Probable case of drug reaction with eosinophilia and systemic symptom syndrome due to combination therapy with daclatasvir and asunaprevir

Table 1 Laboratory findings before antiviral therapy and at the onset of adverse events

On day 14 of antiviral therapy				Virological analysis before antiviral therapy
Hematology		Virus markers		Virus marker
WBC (μL)	12130	IgM-HAV Ab	(-)	HCV RNA (Log IU/mL)	5.9
Neutrophils (%)	82	HBs Ag	(-)
Lymphocytes (%)	10	IgM-HBc Ab	(-)	Drug resistant variants
Monocytes (%)	6	HBV DNA	(-)	NS3/V36A	(-)
Eosinophils (%)	1	IgA-HEV Ab	(-)	NS3/T54A	(-)
RBC (μL)	4000000	IgM-HSV Ab	(-)	NS3/T54S	(-)
Hb (g/dL)	13.2	IgG-HSV Ab	(+)	NS3/Q80L	(-)
Plt (μL)	79000	IgM-HHV6 Ab	(-)	NS3/Q80R	(-)
		IgG-HHV6 Ab	(+)	NS3/R155K	(-)
Blood chemistry		IgM-CMV Ab	(-)	NS3/R155Q	(-)
TP (g/dL)	7.4	IgG-CMV Ab	(+)	NS3/R155T	(-)
Albumin (g/dL)	3.3	IgM-EBV VCA Ab	(-)	NS3/A156S	(-)
T-Bil (mg/dL)	1.9	IgG-EBV VCA Ab	(+)	NS3/A156T	(-)
D-Bil (mg/dL)	0.7	EBNA Ab	(+)	NS3/A156V	(-)
AST (IU/L)	15			NS3/D168A	(-)
ALT (IU/L)	22	Endocrine		NS3/D168E	(±)2
ALP (IU/L)	284	TSH (μIU/mL)	1.7	NS3/D168H	(-)
γ-GTP (IU/L)	33	fT3 (pg/mL)	2.81	NS3/D168T	(-)
LDH (IU/L)	147	fT4 (ng/dL)	1.1	NS3/D168V	(-)
ChE (IU/L)	257			NS3/V170I	(+)2
T. Chol (mg/dL)	126	Serology		NS5A/L31F	(-)
BUN (mg/dL)	28	IgA (mg/dL)	130	NS5A/L31M	(-)
Cr (mg/dL)	1.4	IgE (mg/dL)	526	NS5A/L31V	(-)
UA (mg/dL)	5.4	IgG (mg/dL)	2225	NS5A/Y93H	(±)2
CPK (IU/L)	60	IgM (mg/dL)	104
CRP (mg/dL)	3.5	RF	(-)
BNP (pg/mL)	20.1	ANA	× 40 (+)
Fe (μg/dL)	123	AMA	(-)
Ferritin (ng/mL)	115	ASMA	(-)
Hyaluronic acid1 (ng/mL)	179
Collagen-41 (ng/mL)	298	Tumor markers
		PIVKA-2 (mAU/mL)	19
Blood coagulation		AFP (ng/mL)	6.6
PT (%)	66.4
PT-INR	1.22	DLST
		Daclatasvir	(-)
		Asunaprevir	(-)

¹Hyaluronic acid and collagen-4 were measured before antiviral therapy. Drug resistant variants in the NS3 and NS5A regions were measured by invader method;

²D168E and Y93H mutations were not detected by direct sequencing. Only V170I was detected by direct sequencing. γ-GTP: γ-glutamyl transpeptidase; Ab: Antibody; AFP: α-fetoprotein; Ag: Antigen; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AMA: Antimitochondrial antibody; ANA: Antinuclear antibody; ASMA: Antismooth muscle antibody; AST: Aspartate aminotransferase; BNP: Brain natriuretic polypeptide; BUN: Blood urea nitrogen; ChE: Cholinesterase; CMV: Cytomegalovirus; CPK: Creatine phospho kinase; CRP: C-reactive protein; D-Bil: Direct bilirubin; DLST: Drug-induced lymphocyte stimulation test; EBNA: Epstein–Barr virus nuclear antigen; EBV: Epstein-Barr virus; fT3: Free triiodothyronine; fT4: Free thyroxine; HAV: Hepatitis A virus; Hb: Hemoglobin; HBc: Hepatitis B virus core; HBs: Hepatitis B virus surface; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HEV: Hepatitis E virus; HHV: Human herpes virus; HSV: Herpes simplex virus; Ig: Immunoglobulin; INR: International normalized ratio; LDH: Lactic dehydrogenase; PIVKA: Protein induced by vitamin K absence or antagonist; Plt: Platelets; PT: Prothrombin time; RBC: Red blood cell; RF: Rheumatoid factor; T-Bil: Total bilirubin; T.Chol: Total cholesterol; TP: Total protein; TSH: Thyroid stimulating hormone; UA: Uric acid; WBC: White blood cell.