

We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2-4 weeks following a fourth dose of XBB.1.5 mRNA vaccines.

Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05).

XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks.

In this work, we developed a novel microfluidic paper-based analytical device to quantify the blood markers of liver function from human fingertips and whole blood samples. The device can quickly acquire information for screening liver injury and supporting clinical decision-making by simultaneously performing quantitative tests for alanine aminotransferase, aspartate aminotransferase, and albumin. We evaluated the detection accuracy and the storage stability of the device using fingertip samples. The yielded results of our device correlated well with those from Mindray BS350s, even under the conditions of 35 °C and 90%RH. Thus, it offers an effective platform for clinical assessment of liver injury particularly in resource-limited areas.

Three years after the beginning of the SARS-CoV-2 pandemic, the safety and efficacy of COVID-19 vaccination in liver cirrhosis (LC) patients remain controversial. We aimed to study the safety, immunological, and clinical responses of LC patients to COVID-19 vaccination.

Prospective multicentric study in adults with LC eligible for COVID-19 vaccination, without prior known infection. Patients were followed up until the timing of a booster dose, SARS-CoV-2 infection, or death. Spike-protein immunoglobulin G antibody titers for SARS-CoV-2 at 2 weeks, 3 months, and 6 months postvaccination were assessed. Antibody titers <33.8 binding antibody units (BAU)/mL were considered seronegative and <200 BAU/mL suboptimal. Postvaccination infection and its severity were registered.

We included 124 LC patients, 81% males, mean aged 61 ± 10 years, with a mean follow-up of 221 ± 26 days. Alcohol was the most common (61%) cause of cirrhosis, and 7% were under immunosuppressants for autoimmune hepatitis; 69% had portal hypertension, 42% had a previous decompensation, and 21% had a Child-Pugh-Turcotte score of B/C. The type of vaccine administrated was BNT162b2 (n = 59, 48%), ChAdOx1nCoV-19 (n = 45, 36%), mRNA-1273 (n = 14, 11%), and Ad26.COV2.S (n = 6, 5%). Eighteen percent of the patients reported adverse events after vaccination, none serious. Median [Q1; Q3] antibody titers were 1,185 [280; 2,080] BAU/mL at 2 weeks, 301 [72; 1,175] BAU/mL at 3 months, and 192 [49; 656] BAU/mL at 6 months. There were seronegative and suboptimal antibody responses in 8% and 23% of the patients at 2 weeks, 16% and 38% at 3 months, and 22% and 48% at 6 months. Older age and adenovirus vector vaccines were the only factors associated with seronegative and suboptimal responses at 2 weeks and 3 months (p < 0.05) in a multivariable logistic regression analysis. Eleven patients (9%) were infected with SARS-CoV-2 during follow-up (3.8-6.6 months postvaccination), all with mild disease. There were no differences regarding the type of vaccine, and 73% had antibody titers >200 BAU/mL at 3 months.

COVID-19 vaccines in patients with LC were safe, without serious adverse events. The humoral and clinical responses were similar to the reported for the general population. Humoral response was adversely impacted by older age and adenovirus vector vaccines and unrelated to the liver disease severity.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

In recent years, magnetic nanoparticles (MNPs) have exhibited theragnostic characteristics which confer a wide range of applications in the biomedical field. Consequently, through Alternating Current Biosusceptometry (ACB), magnetic nanoparticles can be used as tracers, allowing the study of healthy and cirrhotic livers and providing the ability to differentiate them through the reconstruction of quantitative images. The ACB system consists of a developing biomagnetic technique that has the ability to magnetize and measure the magnetic susceptibility of a material such as MNPs, thereby offering quantitative information about biological systems with magnetic tracers.

The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence.

To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC).

Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People's Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias.

We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM.

Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.

Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.

The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.

Patients with cirrhosis are more susceptible to coronavirus disease 2019 (COVID-19) due to immune dysfunction. In this retrospective study we aimed to investigate whether suppression of mild systemic inflammation with selective cyclooxygenase-2 inhibitor (COX-2-I) during chronic care of cirrhotic patients would reduce the occurrence of acute decompensated events and improve patient prognosis of COVID-19.

Medical records of cirrhotic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were sequentially reviewed. The patients were divided into the COX-2-I and control groups depending on whether they took oral selective COX-2-I for over 3 months or not. The primary outcomes included the occurrence of severe/critical COVID-19, acute decompensated events, and acute-on-chronic liver failure (ACLF).

After propensity score matching analysis, there were 314 cases in the control group and 118 cases in the COX-2-I group. Compared with the control group, the risk of severe/critical COVID-19 in the COX-2-I group was significantly decreased by 83.1% (p = 0.004). Acute decompensated events and ACLF occurred in 23 (7.32%) and nine (2.87%) cases in the control group, but none in the COX-2-I group (p = 0.003 and 0.122). The rate of hospitalization in the COX-2-I group was significantly lower than that of the control group (3.39% vs 13.06%, p = 0.003). No patient in the COX-2-I group required intensive care unit admission.

Long-term intermittent oral administration of selective COX-2-I in cirrhotic patients significantly reduces the occurrence of severe/critical COVID-19, acute decompensated events, and ACLF. It may also be used for systemic inflammation caused by other pathogens.

Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.

The ongoing COVID-19 pandemic has significantly impacted special populations, including immunocompromised individuals, people living with HIV (PLWHIV), pediatric patients, and those with chronic liver disease (CLD). This scoping review aims to map the clinical outcomes of these vulnerable groups when infected with various SARS-CoV-2 variants. The review identifies trends and patterns, noting that early variants, such as Alpha and Delta, are associated with more severe outcomes, including higher hospitalization and mortality rates. In contrast, the Omicron variant, despite its increased transmissibility, tends to cause milder clinical manifestations. The review highlights the necessity for ongoing surveillance and tailored healthcare interventions due to the heterogeneity of patient populations and the evolving nature of the virus. Continuous monitoring and adaptive healthcare strategies are essential to mitigate the impact of COVID-19 on these high-risk groups.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs fail to provide sufficient oxygen to the body's vital organs. It is commonly associated with COVID-19 patients. Severe cases of COVID-19 can lead to lung damage and organ failure due to an immune response in the body. To mitigate these effects, corticosteroids, which are known for their anti-inflammatory properties, have been suggested as a potential treatment option. The primary focus of this study was to assess the impact of various corticosteroid administration methods on the outcomes of patients with COVID-19. Methods: The current study was conducted on COVID-19 patients divided into three groups. The first group was administered 6 mg of intravenous (IV) dexamethasone; the second group received 1 mg/kg of IV methylprednisolone (methylprednisolone); and the third group received budesonide respirable solution at a dosage of 1mg twice daily. The neubilizer used was a vibrating mesh nebulizer (VMN). All patients received standard care. We found that dexamethasone administered intravenously led to a significant reduction in C-reactive protein levels, surpassing the effectiveness of both IV methylprednisolone and inhaled budesonide. Oxygen saturation without mask change over time showed statistically significant differences (p = 0.004) in favor of the budesonide and dexamethasone groups for all days. Individuals who received methylprednisolone showed a significant decrease in mortality rate and an extended survival duration, with statistical significance observed at p = 0.024. The rest of the parameters, including ferritin, lymphocytes, total leukocyte count, platelets, hemoglobin, urea, serum potassium, serum sodium, serum creatinine, serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, uric acid, albumin, globulin, erythrocyte sedimentation rate, international normalized ratio, oxygen saturation with flow, and oxygen flow, showed no statistically significant differences between the three drugs. In conclusion, treatment with IV methylprednisolone (1 mg/kg) resulted in a shorter hospital stay, decreased reliance on ventilation, and improved health outcomes for COVID-19 patients compared to using dexamethasone at a daily dosage of 6 mg or budesonide respirable solution at a dosage of 1mg twice daily.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Coronavirus disease 2019 (COVID-19) has been associated with liver injury incidence reported between 15% and 53%. Viral binding to ACE2 receptors in hepatobiliary cells is believed to cause liver inflammation. The relationship between hepatitis B and COVID-19 is poorly understood, but patients treated with immunosuppressive therapy for COVID-19 are at higher risk of hepatitis B reactivation (HBVr). We present a case of a patient with HBVr because of COVID-19, in the absence of any immunosuppressive treatment, leading to fulminant liver failure and subsequent requiring liver transplantation. Given low incidence, limited data, and no current guidelines, further studies are needed to evaluate the benefit and cost-effectiveness of anti-HBV prophylaxis in a patient with chronic hepatitis B (CHB) and COVID-19. Meanwhile, the American Association for the Study of Liver Diseases guidelines for patients with CHB and immunosuppressant use can be considered for anti-HBV prophylaxis for patients with CHB and COVID-19 to prevent HBVr on a case-by-case basis.

Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease.

Chronic liver disease presents a significant global health burden, characterized by several etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), chronic hepatitis B virus infection, and chronic hepatitis C virus infection. This review explored current epidemiological trends and projections for each etiology, looking into their respective burdens and challenges. MASLD, formerly known as nonalcoholic fatty liver disease, is the most prevalent cause of chronic liver disease, and its global incidence and prevalence are steadily rising. ALD, fueled by increased alcohol consumption, is also on the rise, with concerning implications for future mortality rates. Chronic hepatitis B and C infections remain major public health concerns, particularly in specific regions of the world, necessitating concerted efforts for screening and treatment. The coronavirus disease 2019 (COVID-19) pandemic has impacted the epidemiology of chronic liver disease, exacerbating mortality rates and disrupting healthcare services. Mental health issues arising from the pandemic further complicate the treatment of chronic liver disease, making comprehensive healthcare strategies essential. Despite advancements in treatment, chronic liver disease continues to impose a substantial economic burden, emphasizing the importance of preventive measures and early intervention. In conclusion, ongoing surveillance and research efforts are crucial for understanding and addressing the evolving landscape of chronic liver disease. Comprehensive strategies that encompass prevention, screening, and treatment of its different etiologies are essential for mitigating its impact and improving patient outcomes.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Specific associations between liver cirrhosis and liver transplant with poorer outcomes in COVID-19 are still not completely clear.

We aimed to evaluate the clinical characteristics and outcomes of patients with severe COVID-19 and cirrhosis or liver transplant in Sao Paulo, Brazil.

A retrospective observational study was conducted in a quaternary hospital. Patients with COVID-19 and liver cirrhosis or liver transplant were selected. The clinical and demographic characteristics, as well as the outcomes, were assessed using electronic records.

A total of 46 patients with COVID-19 and liver condition were included in the study. Patients with liver cirrhosis had significantly more endotracheal intubation and a higher relative risk of death than liver transplant recipients. Patients with higher MELD-Na scores had increased death rates and lower survival probability and survival time.

Patients with liver cirrhosis, especially those with higher MELD-Na scores, had poorer outcomes in COVID-19. Liver transplant recipients do not seem to be linked to poorer COVID-19 outcomes.

Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality.

A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves.

The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes.

There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

Coronavirus disease 2019 emerged in December 2019 and spread worldwide. This study aimed to clarify the impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan.

First, we collected the monthly numbers of HCC-related general medical practices from January 2019 to December 2021 at liver disease-specific medical institutions in Japan. Next, we collected individual clinical information from patients with newly diagnosed HCC during this period.

There was a decrease in the number of HCC-related medical practices, including referrals, enhanced abdominal ultrasonography and radiofrequency ablation, in Japan's first state of emergency (SOE; April-May 2020) compared with 2019. Fewer patients were diagnosed with new HCC during the first SOE than before or after it. There was no difference in tumor diameter, number of tumors or Barcelona Clinic Liver Cancer stage between patients diagnosed before the first SOE and those diagnosed during or after the first SOE. The median waiting times for treatment of patients diagnosed during and after the first SOE were 31 and 37 days, which were significantly shorter and not longer than that of patients diagnosed before the first SOE (36 days), respectively.

The number of HCC-related general medical practices decreased during the first SOE. However, the coronavirus disease 2019 pandemic did not lead to HCC progression by diagnostic delays or cause HCC treatment delays in Japan.

In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP).

This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023.

Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA).

On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations.