Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

Table 1 Gastrointestinal adverse events in key studies investigating treatments for coronavirus disease 2019

Ref.	Dosage	n	Age, yr	Gender, male (%)	Incidence of adverse events in treatment vs control arm, n (%)
					Diarrhea	Vomiting	Abdominal pain	Constipation	Increased AST	Increased ALT	Drug termination due to AE
Lopinavir/ritonavir
Cao et al[31]	400/100 mg twice a day for 14 d	Tx 99; control 100	Median 58 (IQR 49-68)	120 (60.3)	4 (4.2) vs 0	6 (6.3) vs 0	4 (4.2) vs 2 (2.1)	NA	2 (2.1) vs 5 (5.1)	1 (1.1) vs 4 (4.0)	14%
Li et al[32]	200/50 mg, twice a day for 7-14 d	Tx 34; control 17	mean ± SD, 49.4 ± 14.7	40 (46.5)	9/34 (26.5) vs 0	NA	NA	NA	NA	1/21 (4.8) vs 0	1/34 (2.94)
Remdesivir
Beigel et al[50]	200 mg daily on day 1, followed by 100 mg daily on day 2-10	Tx 538; control 521	mean ± SD, 58.9 ± 15.0	684 (64.3)	NA	NA	NA	NA	15 (2.8) vs 20 (3.8)	8 (1.5) vs 9 (1.7)	49 (9.1)
Wang et al[51]	200 mg daily on day 1, followed by 100 mg daily on day 2-10	Tx 158; control 79	Median (IQR) 65 (56-71)	89 (56)	5 (3) vs 2 (3)	4 (3) vs 2 (3%)	NA	21 (14) vs 12 (15)	7 (5) vs 9 (12)	NA	18 (12)
Spinner et al[53]	200 mg daily on day 1, followed by 100 mg daily on day 2-5 or day 2-10	193; 193; 200	Median (IQR) 56 (45-66)	118 (61), 114 (60)	5% vs 6% vs 7%	NA	NA	NA	32 vs 32 vs 33	32 vs 34 vs 39	31 (7.8)
Hydroxychloroquine
Cavalcanti et al[70]	400 mg daily	Tx 221; control 227	mean ± SD, 50.3 ± 14.6	388 (55.3)	NA	0 vs 1 (0.6)	NA	NA	17 (8.5) vs 6 (3.4)	NA	NA
Boulware et al[71]	800 mg once, followed by 600 mg	Tx 414; control 407	Median (IQR) 41 (33-51)	196 (47.3)	81 (23.2) vs 15 (4.3) for diarrhoea or abdominal pain or vomiting	81 (23.2) vs 15 (4.3) for diarrhoea or abdominal pain or vomiting	81 (23.2) vs 15 (4.3) for diarrhoea or abdominal pain or vomiting	NA	NA	NA	17 (4.1)
Favipiravir
Chen et al[80]	1600 mg twice a day on day 1, followed by 600 mg twice daily on day 2-10	Tx 116; control 120	NA	59 (50.86)	NA	NA	NA	NA	10 (8.62)	NA	Nil
Nitazoxanide
Rocco et al[82]	500 mg 3 times per day	Tx 194; control 198	18-77	101 (52)	57 (29.4) vs 49 (24.7)	9 (4.6) vs 3 (1.5)	10 (5.2) vs 5 (2.5)	NA	NA	NA	Nil
Tocilizumab
Stone et al[120]	Tocilizumab 8 mg/kg IV inf not to exceed 800 mg	Tx 161; control 82	Median (IQR) 61.6 (46.4-69.7)	96 (60)	NA	NA	NA	NA	6 (3.7) vs 3 (3.7) for grade 3 or 4	8 (5.0) vs 4 (4.9) for grade 3 or 4	NA

AE: Adverse event; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; inf: Infusion; IQR: Interquartile range; IV: Intravenous; NA: Not available; Tx: Treatment.