Liver injury in COVID-19 patients with non-alcoholic fatty liver disease: an update.

The coronavirus disease 2019 (COVID-19) pandemic has revolutionized the priorities of the medical society worldwide. Although most patients infected with SARS-CoV-2 exhibit respiratory symptoms, other organs may also be involved, including the liver, often resulting in liver injury. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its prevalence is expected to increase together with the epidemics of type 2 diabetes and obesity. Data about liver injury during COVID-19 are numerous, while overviews of this infection in patients with NAFLD, both in terms of respiratory and liver, are emerging. In this review, we summarise the current research focusing on COVID-19 in NAFLD patients and discuss the association between liver injury in COVID-19 subjects and non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease and non-liver comorbidities.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

Trends of Cirrhosis-related Mortality in the USA during the COVID-19 Pandemic.

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0-1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9-8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3-12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3-7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.

Nonalcoholic fatty liver disease and diabetes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.

The Impact of Nonalcoholic Fatty Liver Disease on Severe Community-Acquired Pneumonia Outcomes.

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality, while nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD is associated with systemic changes in immune response, possibly linked to CAP severity. However, the impact of NAFLD on CAP outcomes has not been determined. The aim of this study was to evaluate clinical course, complications and outcomes of severe CAP requiring ICU treatment in patients with NAFLD in the pre-COVID-19 era. A retrospective cohort study included 138 consecutively hospitalized adult patients with severe CAP admitted to the ICU during a 4-year period: 80 patients with NAFLD and 58 controls. Patients with NAFLD more frequently presented with ARDS (68.7% vs. 43.1%), and required invasive mechanical ventilation (86.2% vs. 63.8%), respiratory ECMO (50% vs. 24.1%), and continuous renal replacement therapy (62.5% vs. 29.3%). Mortality was significantly higher in the NAFLD group (50% vs. 20.7%), and the time from hospital admission to death was significantly shorter. In survival analysis, NAFLD (HR 2.21, 95%CI 1.03-5.06) was associated with mortality independently of other components of metabolic syndrome. In conclusion, our study identified NAFLD as an independent predictor of mortality in patients with severe CAP.

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States.

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BACKGROUND: The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the U.S, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Vital Statistic System from the CDC WONDER platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modeling analysis. RESULTS: Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardized mortality rates (ASMR) for ALD dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 3.5% to 17.6%, P<0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs.13.04) and 2021 (17.42 vs.13.41). ASMR for NAFLD also increased during the pandemic (APC:14.5%), while the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all P<0.05), with similar but less critical findings for NAFLD while rates were steady for non-Hispanic Asians throughout 2010-2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25-44 age group (APC: 34.6%, versus 13.7% and 12.6% for 45-64 and ≥65, all P<0.01), which were also all higher than pre-COVID-19 rates (all P<0.01). CONCLUSIONS: ASMR for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. LAY SUMMARY: The impact of the pandemic on people with liver disease in the U.S remains unclear. This study indicated that age-standardized mortality rates for alcohol associated liver disease and non-alcohol fatty liver disease greatly accelerated during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. Increasing awareness about the care importance of chronic liver disease in specific populations must be prioritized.

A Multidisciplinary Approach and Current Perspective of Nonalcoholic Fatty Liver Disease: A Systematic Review.

In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.

Global burden of nonalcoholic steatohepatitis-related liver cancer, 1990-2019: a systematic analysis for the GBD 2019.

With the pandemic of metabolic diseases, nonalcoholic fatty liver disease (NAFLD) prevalence has dramatically elevated. NAFLD encompasses a spectrum of diseases including simple steatosis and nonalcoholic steatohepatitis (NASH), which can further progress to cirrhosis or liver cancer (LC). However, data are lacking on the burden and trend of NASH-related LC. Here, we analyzed the trends and changes of NASH-related LC burden using Global Burden of Disease (GBD) data (1990-2019). In 2019, the global incidence, prevalence, disability-adjusted life years (DALYs) and deaths of NASH related LC were 36.3 thousand (95% UI 29.5-44.9), 46.8 thousand (38.2-57.6), 796 thousand (657-976) and 34.7 thousand (28.4-43.2), respectively. The absolute numbers and rates of NASH-related LC incidence, mortality, and DALY significantly elevated from 1990 to 2019. With the age increased, the incidences, DALYs and deaths of NASH-related LC significantly elevated. The incidence and mortality rate of NASH-related LC significantly increased from 2010 to 2019 in individuals aged from 20 to 54 and older than 55 years old. We also found that a large disparity of NASH-related LC burden in different socio-demographic index (SDI) locations. The crude number and the age-standardized rate of incidences, DALYs and deaths was highest in the middle SDI locations and high SDI locations showed the largest increase of NASH-related LC burden from 1990 to 2019. Moreover, the proportion of LC incidences, deaths and DALYs attributed to NASH were 4.74%, 5.30% and 4.25%, respectively in 1990 which were increased by 43.5%, 35.3% and 49.4%, respectively in 2019. Conclusion: The global burden of NASH-related LC and the proportion LC burden attributed to NASH are significantly increasing.

Trends in Etiology-based Mortality From Chronic Liver Disease Before and During COVID-19 Pandemic in the United States.

BACKGROUND & AIMS: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic. METHODS: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC). RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD. CONCLUSION: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

Effect of Nonalcoholic Fatty Liver Disease (NAFLD) on COVID-19: A Single-Center Study of 3983 Patients With Review of Literature.

Background The presence of metabolic syndrome (MS) is associated with increased disease severity in patients with coronavirus disease 2019 (COVID-19). Non-alcoholic fatty liver disease (NAFLD) associated with or without MS may be related to increased morbidity and mortality in COVID-19, but large Indian studies are lacking. The present study was carried out to assess the impact of NAFLD on the clinical outcomes in patients with COVID-19 infection. Methods All patients with COVID-19 hospitalized at a tertiary care hospital in eastern India from April 4 to December 31, 2020, were included in the study. Patients who underwent non-contrast CT (NCCT) chest were evaluated for the presence of hepatic steatosis based on a validated criterion liver attenuation (HU) value lower than the spleen, absolute liver attenuation lower than 40 HU, and liver to spleen attenuation ratio less than 1. Patients were divided into two groups, those with or without fatty liver. Baseline characteristics including age, sex, liver function tests, and outcomes including duration of hospital stay and mortality were compared. Results A total of 6003 COVID-19-positive patients were admitted during the study period. Of these patients, 214 children (<18 years) with COVID-19 infection were excluded. One hundred and eight patients with a history of significant ethanol abuse were excluded from the analysis. NCCT scan was not done in 1698 patients. Finally, 3983 patients were included in the study. They were divided into two groups depending on the presence or absence of NAFLD. Of the 3983 patients, 814 (20.4%) had NAFLD. Overall in-hospital mortality among the study group was 6.4%. The mortality rate among patients with NAFLD was 6.7% while that in patients without fatty liver was 6% (P=0.381). Similarly, the mean duration of hospital stay was also comparable between both the groups (10.63±7.2days vs 10.65±6.6 days;P=0.66). Prevalence of NAFLD was similar in survivors and non-survivors; 759 of 2981 patients (25.4%) and 55 of 188 patients 29.2% (P=0.381), respectively. On univariate analysis, male sex, older age, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) along with low serum albumin and low absolute eosinophil counts (AEC) were associated with higher mortality. However, on multivariate analysis, only older age, male sex, and low albumin levels were associated with higher mortality. Surprisingly, a sub-group analysis showed that females without NAFLD were at a higher risk of mortality than those with fatty liver (4.9% vs 12.3%; P=0.006). Similarly, patients with lower AST levels had higher mortality compared to patients with significantly elevated AST levels (more than two times the upper limit of normal (ULN)), irrespective of the presence of fatty liver. Conclusions The prevalence of fatty liver in severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infected patients is similar to the general population in India, the presence of which is not a predictor of severe disease. However, mortality is higher in males and elderly patients.

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.

Mendelian Randomization Analysis Reveals No Causal Relationship Between Nonalcoholic Fatty Liver Disease and Severe COVID-19.

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has witnessed more than 4.5 million deaths as of the time of writing. Whether nonalcoholic fatty liver disease (NAFLD) increases the risk for severe COVID-19 remains unclear. We sought to address this question using 2-sample Mendelian randomization (TSMR) analysis approaches in large cohorts. METHODS: We performed large-scale TSMR analyses to examine whether there is a causal relationship between NAFLD, serum alanine aminotransferase, grade of steatosis, NAFLD Activity Score, or fibrosis stage and severe COVID-19. To maximize the power of this analysis, we performed a genome-wide meta-analysis to identify single nucleotide polymorphisms associated with NAFLD. We also examined the impact of 20 major comorbid factors of NAFLD on severe COVID-19. RESULTS: Univariate analysis of the UK Biobank data demonstrated a significant association between NAFLD and severe COVID-19 (odds ratio [OR], 3.06; P = 1.07 × 10-6). However, this association disappeared after demographic and comorbid factors were adjusted (OR, 1.57; P = .09). TSMR study indicated that NAFLD (OR, 0.97; P = .61), alanine aminotransferase level (OR, 1.03; P = .47), grade of steatosis (OR, 1.08; P = .41), NAFLD Activity Score (OR, 1.02; P = .39), and fibrosis stage (OR, 1.01; P = .87) were not associated with severe COVID-19. Among all NAFLD-related comorbid factors, body mass index (OR, 1.73; P = 7.65 × 10-9), waist circumference (OR, 1.76; P = 2.58 × 10-5), and hip circumference (OR, 1.33; P = 7.26 × 10-3) were the only ones demonstrated a causal impact on severe COVID-19. CONCLUSIONS: There is no evidence supporting that NAFLD is a causal risk factor for severe COVID-19. Previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity.

Vaccination in Chronic Liver Disease: An Update.

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

The Outcome in Cirrhosis after Hospital Discharge is Not Worsened with COVID-19 Infection: A Propensity Score-matched Analysis.

Background: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on the outcome of cirrhosis patients in the posthospitalization period is limited. Aims: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results: Cirrhosis patients with (n = 92) or without (n = 92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P = 0.520), over a similar duration of follow-up [186 (86-271) vs. 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed rehospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs. 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs. 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P = 0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.

Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence.

The coronavirus disease 2019 (COVID-19) pandemic has swept through nations, crippled economies and caused millions of deaths worldwide. Many people diagnosed with COVID-19 infections are often found to develop liver injury, which, in a small portion of patients, progresses to severe liver disease. Liver injury in the form of elevated transaminases, hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease. Those who already have insult to the liver from chronic disease, such as nonalcoholic fatty liver disease (NAFLD) may be at the greatest disadvantage. The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities. About 25% of the global population has NAFLD. With such a widespread prevalence of NAFLD, understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance. In this review, we present an overview of COVID-19 infection in patients with NAFLD.

Recent challenges facing patients with preexisting chronic liver disease in the era of the COVID-19 pandemic.

COVID-19 pandemic has resulted in a growing number of beds in common hospital wards and intensive care units being occupied by COVID-19 patients and the majority of medical and nursing staff being dedicated to their care. The present review summarizes the impact of COVID-19 on patients with underlying chronic liver diseases (CLD). Deferrals of all non-urgent activities in healthcare facilities, including a decrease in liver-clinic visits for patients with CLD, inadequate hepatocellular carcinoma (HCC) surveillance, and postponement of liver transplant activities are the most important consequences. Delays in viral hepatitis elimination programs were also reported, leading to future development of advanced CLD and HCC. Patients with chronic hepatitis B (CHB) and C without cirrhosis are not at risk for a more severe COVID-19 infection course. However, CHB status must be known in patients who are going to receive immunosuppression for preventing disease flare. In addition, checking for drug-drug interactions and potential hepatotoxicity reactions from agents administered to treat both SARS-CoV-2 and CLD are required. Patients with nonalcoholic fatty liver disease appeared to be at a high risk for severe COVID-19, even after adjustment for comorbidities. Patients with cirrhosis may develop decompensation, acute-on-chronic liver failure, or severe COVID-19. The mortality rate is worse in patients with high model for end-stage liver disease score, regardless of the etiology of cirrhosis.