We present the data obtained from 13 Asian countries and 62 investigators on the spectrum of liver injury and outcomes in CLD patients infected with SARS-Cov–2. Present study included 408 confirmed COVID–19 cases, of which 175 had no evidence of chronic liver disease and another 5 had inadequate data. (Fig–1). Altogether, 228 CLD patients were therefore included; 43(18.9%) with cirrhosis (including 18 decompensated cirrhosis) and 185 (81.1%) without cirrhosis.
Profile of patients of CLD with or without cirrhosis exposed to SARS-CoV–2 infection
The patients were mostly in the fifth or sixth decade with high rates of comorbidities. CLD without cirrhosis had male preponderance (57.8% versus 41.9%, p = 0.01) with MAFLD being more common (61.1% versus 32.5%, p = 0.003). The symptoms, laboratory parameters including leukocyte and platelet count and the severity of COVID–19 disease (18.6% versus 11.8%, p = 0.14) were comparable [Table–1].
More patients of cirrhosis had acute liver injury at admission (32.6% vs 20%, p<0.001) and also developed new onset liver injury in-hospital (39.5% versus 7%, p<0.001) those who had no ALI at presentation. The ALI occured in 40% of those without cirrhosis, but without decompensation. The ALI caused decompensation in 20.7% of cirrhotics, 9.1% developed AD and 11.6% ACLF.
COVID–19 related complications, i.e. acute kidney injury (18.6% versus 5.4%, p<0.001), respiratory failure (23.2% versus 8.6%, p<0.001) and hypotension (14% versus 3.8%, p<0.001) were more common in cirrhotics than CLD without cirrhosis. Those with cirrhosis needed more ICU care (25.6% versus 12.4%, p<0.001), developed higher liver related complications (32.6% versus 14.1, p = 0.007) leading to higher mortality (16.3% versus 2.7%, p = 0.002).
Profile of Cirrhosis with or without decompensation exposed to SARS-CoV–2 infection
The present study had 43 cirrhosis patients; 18 (41.8%) with prior decompensation, 16 (37.2%) with Child B and 3 (9%) with Child C. Most common etiology was viral (26, 60.5%), followed by MAFLD (14, 32.6%), alcohol (2, 4.7%) and autoimmune hepatitis (1, 2.3%) [Table S1].
Severe COVID–19 disease was more common among decompensated [33.3% versus 8%, OR = 5.5 (1.1–44.3), p = 0.02] with higher complications, i.e. acute kidney injury (33.3% versus 8%, p = 0.02), respiratory failure (50% versus 4%, p<0.001) and circulatory failure (27.8% versus 4%, p = 0.02). Decompensated cirrhotics had more liver injury [71.4% versus 13.8%, OR = 6.2 (1.55–29.13), p<0.001] at presentation. The liver related [44.4% versus 24%, OR = 3.24 (0.88–12.5), p = 0.08] and overall complications were more in decompensated cirrhosis with greater need for ICU care and higher mortality [OR = 11.3(1.5–288.1), p = 0.008].
SARS-CoV–2 infection related liver injury and outcome in CLD without cirrhosis
The liver injury in CLD patients without cirrhosis was noted more in those with severe COVID–19 disease [18% versus 5.7%, OR = 3.76(1.38–11.8), p = 0.004]. Patients of CLD with diabetes had higher risk [57.7% versus 39.7%, p = 0.01, OR = 2.061.14–3.73)] of liver injury. Patients with liver injury, needed more ICU admissions (20.6% versus 3.4%, p<0.001) with higher liver related (24.7% versus 2.3%, p<0.001) and overall complications [39.2% versus 6.8%, p<0.001). However, the recovery, hospital stay and associated mortality were comparable among those with or without liver injury [Table–2].
SARS-CoV–2 infection related liver injury and outcome in cirrhosis
The acute liver injury was seen in 14 (32.6%) patients [table–3]. The age, gender or presence of diabetes were comparable, but the risk of liver injury was more with diabetes (64.3% versus 17.2%, p = 0.002). Those with liver injury had higher CTP, MELD score and were often decompensated (55.6% versus 8%, p<0.001) and had also contracted more severe COVID–19 disease [42.8% versus 6.9%, OR = 9.5 (1.7–79.5)]. The COVID–19 related complications, such as renal, respiratory or circulatory failure were higher among cirrhotics with liver injury and required more ICU care (42.8% versus 3.4%, p = 0.001) with higher mortality (42.8% versus 6.9%, p–0.03). The liver related complications, i.e. worsening of jaundice, ascites, hepatic encephalopathy, variceal bleed and SBP happened more with COVD–19 related liver injury irrespective of decompensation.
Degree of liver injury over time and predictors of mortality:
The liver injury may be evident at presentation or develop and progress during the course of infection. The AST/ALT ratio, total bilirubin and R value (ALT/ALP ratio) were helpful in predicting survival in cirrhotics (Fig S1). The non-survivors had higher AST, and an AST/ALT ratio of >1.4 [AUROC–0.95, HR = 1.4(95CI 2.5–5.4), P = 0.02] predicted mortality among cirrhotics. The mean total bilirubin remained elevated to >9 mg/dl till death in non-survivors. They also had a low R-value [p = 0.02]. The liver injury occurred more towards the end of second week or early third week in non-cirrhotics (Fig-S2), but was evident at presentation or developed in the first week in cirrhotic patients.
The mortality was comparable among non-cirrhotics and compensated cirrhosis, despite more complications, liver injury and liver related complications in the later. This underscores the concept of adequacy of available hepatic reserve for recovery. It was further substantiated by the fact that decomepnsated cirrhosis had nearly twice the mortality seen in compensated cirrhosis [33% vs. 16.3%, OR = 2.5(95CI 0.7–9.4) p = 0.05]. The CTP score at presentation can predict survival in a cirrhosis [AUROC 0.94, sensitivity 86% and specificity of 94%] and a score above 8 showed high mortality (85.7%, HR = 19.2(95CI 2.3–163.3), p<0.001) [Fig–2].