The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.

A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group. Additionally, 34 age-, gender-, etiology-, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score-matched ACLF patients were screened from 286 ACLF patients as the ACLF group. From 382 COVID-19 patients, 34 were selected as the COVID-19 group, matching the ACLF+COVID-19 group in age, gender, and illness severity. Clinical features of these three groups were compared, with the primary measure being the 28-day mortality rate in the ACLF patients and the secondary measures including clinical symptoms, laboratory tests, comorbidities, and complications in three groups.

Compared with the ACLF group, the ACLF+COVID-19 group had significantly higher incidence rates of fever, cough, sputum production, fatigue, and hypoxemia (all p<0.01). Patients in the ACLF+COVID-19 group were more likely to have hepatic encephalopathy (p=0.015), lower platelet count (p=0.016) and elevated IL-6 level (p=0.026), and higher MELD-Na score (p=0.041) one week after admission, but without a significant increase in 28-day mortality rate (p=0.16).

ACLF patients with COVID-19 have increased risk for thrombocytopenia, more obvious inflammatory response, and rapid disease progression 1 week after admission, but the 28-day mortality rate is similar to that of ACLF patients without COVID-19.

SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown.

Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated.

The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination.

The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.

Inactivated SARS-CoV-2 vaccination has recently been approved for children aged 3-17 years in China. However, data on long-term humoral responses to inactivated vaccines in children with chronic hepatitis B (CHB) are still limited.

In this prospective observational study, CHB children after primary inactivated SARS-CoV-2 vaccines were recruited consecutively and followed up for 1 year. CHB adults from another cohort study (NCT05007665) were used as a control. The receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibody (NAb), neutralization against Omicron (BA2.12.1, BA.4 and BA.5), and memory B -cell (MBC) responses were evaluated.

Overall, 115 CHB children and 351 CHB adults were included in this analysis. The antibody titers decreased over the first ~180 days and then plateaued up to 1 year in CHB children. However, lower and faster declines in antibody responses were observed in CHB adults. Interestingly, the seroprevalence of antibodies was still high after over 8 months in CHB children (anti-RBD-IgG [90%] and NAbs [83%]). However, neutralization against Omicron subvariants was significantly reduced in CHB children (-3.68-fold to -8.60-fold). Notably, neutralization against the BA.5 subvariant was obviously diminished in CHB children compared with adults. Moreover, CHB children had similar RBD-specific MBCs but higher RBD-specific atypical MBCs compared with adults.

Inactivated vaccination could elicit more robust and durable antibody responses to the wild-type SARS-CoV-2 strain in CHB children than in CHB adults but showed inferior responses to Omicron subvariants (especially to the BA.5 strain). Hence, new Omicron-related or all-in-one vaccines are needed immediately for CHB children.

As of June 2022, more than 530 million people worldwide have become ill with coronavirus disease 2019 (COVID-19). Although COVID-19 is most commonly associated with respiratory distress (severe acute respiratory syndrome), meta-analysis have indicated that liver dysfunction also occurs in patients with severe symptoms. Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensin-converting enzyme receptors. It has also been reported that in some patients with COVID-19, therapeutic strategies, including repurposed drugs (mitifovir, lopinavir/ritonavir, tocilizumab, etc.) triggered liver injury and cholestatic toxicity. Several proven indicators support cytokine storm-induced hepatic damage. Because there are 1.5 billion patients with chronic liver disease worldwide, it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics. This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

People across the world are affected by the "coronavirus disease 2019 (COVID-19)", brought on by the "SARS-CoV type-2 coronavirus". Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndrome's hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.

As the third year of the SARS-CoV-2 pandemic approaches, COVID-19 continues to cause substantial morbidity and mortality due to waning vaccine efficacy and the emergence of new, highly contagious subvariants and better therapies are urgently needed.

Hospitalized patients who develop hypoxia due to SARS-CoV-2 infection are typically treated with an antiviral agent, remdesivir, as well as an immunomodulator, dexamethasone, but mortality rates for severe COVID-19 remain unacceptably high. Mounting evidence suggests a second immunomodulator added to the standard of care may benefit some hospitalized patients; however, the optimal treatment remains controversial.

On 2 June 2022, the United States National Institutes of Health reported results from a large, randomized placebo-controlled clinical trial known as ACTIV-1. The study found a mortality benefit and substantially improved clinical status for adults hospitalized with COVID-19 who were treated with infliximab, a chimeric monoclonal antibody that binds to and inhibits TNF-α, and is widely used to treat a variety of autoimmune conditions, including rheumatoid arthritis, Crohn's disease, and ulcerative colitis. This manuscript reviews what is known about infliximab as an immunomodulator for patients with COVID-19 and explores how this agent may be used in the future to address the SARS-CoV-2 pandemic.

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg⁹-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg⁹-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg⁹-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg⁹-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.

SARS-CoV-2 is a novel coronavirus that expanded worldwide, generating a pandemic of acute respiratory syndrome called "coronavirus disease 2019" (COVID-19), which resulted in a global health crisis. The spectrum of COVID-19 manifestations ranges from none or mild symptoms to severe respiratory failure associated with systemic manifestations, mostly gastrointestinal symptoms. Hypercoagulability is an important feature of COVID-19 disease, which can potentially influence patients' prognosis. Therefore, gastroenterologists should focus on subjects with concomitant hypercoagulable gastrointestinal disorders as they may display a higher risk of thrombotic complications during SARS-CoV-2 infection. The aim of this review is to summarize the available evidence regarding the interplay of the prothrombotic pathogenetic mechanisms of both COVID-19 and hypercoagulable digestive diseases and the possible clinical implications. We summarized the potential interplay of prothrombotic mechanisms of both COVID-19 and hypercoagulable digestive diseases in the graphical abstract.

The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

The incidence of nonalcoholic fatty liver disease (NAFLD) has seen a steep rise in parallel with the global obesity and metabolic syndrome epidemic. The presence of NAFLD contributes to significant socioeconomic burden due to healthcare costs, progression of liver disease as non-alcoholic steatohepatitis (NASH), and later cirrhosis and hepatocellular carcinoma (HCC). With the advent of widely available imaging, it is also being detected as an incidental diagnosis in individuals with systemic disease like metabolic syndrome, diabetes, chronic cardiac disease, polycystic ovarian syndrome, etc. or in asymptomatic persons on presurgical evaluation or even annual health assessments. Gastroenterologists, hepatologists, physicians and surgeons need to be updated about the new diagnostic criteria of Metabolic (dysfunction)-associated fatty liver disease, noninvasive tests (NITs) of liver fibrosis, new tools of elastography, and identification of those with high-risk disease. In this review, we appraise the relevance of new diagnostic definitions, steatosis and fibrosis estimation tests, advanced imaging like magnetic resonance elastography and proton density fat fraction and discuss the diagnostic algorithm for incidentally detected NAFLD.

Mishra S, Bhujade H, Butt AS, et al. Work-up for Incidentally Detected NAFLD: How Far is It Worth? Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S26-S36.

Fever and cough are the most common clinical symptoms of coronavirus disease 2019 (COVID-19), but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in people with additional comorbidities. COVID-19 may be a new cause of liver disease, as liver profile disturbance is one of the most common findings among patients. The molecular mechanism underlying this phenomenon, however, is still unknown. In this paper, we review the most current research on the patterns of change in liver profile among patients with COVID-19, the possible explanation for these findings, and the relation to pre-existing liver disease in these patients.

About 20% of patients infected with SARS-CoV-2 develop COVID-19-the disease that has dominated health care in the last two years. The course of COVID-19 in patients with advanced liver disease tends to be severe, patients also suffer from a higher risk of complications and death. The primary object of this study was to assess the risk and causes of death in patients with cirrhosis and hepatocellular carcinoma (HCC).

From a group of 4,314 patients hospitalized at Jerzy Gromkowski Regional Specialist Hospital in Wroclaw (Poland) due to SARS-CoV-2/COVID-19 infection between March 15, 2020, and January 31, 2022, we selected a cohort of 31 patients with liver cirrhosis (12 women and 19 men) and 7 patients with HCC developed on the cirrhotic liver (1 woman, 6 men). The control group included 123 patients without liver disease. In the entire cohort, we analyzed the course of COVID-19 infection, baseline oxygen demand, liver function (assessed using the CTP-Child-Turoctte-Pugh score and MELD-Model of End-Stage Liver Disease scales), length of hospitalization, development of acute-on-chronic liver failure, and deaths.

The mean age of the patients was 56.6 years in the liver cirrhosis group, 63.3 years for patients with (HCC) hepatocellular carcinoma, and 64 years in the control group. Time of hospitalization averaged 15.52 days and 11.14 days for patients with liver cirrhosis and liver cancer, respectively. For the control group, the average duration of the hospital stay was 11.61 days. With respect to baseline liver function assessed using the CTP score, in the cirrhosis group 10 patients were CTP class A, 19 patients were class B and 9 patients were class C. The cancer group included 3 patients with class A, 2 patients with class B, and 2 patients with class C. In the studied cohort, 22 patients had a baseline MELD score < 12 points, and in 15 patients was > 12. In the HCC group, it was, respectively, CTP A:3, B: 2, C: 2, and MELD < 12: 3, ≥12: 4 people. Most of these patients presented with a progression of liver disease. Fifteen patients died, including 12 with cirrhosis and 3 with HCC, accounting for 39.47% in the entire cohort, 39% in the cirrhotic group and 43% in the HCC group, and 13 in the control group (10.6%), There was a clear statistical difference between the mortality rate in the group with liver disease and in the control group.

Infection with SARS-CoV-2/COVID-19 in patients with cirrhosis and HCC tends to have a more severe course and leads to exacerbation of the liver disease. The most common cause of death in the analyzed cohort infected with SARS-CoV-2/COVID-19 was the progression of liver disease, complicated by liver failure.

The association between alcohol and liver disease, including alcoholic hepatitis, cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, has been well described, but the same cannot be said for the association between smoking, water pipe or tobacco chewing. A review of cumulative evidence suggests that smoking is independently a risk factor for liver fibrosis and contributes to carcinogenesis in HCC. Smoking-related fibrosis has been reported in patients with nonalcoholic fatty liver disease, primary biliary cholangitis, alcoholic liver disease and chronic viral hepatitis. Heavy smoking leads to systemic inflammation, oxidative stress, insulin resistance, and results in tissue hypoxia, as well as free radical damage. Other than damaging the liver, patients also suffer from the systemic effects of the 4000 chemicals associated with tobacco, which include nitrosamines, aromatic hydrocarbons, nicotine, nornicotine, and other alkaloids. These include respiratory ailments, cancer of the lungs, oral cavity, esophagus, pancreas and colon, atherosclerotic vascular disease, and stroke.