• COVID‐19 infection
• chronic liver disease
• liver dysfunction
• liver injury
• metabolic‐associated fatty liver disease

• COVID-19
• SARS-CoV-2
• alcohol
• alcohol-related liver disease
• cirrhosis
• liver

• Humans
• COVID-19/complications
• SARS-CoV-2
• Alcoholism/complications
• Alcoholism/epidemiology
• Liver Cirrhosis/etiology
• Liver Diseases, Alcoholic/complications
• Ethanol/adverse effects

• Bile acids
• COVID-19
• Liver damage
• Pregnancy
• SARS-CoV-2

• Humans
• Female
• Pregnancy
• COVID-19
• SARS-CoV-2
• Liver Diseases
• Liver
• Bile Acids and Salts

• covid-19
• incidence
• liver injury
• meta-analysis
• risk factors

• Humans
• Male
• COVID-19/complications
• SARS-CoV-2
• Liver Diseases/epidemiology
• Liver Diseases/etiology
• Liver Diseases/diagnosis
• Prognosis

• COVID-19
• Cytokine storm
• Direct hepatocyte injury
• Endotheliopathy
• Immuno-thromboinflammation
• Liver injury
• SARS-CoV-2

• Humans
• COVID-19/complications
• SARS-CoV-2
• RNA, Viral
• Endothelial Cells
• Incidence
• Chemical and Drug Induced Liver Injury, Chronic/complications
• Population Groups
• Liver Diseases
• Risk Factors
• Prognosis

Coronavirus disease 2019 (COVID-19) infection caused by the severe acute respiratory syndrome coronavirus 2 virus, its symptoms, treatment, and post-COVID-19 effects have been a major focus of research since 2020. In addition to respiratory symptoms, different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases, including liver abnormalities. The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients. The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers. Gut microbiota influences liver chemistry through its metabolites. Gut dysbiosis during COVID-19 treatment can promote liver inflammation. Here, we highlighted the bidirectional association of liver physiology and gut microbiota (gut-liver axis) and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.

• COVID-19
• Gut-liver axis
• Probiotics
• Prebiotics
• Cytokines
• Gut microbiome

• Humans
• Gastrointestinal Microbiome/physiology
• Probiotics/therapeutic use
• COVID-19 Drug Treatment
• COVID-19
• Liver Diseases/metabolism
• Inflammation
• Dysbiosis/therapy

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

• COVID-19
• Liver injury
• Cytokine storm
• Hypoxic hepatitis
• Drug-induced liver injury
• Chronic liver disease

• Humans
• COVID-19
• SARS-CoV-2
• Carcinoma, Hepatocellular
• Liver Neoplasms

• COVID-19 liver injury
• Perinatal liver disease
• Pregnancy
• Special populations
• Systemic inflammation

• Humans
• Pregnancy
• Female
• COVID-19/complications
• SARS-CoV-2
• Lung
• Liver

• hepatocytes
• liver

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.

Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.

During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.

• Aged
• COVID-19/complications
• Carcinoma, Hepatocellular
• Gastrointestinal Diseases
• Humans
• Liver/pathology
• Liver Neoplasms/pathology
• Pandemics
• SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2) and primary human hepatocytes. Pseudotyped viral particles expressing the full-length spike of SARS-CoV-2 and recombinant receptor binding domain (RBD) bind to ACE2 expressed by hepatocytes, promoting metabolic reprogramming towards glycolysis but also impaired mitochondrial activity. Human and hACE2 primary hepatocytes, where steatosis and inflammation were induced by methionine and choline deprivation, are more vulnerable to infection. Inhibition of the renin-angiotensin system increases the susceptibility of primary hepatocytes to infection with pseudotyped viral particles. Metformin, a common therapeutic option for hyperglycemia in type 2 diabetes patients known to partially attenuate fatty liver, reduces the infection of human and hACE2 hepatocytes. In summary, we provide evidence that hepatocytes are amenable to infection with SARS-CoV-2 pseudovirus, and we propose that metformin could be a therapeutic option to attenuate infection by SARS-CoV-2 in patients with fatty liver.

SARS-CoV-2 pseudovirus infects human hepatocytes leading to metabolic reprogramming towards glycolysis and impaired mitochondrial activity, and metformin can reduce infection under steatotic conditions.

Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8–3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.

• COVID-19
• DILI
• RUCAM
• Roussel Uclaf Causality Assessment Method
• drug-induced liver injury

• COVID-19
• Gastrointestinal manifestations
• Liver injury
• Liver transplantation
• SARS-CoV-2

Coronavirus disease 2019 (COVID-19) disease affects multiple organs, including anomalies in liver function. In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease. Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients, severity of liver injury, presence of comorbidity and pre-treatment. The method of antiviral treatment can also impact on liver function, which manifests as increasing values in liver function tests. Therefore, analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.

• COVID-19
• Pathogenesis of liver injury
• Angiotensin-converting enzyme 2 receptor
• Liver function tests
• Severe COVID-19
• Treatment effect

• Coronavirus disease 2019
• Critically ill patient
• Intensive care unit
• Liver biochemical parameters abnormalities
• Liver injury
• Mortality

• coronavirus disease 2019
• immunosuppression
• pediatric liver transplantation
• severe acute respiratory syndrome coronavirus 2
• viral hepatitis

Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.

• SARS-CoV-2
• COVID-19
• Liver injury
• Prognosis
• Treatment

• acute
• biochemistry
• coronavirus
• disease
• function
• infection
• injury
• liver
• mortality
• severity
• tests

• AOP
• COVID-19
• Liver
• Mechanism
• SARS-CoV-2

• Angiotensin-Converting Enzyme 2/antagonists & inhibitors
• Angiotensin-Converting Enzyme 2/metabolism
• Animals
• Antiviral Agents/adverse effects
• Antiviral Agents/therapeutic use
• COVID-19/complications
• COVID-19/metabolism
• Humans
• Inflammation/chemically induced
• Inflammation/etiology
• Inflammation/metabolism
• Liver/drug effects
• Liver/metabolism
• Liver Diseases/etiology
• Liver Diseases/metabolism
• SARS-CoV-2/drug effects
• SARS-CoV-2/metabolism
• COVID-19 Drug Treatment

Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The utility of laboratory hematology data in the diagnosis and risk stratification of patients with coronavirus disease 2019 (COVID-19) has not been comprehensively examined.

To address the following. (1) Are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in those patients with associated liver injury? (2) Is liver injury in COVID-19 a sign of severe disease and does liver injury correlate with hematologic markers of severe disease? And (3) What is the quality of this evidence?

To address these questions, a comprehensive systematic review was performed. We searched the peer reviewed medical literature using MEDLINE (PubMed interface), Web of Science, and EMBASE for cohort studies that specifically addressed liver injury and COVID-19 without limitation of date of publication or language. A quality assessment of the studies was performed using the Newcastle-Ottawa Scale.

Thirty-two articles were suitable for inclusion in our systematic review. These included 22 articles with a cohort of COVID-19 patients with liver injury, 5 comparing non-severe vs severe COVID-19 populations in which liver injury was addressed, and 5 other cohort studies with a focus on liver injury. White blood cell count, absolute neutrophil count, absolute lymphocyte count (ALC), and hemoglobin were the parameters most helpful in distinguishing COVID-19 with liver injury from COVID-19 without liver injury. ALC and d-dimer were identified as being potentially useful in distinguishing non-severe from severe COVID-19. Liver injury was more frequently seen in cohorts with severe disease. Most studies were of high quality (24/48, 86%) with 4/28 (14%) of moderate quality and 0 of low quality.

Our study supports the use of select hematologic parameters in diagnosis and risk stratification of liver injury in COVID-19 patients. Although of overall high quality, the current medical literature is limited by the small number of studies with high statistical power and the variable definition of COVID-19 liver injury in the literature.

• COVID-19
• SARS-CoV-2
• Laboratory hematology
• Systematic review
• Coagulation
• Liver injury

Objective: This study was intended to investigate the relationship between COVID-19 disease and ovarian function in reproductive-aged women.

Methods: Female COVID-19 patients of reproductive age were recruited between January 28 and March 8, 2020 from Tongji Hospital in Wuhan. Their baseline and clinical characteristics, as well as menstrual conditions, were recorded. Differentials in ovarian reserve markers and sex hormones (including anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], the ratio of FSH to luteinizing hormone [LH], estradiol [E2], progesterone [P], testosterone [T], and prolactin [PRL] were compared to those of healthy women who were randomly selected and individually matched for age, region, and menstrual status. Uni- and multi-variable hierarchical linear regression analyses were performed to identify risk factors associated with ovarian function in COVID-19 women.

Results: Seventy eight patients agreed to be tested for serum hormone, of whom 17 (21.79%) were diagnosed as the severe group and 39 (50%) were in the basal level group. Menstrual status (P = 0.55), menstrual volumes (P = 0.066), phase of menstrual cycle (P = 0.58), and dysmenorrhea history (P = 0.12) were similar without significant differences between non-severe and severe COVID-19 women. Significant lower serum AMH level/proportion (0.19/0.28 vs. 1.12 ng/ml, P = 0.003/0.027; AMH ≤ 1.1 ng/ml: 75/70.4 vs. 49.7%, P = 0.009/0.004), higher serum T (0.38/0.39 vs. 0.22 ng/ml, P < 0.001/0.001) and PRL (25.43/24.10 vs. 12.12 ng/ml, P < 0.001/0.001) levels were observed in basal level and the all-COVID-19 group compared with healthy age-matched control. When adjusted for age, menstrual status and parity variations in multivariate hierarchical linear regression analysis, COVID-19 disease was significantly associated with serum AMH (β = −0.191; 95% CI: −1.177–0.327; P = 0.001), T (β = 0.411; 95% CI: 11.154–22.709; P < 0.001), and PRL (β = 0.497; 95% CI: 10.787–20.266; P < 0.001), suggesting an independent risk factor for ovarian function, which accounted for 3.2% of the decline in AMH, 14.3% of the increase in T, and 20.7% of the increase in PRL.

Conclusion: Ovarian injury, including declined ovarian reserve and reproductive endocrine disorder, can be observed in women with COVID-19. More attention should be paid to their ovarian function under this pandemic, especially regarding reproductive-aged women.

Clinical Trial Number: ChiCTR2000030015.

• COVID-19
• infectious disease
• observational study
• ovarian injury
• ovarian reserve
• reproductive health
• sex hormones