Is Fatty Liver Associated with Increased Mortality and Morbidity in Coronavirus Disease 2019 (COVID-19) Pneumonia?

Background: Fatty liver has been shown to be associated with severe COVID-19 disease without any impact on mortality. This is based on heterogenous criteria for defining both fatty liver as well as the severity parameters. This study aimed to study the impact of fatty liver on the mortality and severity of disease in patients with COVID-19 pneumonia. Methods: In a case control study design, patients with COVID-19 pneumonia (COVID-19 computed tomography severity index [CTSI] on high-resolution computed tomography chest of ≥1) with fatty liver (defined as liver to spleen attenuation index ≤5 on noncontrast computed tomography cuts of upper abdomen) were compared with those without fatty liver. The primary outcome measure was in-hospital mortality, and the secondary outcome measures were CTSI score, need for intensive care unit (ICU) care, need for ventilatory support, duration of ICU stay, and duration of hospital stay. Results: Of 446 patients with COVID-19 pneumonia, 289 (64.7%)admitted to Max Hospital, Saket, India, between January 1, 2021, and October 30, 2021, had fatty liver. Fifty-nine of 446 patients died during the index admission. In-hospital mortality was not different between patients with fatty liver (38 [13.24%]) or without fatty liver (21 [13.81%]). COVID-19 CTSI score was found to be significantly higher among patients who had fatty liver (13.40 [5.16] vs 11.81 [5.50]; P = 0.003). There was no difference in the requirement of ICU (94 [32%] vs 62 [39.49%]; P = 0.752), requirement of ventilatory support (27 [9.34%] vs 14 [8.91%]; P = 0.385), duration of ICU stay (8.29 [6.87] vs 7.07 [5.71] days; P = 0.208), and duration of hospital stay (10.10 [7.14] vs 10.69 [8.13] days; P = 0.430) between the groups with fatty liver or no fatty liver. Similarly, no difference was found in primary or secondary outcomes measure between the group with severe fatty liver vs mild/moderate or no fatty liver. High total leucocyte count and Fibrosis-4 (FIB-4) index were independently associated with mortality. Conclusions: Fatty liver may not be associated with increased mortality or clinical morbidity in patients who have COVID-19 pneumonia.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-Analysis

BACKGROUND: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. METHODS: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. FINDINGS: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). INTERPRETATION: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission;and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.

Effect of COVID-19 on Pre-existing Liver disease: What Hepatologist Should Know?

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Advanced age, hypertension, diabetes, obesity, malignancy, and cardiovascular disease predispose them to severe disease and the need for hospitalization. Data on pre-existing liver disease in patients with COVID-19 is limited, and most studies had only 3-8% of these patients. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-6 fold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. Few case reports had shown SARS-CoV-2 as an acute event in the decompensation of underlying chronic liver disease. Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir is found to be safe in limited studies in a patient with cirrhosis and COVID-19. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic will have severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis.

BACKGROUND: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored. OBJECTIVES: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course. METHODS: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome. RESULTS: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3). CONCLUSIONS: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-Analysis.

BACKGROUND: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. METHODS: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. FINDINGS: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). INTERPRETATION: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.