Table 1.

Time-course of the clinical picture during acute yellow fever and late-relapsing hepatitis after yellow fever.

Timeline Month/DPS		Laboratory Tests (Followed by Normal Range Values/unit) #
		AST	ALT	TBil	DBil	APhos	GGT	INR	Urea	Cr	CK
		10–40 U/L	10–40 U/L	0.3–1.0 mg/dL	0.1–0.3 mg/dL	30–120 U/L	9–50 U/L *		8–20 mg/dL	0.7–1.30 mg/dL *	55–170 U/L *
	4	4560	3710	na	na	na	na	na	118	2.17	na
	7 A	781	999	9.8	8.9	139	495	1	85.1	2	42
	8 B	537	674	9.5	8.4	144	855	0.88	47	1.3	na
Jan	9	434	571	9.1	8	154	9399	na	53.6	1.4	na
	10	375	508	8.3	7.2	145	1057	1	39.1	1.2	38
	11	297	456	6.7	5.8	159	1103	na	na	na	na
	12	235	401	5.2	4.4	173	1074	na	40.2	1.4	na
	14 C	253	371	5.1	4.2	149	869	1	39.7	1.2	na
Feb	36 D	233	353	1.5	0.9	147	530	1.02	33.5	1.5	na
	64	677	797	10.4	6.5	142	355	1	44	1.3	na
	70	655	819	13.9	7	485	401	1.06	51	1.2	na
Mar	78 E	744	862	7.2	6.2	210	431	1.03	43.5	1.4	na
	80 F	660	1007	6.5	5.5	164	624	1	na	na	na
	82 G	793	973	6.4	5.5	163	447	1.24	na	na	na
	83 H	903	1235	6.1	5.2	171	572	1	na	na	na
	85 I	987	1285	5.7	4.9	182	448	1	na	na	na
Apr	87	1002	1666	6.5	5.4	193	444	1	na	na	na
	89 J	883	1252	5.9	4.9	192	525	1	48	1.4	na
	92	769	904	3.8	3.3	207	554	1	51.4	1.4	na
	93	na	na	na	na	na	na	na	na	na	na
	95	743	863	3.6	3.1	229	547	na	45	1.3	na
May	124	78	108	1.3	1	139	199	1	34.9	1.2	na
Jul	186	21	28	0.84	0.2	na	71	na	44	1.05	na
	197 K	27	39	1	0.4	65	72	1	43.1	1.2	na
Nov	306 L	22	26	0.8	0.2	72	na	1.12	37.1	1.1	na

DPS: day after the first symptoms of yellow fever onset. na: not available. AST: aspartate aminotransferase, ALT: alanine aminotransferase, APhos: alkaline phosphatase, GGT: gamma-glutamyltransferase, TBil: total bilirubin, DBil: direct bilirubin, Cr: Creatinine, CK: Creatine kinase, INR: international normalized ratio (INR) for prothrombin time. The days when the patient was hospitalized are shown in blue, the periods when the patient had elevated AST and ALT are shown in green and periods when the patient had jaundice are in orange. A: anti-HIV-1 and anti-HIV-2 non-reactant. B: anti-YFV IgM and IgG reagent; anti-DENV IgM non-reactant. C: anti-YFV IgM reagent. Hospital discharge. D: anti-YFV IgG reagent. E: Serum and urine were tested by qPCR for YFV [5] and results were negative. Serum was tested by qPCR and negative for DENV [6,7], CHIKV [8], and pan-flaviviruses [9]. Anti-YFV IgM and IgG reagent. Neutralizing antibodies anti-YFV were detected by PRNT₈₀ (up to sera dilution 1:80) [10]. Patient was rehospitalized and computed tomography indicated mild hepatomegaly but no biliary obstruction. F: Non reactant tests for anti-smooth muscle, anti-mitochondrial, anti-nuclear factor HEP2, anti-neutrophil cytoplasm antibodies (P-ANCA and C-ANCA). Total IgG = 962 mg/dL (6417.6 µmol/L) (normal range¹¹: 800–1500 mg/dL), erythrocyte sedimentation rate = 41 mm/hour (normal range for male¹¹: 0–15 mm/hour), serum copper = 138 µg/dL (21.72 µmol/L) (normal range¹¹ = 100–200 μg/dL), tree T4 = 0.98 ng/dL (12.61 pmol/L) (normal range¹¹: 0.8–1.8 ng/dL), thyroid-stimulating hormone = 2.53 µU/mL (normal range¹¹: 0.5–4.0 μU/mL), ferritin 7.46 ng/mL (16.76 µg/L) (normal range for male¹¹: 24–336 ng/mL), and ceruloplasmin = 29.1 mg/dL (2.17 µmol/L) (normal range¹¹: 25–43 mg/dL). G: Non-reactant tests for: anti HIV-1 and HIV-2; anti-HCV; anti-HAV IgM and IgG; anti-Epstein Barr virus IgM and IgG; anti-toxoplasma IgM. Reagent tests for anti-toxoplasma IgG. H: Anti-YFV IgM and IgG reagent. Neutralizing antibodies anti-YFV were detected by PRNT₈₀ (up to sera dilution 1:80) [10]. I: Ultrasonography indicated non-specific increased periportal echogenicity and mild hepatomegaly. J: Tests were run and non-reactant for IgM anti-HBc, total anti-HBc, and HBsAg. Colangio magnetic resonance indicated mild splenomegaly. K: anti-YFV IgG reagent. L: anti-YFV IgM and IgG reagent. # normal range values are presented according to American Board of Internal Medicine Laboratory Test Reference Ranges—January 2020 [11]. * normal range values for males. Normal range are presented in International System Units (SI), calculated by the multiplication of values in conventional units per conversion factor (CF), as follows: AST: 10–40 UL × 0.0166 (CF) = 0.17–0.66 microkatal units/L, ALT: AST: 10–40 UL × 0.0166 (CF) = 0.17–0.66 microkatal units/L, TBil: 0.3–1.0 mg/dL × 17.1 (CF) = 5.13–17.1 µmol/L, DBil: 0.1–0.3 mg/dL × 17.1 (CF) = 1.71–5.13 µmol/L, AP: 30–120 U/L × 0.01667 (CF) = 0.5–2.0 microkatal units/L, GGT: 9–50 U/L × 0.016667 (CF) = 0.15–0.83 microkatal units/L, Urea: 8–20 mg/dL × 357.146 (CF) = 2857.14–7142.86 µmol/L, Creatinine: 0.7–1.30 × 88.42 (CF) = 61.89–114.95 µmol/L, CK: 55–170 U/L × 0.01667 (CF) = 0.92–2.83 microkatal units/L, total IgG:800–1500 mg/dL × 6.67 (CF) = 5336.9–10,006.7 µmol/L, ferritin: 24–336 ng/mL × 1.0 (CF) = 24–336 µgl/L, free T4 = 0.8–1.8 ng/dL × 12.86 (CF) = 10.29–23.16 pmol/L, ceruloplasmin = 25–43 mg/dL × 0.6667 (CF) = 1.86–3.20 µmol/L, serum copper: 100–200 μg/dL × 0.157 (CF) = 15.74–31.47 µmol/L).