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1.
Impact of Liver and Pancreas Diseases on Nutritional Status.
Cañamares-Orbis, P, Bernal-Monterde, V, Sierra-Gabarda, O, Casas-Deza, D, Garcia-Rayado, G, Cortes, L, Lué, A
Nutrients. 2021;(5)
Abstract
Liver and pancreatic diseases have significant consequences on nutritional status, with direct effects on clinical outcomes, survival, and quality of life. Maintaining and preserving an adequate nutritional status is crucial and should be one of the goals of patients with liver or pancreatic disease. Thus, the nutritional status of such patients should be systematically assessed at follow-up. Recently, great progress has been made in this direction, and the relevant pathophysiological mechanisms have been better established. While the spectrum of these diseases is wide, and the mechanisms of the onset of malnutrition are numerous and interrelated, clinical and nutritional manifestations are common. The main consequences include an impaired dietary intake, altered macro and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, and osteopathy. In this review, we summarize the factors contributing to malnutrition, and the effects on nutritional status and clinical outcomes of liver and pancreatic diseases. We explain the current knowledge on how to assess malnutrition and the efficacy of nutritional interventions in these settings.
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2.
Effect of Moderate Hepatic Impairment on the Pharmacokinetics of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor.
Chavan, A, Burke, L, Sawant, R, Navarro-Gonzales, P, Vargo, D, Paulson, SK
Clinical pharmacology in drug development. 2021;(8):950-958
Abstract
Vadadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor in development for the treatment of anemia of chronic kidney disease. This phase 1, open-label, parallel-group, single-dose study evaluated the pharmacokinetics of 450-mg vadadustat in adults with moderate hepatic impairment (Child-Pugh class B) vs those with normal hepatic function. Primary end points were area under the plasma concentration-time curve (AUC) from dosing to last concentration and to infinity, as well as maximum concentration (Cmax ); additional pharmacokinetic parameters included time to Cmax (Tmax ) and half-life. Safety and tolerability were also assessed. All enrolled participants (n = 16) completed the study. Demographics were similar in both groups (overall, 100% White; 62.5% female; mean age, 59.2 years). Vadadustat plasma exposure was higher in the moderate hepatic impairment group, whereas maximum concentration was similar between groups. Point estimates of the hepatic impairment : normal geometric mean ratios (90% confidence interval) for AUC from dosing to last concentration, AUC from dosing to infinity, and Cmax were 1.05 (0.82-1.35), 1.06 (0.82-1.36), and 1.02 (0.79-1.32), respectively. Mean elimination half-life was 5.8 and 7.8 hours in the normal and hepatic impairment groups, respectively. Treatment-emergent adverse events were mostly mild in severity, and vadadustat was generally well tolerated. In conclusion, moderate hepatic impairment did not significantly impact vadadustat systemic exposure, and mild hepatic impairment is unlikely to alter vadadustat exposure.
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Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.
Cifuentes, LI, Gattini, D, Torres-Robles, R, Gana, JC
The Cochrane database of systematic reviews. 2021;(1):CD011973
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Abstract
BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein thrombosis. Therefore, prevention is important. Band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding in children. However, primary prophylaxis is not the current standard of care in paediatric patients because it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES To determine the benefits and harms of beta-blockers compared with placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (April 2020). We screened the reference lists of the retrieved publications and manually searched the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstract books from 2008 to December 2019. We searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA We planned to include randomised clinical trials, irrespective of blinding, language, or publication status to assess benefits and harms. We included observational studies, retrieved with the searches for randomised clinical trials, for a narrative report of harm. DATA COLLECTION AND ANALYSIS We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to asses risk of bias and use GRADE to assess the certainty of evidence. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and health-related quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to use intention-to-treat principle. We planned to analyse data with RevMan Analysis. MAIN RESULTS We found no randomised clinical trials that assessed beta-blockers compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We found four observational studies that reported on harms. As a systematic search for observational studies was not planned, we only listed the reported harms in a table. AUTHORS' CONCLUSIONS Randomised clinical trials assessing the benefits or harms of beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of beta-blockers versus placebo on patient-relevant clinical outcomes, such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.
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4.
Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.
Cifuentes, LI, Gattini, D, Torres-Robles, R, Gana, JC
The Cochrane database of systematic reviews. 2021;(1):CD011561
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Abstract
BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children and adolescents with chronic liver disease or portal vein thrombosis. Prevention is, therefore, important. Randomised clinical trials have shown that non-selective beta-blockers and endoscopic variceal band ligation decrease the incidence of variceal bleeding in adults. In children and adolescents, band ligation, beta-blockers, and sclerotherapy have been proposed as primary prophylaxis alternatives for oesophageal variceal bleeding. However, it is unknown whether these interventions are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES To assess the benefits and harms of band ligation compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, and two other databases (April 2020). We scrutinised the reference lists of the retrieved publications, and we also handsearched abstract books of the two main paediatric gastroenterology and hepatology conferences from January 2008 to December 2019. We also searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA We aimed to include randomised clinical trials irrespective of blinding, language, or publication status, to assess the benefits and harms of band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. If the search for randomised clinical trials retrieved quasi-randomised and other observational studies, then we read them through to extract information on harm. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology to perform this systematic review. We used GRADE to assess the certainty of evidence for each outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We used the intention-to-treat principle. We analysed data using Review Manager 5. MAIN RESULTS One conference abstract, describing a feasibility multi-centre randomised clinical trial, fulfilled our review inclusion criteria. We judged the trial at overall high risk of bias. This trial was conducted in three hospital centres in the United Kingdom. The aim of the trial was to determine the feasibility and safety of further larger randomised clinical trials of prophylactic band ligation versus no active treatment in children with portal hypertension and large oesophageal varices. Twelve children received prophylactic band ligation and 10 children received no active treatment. There was no information on the age of the children included, or about the diagnosis of any child included. All children were followed up for at least six months. Mortality was 8% (1/12) in the band ligation group versus 0% (0/10) in the no active intervention group (risk ratio (RR) 2.54, 95% confidence interval (CI) 0.11 to 56.25; very low certainty of evidence). The abstract did not report when the death occurred, but we assume it happened between the six-month follow-up and one year. No child (0%) in the band ligation group developed adverse events (RR 0.28, 95% CI 0.01 to 6.25; very low certainty of evidence) but one child out of 10 (10%) in the no active intervention group developed idiopathic thrombocytopaenic purpura. One child out of 12 (8%) in the band ligation group underwent liver transplantation versus none in the no active intervention group (0%) (RR 2.54, 95% CI 0.11 to 56.25; very low certainty of evidence). The trial reported no other serious adverse events or liver-related morbidity. Quality of life was not reported. Oesophageal variceal bleeding occurred in 8% (1/12) of the children in the band ligation group versus 30% (3/10) of the children in the no active intervention group (RR 0.28, 95% CI 0.03 to 2.27; very low certainty of evidence). No adverse events considered non-serious were reported. Two children were lost to follow-up by one-year. Ten children in total completed the trial at two-year follow-up. There was no information on funding. We found two observational studies on endoscopic variceal ligation when searching for randomised trials. One found no harm, and the other reported E nterobacter cloacae septicaemia in one child and mild, transient, upper oesophageal sphincter stenosis in another. We did not assess these studies for risk of bias. We did not find any ongoing randomised clinical trials of interest to our review. AUTHORS' CONCLUSIONS The evidence, obtained from only one feasibility randomised clinical trial at high risk of bias, is very scanty. It is very uncertain about whether prophylactic band ligation versus sham or no (active) intervention may affect mortality, serious adverse events and liver-related morbidity, or oesophageal variceal bleeding in children and adolescents with portal hypertension and large oesophageal varices. We have no data on quality of life. No adverse events considered non-serious were reported. The results presented in the trial need to be interpreted with caution. In addition, the highly limited data cover only part of our research question; namely, children with portal hypertension and large oesophageal varices. Data on children with portal vein thrombosis are lacking. Larger randomised clinical trials assessing the benefits and harms of band ligation compared with sham treatment for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, quality of life, failure to control bleeding, and adverse events.
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5.
Diagnostic Accuracy of Biomarkers of Alcohol Use in Patients With Liver Disease: A Systematic Review.
Arnts, J, Vanlerberghe, BTK, Roozen, S, Crunelle, CL, Masclee, AAM, Olde-Damink, SWM, Heeren, RMA, van Nuijs, A, Neels, H, Nevens, F, et al
Alcoholism, clinical and experimental research. 2021;(1):25-37
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Abstract
BACKGROUND AND AIMS Alcohol-related liver disease is the most frequent cause of cirrhosis and a major indication for liver transplantation. Several alcohol use biomarkers have been developed in recent years and are already in use in several centers. However, in patients with liver disease their diagnostic performance might be influenced by altered biomarker formation by hepatic damage, altered excretion by kidney dysfunction and diuretics use, and altered deposition in hair and nails. We systematically reviewed studies on the diagnostic accuracy of biomarkers of alcohol use in patients with liver disease and performed a detailed study quality assessment. METHODS A structured search in PubMed/Medline/Embase databases was performed for relevant studies, published until April 28, 2019. The risk of bias and applicability concerns was assessed according to the adapted quality assessment of diagnostic accuracy studies-2 (QUADAS-2) checklist. RESULTS Twelve out of 6,449 studies met inclusion criteria. Urinary ethyl glucuronide and urinary ethyl sulfate showed high sensitivity (70 to 89 and 73 to 82%, respectively) and specificity (93 to 99 and 86 to 89%, respectively) for assessing any amount of alcohol use in the past days. Serum carbohydrate-deficient transferrin showed low sensitivity but higher specificity (40 to 79 and 57 to 99%, respectively) to detect excessive alcohol use in the past weeks. Whole blood phosphatidylethanol showed high sensitivity and specificity (73 to 100 and 90 to 96%, respectively) to detect any amount of alcohol use in the previous weeks. Scalp hair ethyl glucuronide showed high sensitivity (85 to 100%) and specificity (97 to 100%) for detecting chronic excessive alcohol use in the past 3 to 6 months. Main limitations of the current evidence are the lack of an absolute gold standard to assess alcohol use, heterogeneous study populations, and the paucity of studies. CONCLUSIONS Urinary and scalp hair ethyl glucuronide are currently the most validated alcohol use biomarkers in patients with liver disease with good diagnostic accuracies. Phosphatidylethanol is a highly promising alcohol use biomarker, but so far less validated in liver patients. Alcohol use biomarkers can complement each other regarding diagnostic time window. More validation studies on alcohol use biomarkers in patients with liver disease are needed.
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The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks.
Rosas-Rodríguez, JA, Valenzuela-Soto, EM
Life sciences. 2021;:119943
Abstract
Glycine betaine (N, N, N-trimethyl amine) is an osmolyte accumulated in cells that is key for cell volume and turgor regulation, is the principal methyl donor in the methionine cycle and is a DNA and proteins stabilizer. In humans, glycine betaine is synthesized from choline and can be obtained from some foods. Glycine betaine (GB) roles are illustrated in chemical, metabolic, agriculture, and clinical medical studies due to its chemical and physiological properties. Several studies have extensively described GB role and accumulation related to specific pathologies, focusing mainly on analyzing its positive and negative role in these pathologies. However, it is necessary to explain the relationship between glycine betaine and different pathologies concerning its role as an antioxidant, ability to methylate DNA, interact with transcription factors and cell receptors, and participate in the control of homocysteine concentration in liver, kidney and brain. This review summarizes the most important findings and integrates GB role in neurodegenerative, cardiovascular, hepatic, and renal diseases. Furthermore, we discuss GB impact on other dysfunctions as inflammation, oxidative stress, and glucose metabolism, to understand their cross-talks and provide reliable data to establish a base for further investigations.
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Band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.
Gana, JC, Cifuentes, LI, Gattini, D, Torres-Robles, R
The Cochrane database of systematic reviews. 2020;(11):CD011803
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Abstract
BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. In adults, numerous randomised clinical trials have demonstrated benefits of non-selective beta-blockers and endoscopic variceal ligation as primary prevention in decreasing the risk of variceal haemorrhage. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, primary prophylaxis is not the current standard of care in children because it is unknown whether those treatments are of benefit or cause harm when used for primary prophylaxis of oesophageal variceal bleeding in children and adolescents. OBJECTIVES To determine the benefits and harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (27 April 2020). We scrutinised the reference lists of retrieved publications, and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from 2008 to 2019. We searched ClinicalTrials.gov, FDA, EMA, and WHO for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA We planned to include randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. If the search for randomised clinical trials retrieved quasi-randomised and observational studies, then we read them through to extract information on harms. DATA COLLECTION AND ANALYSIS We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to assess risk of bias and use GRADE to assess the certainty of evidence per outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to analyse data with intention-to-treat. We planned to use Review Manager 5 to analyse the data. MAIN RESULTS We found no randomised clinical trials assessing band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. AUTHORS' CONCLUSIONS Randomised clinical trials assessing the benefits or harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of band ligation versus sclerotherapy on patient-relevant clinical outcomes such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of these two interventions.
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Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review.
Fu, Y, Zhu, W, Zhou, Y, Chen, H, Yan, L, He, W
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(2):139-147
Abstract
BACKGROUND The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population. METHODS We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66-0.93), major bleeding (RR 0.68, 95% CI 0.53-0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41-0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57-1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61-1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37-0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38-0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.97) compared with warfarin. CONCLUSIONS Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.
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The effect of vitamin D supplementation on the progression of fibrosis in patients with chronic liver disease: A protocol for a systematic review and meta-analysis.
Chen, T, Zuo, X, Wang, S, Yu, P, Yuan, J, Wei, S, Chen, J, Sun, Y, Gao, Y, Li, X
Medicine. 2020;(19):e20296
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Abstract
BACKGROUND Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD. METHODS The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3. RESULTS This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD. CONCLUSION This study determines the positive efficacy of VD supplementation for CLD. ETHICS AND DISSEMINATION This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals. REGISTRATION NUMBER INPLASY202040054.
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10.
Direct or Collateral Liver Damage in SARS-CoV-2-Infected Patients.
Lizardo-Thiebaud, MJ, Cervantes-Alvarez, E, Limon-de la Rosa, N, Tejeda-Dominguez, F, Palacios-Jimenez, M, Méndez-Guerrero, O, Delaye-Martinez, M, Rodriguez-Alvarez, F, Romero-Morales, B, Liu, WH, et al
Seminars in liver disease. 2020;(3):321-330
Abstract
Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.