Transient immune hepatitis as post-coronavirus disease complication: A case report

Table 1 Laboratory assessment at hospital admission and throughout follow-up

Parameter	Day 3	Day 7	Day 11	Day 17	Day 20	Day 24	Day 25	Day 26	Day 27	Day 32	Day 43	Day 69	Day 104	Day 145	Day 193	Day 257
Hematology
White blood cells (3.6-9.6) × 103/µL	4.5	3.9	5.8	7.6		6.6		6.7				5.7	5.7			4.3
Neutrophils (1.4-6.5) × 103/µL	1.8	1.7	3.0	3.8		3.4		3.5				3.1	3.3			2.0
Lymphocytes (1.2-3.4) × 103/µL	1.8	1.7	2.0	2.7		2.2		2.2				1.7	1.6			1.7
Hemoglobin (12.1-17.2) g/dL	15.6	15.2	15.5	15.8		15.8		15.2				15.0	15.6			14.3
Platelets (200-400) × 103/µL	205	188	266	311		265		254				245	255			215
Coagulation
D-dimers hs (50-230) ng/mL	68	38	10		18	56		30		23	61
Activated partial thromboplastin time (24-38) s	31.6			33.4	35.4						31.9	32.3				27.2
Prothrombin concentration (80-115) %	75	95	73.9	89	84	90		89	83	86	83	75	72.6			86.9
Biochemistry
ALT (4-50) U/L	28	64	211	309	349	736	627	592	523	270	46	23	19			13
AST (17-59) U/L	28	50	59	13	94	290	196	148	113	63	28	24	22			18
Total bilirubin (0.2-1.3) mg/dL	0.4	0.4	0.4	0.6	0.5	0.6	0.5	0.5	0.8	0.6	0.6	0.6	0.6
Direct bilirubin (0.0–0.4) mg/dL	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.2	0.2	0.2	0.2	0.2
GGT (15-85) U/L	29	38		64	81	94	93	92	86	74	46	26	22			14
Alkaline phosphatase (38-126) U/L	58			69		71	65	67	65		69
Albumin (3.5-5) g/dL	4.7				4.5	4.9			4.6	4.8
Amylase (30-110) U/L			59			57
Lipase (23-300) U/L			35			37
Creatine kinase (55-170) U/L	89	59	46	52	56	62	59	58	54	78						117
Creatine kinase-MB (1-16) U/L	9	6	6	7	4	7	6	10	7	5						9
Fasting plasma glucose (74-106) mg/dL	84	102	97	86	88	98	90		92	84	89	87	96			97
Lactate dehydrogenase (120-246) U/L	189	221	214	252	258	426	378	285	245	260	189	172	162			145
Total proteins (6.3-8.2) g/dL	7.9	8.0	8.2	8.2	7.9	8.7				8.2	8.5	7.8	7.9			7.8
Cholesterol (50-200) mg/dL	150					196										151
HDL-cholesterol (40-60) mg/dL						46										48
Total lipids (400-800) mg/dL						705										482
Triglycerides (15-150) mg/dL	62					174										52
Creatinine (0.7-1.3) mg/dL	0.9	0.8	0.8	0.7	0.8	0.8	0.6	0.6	0.9	0.7	0.7	0.7	0.7			0.6
Urea (15-45) mg/dL	31	27	27	27.5	20	28		28	29	34	34	41	33			35
Sodium (137-145) mmol/L	143	141	142	142	141	139	140		141	141	142	141				143
Potassium (3.6-5.0) mmol/L	4.3	4.4	4.6	4.4	4.4	4.7	4.7		4.8	4.6	4.5	4.3				4.7
Calcium (8.4-10.2) mg/dL	9.3		9.4	9.9	9.7					9.7	10.0	9.9	9.9			9.9
Inflammatory markers
C-reactive protein (0-3) mg/L	6.20	1.62		0.99								1.75	1.37			0.78
Erythrocyte sedimentation rate mm/h			10								16	8
Fibrinogen (200-393) mg/dL	250	243	196	227	221	254		246	244	269	260	221
Ferritin (22-322) ng/mL	149.7		173.8					166.3
IL-6 (0-9.7) pg/mL	0.453		0.420
TNF-α (0-1.9) pg/mL	0.0		0.0
Procalcitonin (0-0.5) ng/mL	0.05		0.05
Cardiac markers
Myoglobin (0-99.3) ng/mL	47.4					36.7
NT-proBNP (0-125) ng/L	5					5
Troponin I (0-0.16) ng/mL	0.03					0.03
SARS-CoV-2 antibodies
Total SARS-CoV-2 Ab (0.00-0.99) S/CO		29.2	62	110	132	166	173	180	188	225	305	498	721	865	654	85.1

Days are counted since symptom onset. Day 3 was the first day of hospital admission (baseline laboratory assessment).

Bold font indicates laboratory values outside of the normal range. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; IL-6: Interleukin 6; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; NT-proBNP: N-terminal pro-B-type natriuretic peptide; TNF-α: Tumor necrosis factor-alpha; HDL: High-density lipoprotein.

Table 2 Differential diagnosis of hepatic cytolysis

Hypothesis	Investigation and result
Drug-induced liver injury	No drugs recently administered
Systemic replication of SARS-CoV-2	Negative SARS-CoV-2 RT-PCR from blood and nasopharyngeal + oropharyngeal swabs
COVID-19 cytokine storm	Timing–day 24
	Normal inflammatory markers
	Normal chest CT at baseline and on day 24
Infections with other hepatotropic viruses	Negative: HAV IgM, HBsAg, HCV Abs, HEV IgM and HEV-RNA, adenovirus IgM, coxsackie virus IgM, echo virus IgM, HSV1+2 IgM, EBV IgM, CMV IgM.
Post-COVID-19 immune hepatitis	Rapidly increasing SARS-CoV-2 antibodies (chemiluminescence)

COVID-19: Coronavirus disease-19; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; RT-PCR: Real-time reverse transcription polymerase chain reaction; IL-6: Interleukin 6; CT: Computed tomography; HAV: Hepatitis A virus; HCV Abs: Hepatitis C virus antibodies; HEV: Hepatitis E virus; HSV: Herpes simplex virus; HBsAg: Hepatitis B surface antigen; IgM: Immunoglobulin M; EBV: Epstein-Barr virus; CMV: Cytomegalovirus.