Human hepatitis viruses-associated cutaneous and systemic vasculitis

Table 1 Common characteristics and comparative features in five members of human hepatitis viruses

	HAV	HBV	HCV	HDV1	HEV
Family; Genus	Picornaviridae Hepatovirus	Hepadnavirida Orthohepadnavirus	Flaviviridae Hepacivirus	Deltaviridae Deltavirus	Hepeviridae Orthohepevirus
Discovery2; Frequency	1983 Highest in AH	1979 Highest in CH	1989 Second in CH	1986 Less in CH	1990 Less in AH
Genome3; Length; Diameter4; Envelope5; Receptor	Linear ssRNA; 7500 nt; 27-32 nm; Quasi-envelope; Unknown	Circular dsDNA; 3200 nt; 42 nm; Envelope; NTCP, HSP	Linear ssRNA; 9600 nt; 55-65 nm; Envelope; CD81, SR-BI	Circular ssRNA; 1700 nt; 36-43 nm; Envelope; NTCP, HSP	Linear ssRNA; 7200 nt; 30-34 nm; Quasi-envelope; Unknown
Incubation; Age6; Course	14-30 d; Children; Acute	30-180 d; Any; Acute/chronic	14-180 d; Any; Acute/chronic	14-160 d; Any; Acute/chronic7	14-70 d; Adults; Acute
Route of spread	Enteric, sexual	Parental, sexual, vertical	Parental, sexual	Parental, sexual, vertical	Enteric, vertical, parenteral
Hepatitis diagnosis	Anti-HAV IgM	Anti-HBc IgM, HBs antigen, DNA by PCR	Anti-HCV IgG, RNA by PCR	Anti-HDV IgM, RNA by PCR	Anti-HEV IgM, RNA by PCR
Vaccine; Post-exp; Av agent	Available; Ig/vaccine; Not available	Available; Ig/vaccine; NA, IFN-α	Not available; Not effective; DAA agent	HBV vaccine; Not available; IFN-α	Available in China; Not available; Not available
FH8; LC/HCC; Prognosis9	Very rare; Nil; Full recovery	Very rare; Yes; Chronic carrier	Extremely rare; Yes; High carrier rate	Yes; Yes; Chronic carrier	Yes; Nil; Full recovery

¹Co-infection/superinfection with hepatitis B virus.

²By cloning and sequencing.

³Partial dsRNA in hepatitis B virus.

⁴Diameter of virion.

⁵Quasi-envelop with internal protein rather than viral glycoprotein.

⁶Commonly affected age.

⁷Progress to chronicity in 80% superinfection/5% co-infection hepatitis B virus.

⁸Up to 20% in superinfection with hepatitis B virus and pregnant women.

⁹Poorer in hepatitis B virus superinfection with hepatitis delta virus and pregnant woman with hepatitis E virus. AH: Acute hepatitis; Av: Antiviral; CH: Chronic hepatitis; DAA: Direct-acting antiviral; DNA: Deoxyribonucleic acid; ds: Double-stranded; Post-exp: Post-exposure; FH: Fulminant hepatitis; HBc: Hepatitis B virus core antigen; HBs: Hepatitis B virus surface antigen; HCC: Hepatocellular carcinoma; HSP: Heparan sulfate proteoglycans; IFN: Interferon; Ig: Immunoglobulins; LC: Liver cirrhosis; NA: Nucleoside/nucleotide analogues; nt: Nucleotide; NTCP: Sodium taurocholate co-transporting polypeptide, PCR: Polymerase chain reaction; RNA: Ribonucleic acid; SR-BI: Scavenger receptor class B type I; ss: Single-stranded.

Table 2 Clinical and medication profiles in five polyarteritis nodosa patients naïve to human hepatitis virus infection¹

No	Age/sex	Initial symptom	Diagnosisperiod2	BVAS/FFS3	HHV status4	Follow-up manifestation	Therapy	Outcome
1	23/F	Arthralgia, rash5	2 mo	6/0	Negative	Joint, PN, skin	Az, Cs	Survival, remission
2	29/F	Arthralgia, fever, rash5	1 yr	11/0	Negative	FN, GI, joint, PN, skin	Az, Cs	Survival, remission
3	38/F	Fever, rash5	1 yr 5 mo	14/0	Negative	Joint, PN, skin	Az, Cs, Cy	Survival, remission
4	39/M	Rash	3 yr 10 mo	18/1	Negative	Kidney, skin	Az, Cs, RTX	Survival, chronic renal insufficiency
5	42/M	Arthralgia, rash	6 mo	7/0	Negative	Joint, PN, skin, kidney, testis	ADA, Az, Cs, Cy	Survival, remission

¹Enrollment from 2012 to 2019.

²Time period from initial symptoms to the established diagnosis.

³Calculation at the disease diagnosis.

⁴Human hepatitis virus status, including examinations for hepatitis A virus, hepatitis B virus, hepatitis C virus, and hepatitis delta virus.

⁵Erythematous nodosum-like skin lesions. ADA: Adalimumab; Az: Azathioprine; BVAS: Birmingham vasculitis activity score; Cs: Corticosteroids, Cy: Cyclophosphamide; F: Female; FFS: Four-factor score, including age above 65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency; FN: Foot necrosis; GI: Gastrointestinal; HHV: Human hepatitis virus; M: Male; PAN: Polyarteritis nodosa; PN: Peripheral neuropathy; RTX: Rituximab.

Table 3 Comparisons of clinical and outcome profiles in polyarteritis nodosa from various case series with different hepatitis B virus-infected frequencies

Source of cases	No/age1 F%	HBV status	Fever	AM	Skin	PN	GI	Renal	TestisM%	Therapy	Death
Taiwan	12/31, 67%	0%	67%	58%	75%	42%	50%	75%	50%	Az, Cs, Cy, Bio	33%
United Kingdom	17/49, 24%	31%	76%	77%	65%	59%	65%	77%	NA	Cs, Is	38%
United States	53/54, 34%	11%	31%	55%	58%	60%	25%	66%	NA	Cs, Cy	42%
Canada	45/54, 47%	19%	63%	51%	44%	51%	53%	44%	4%	Cs, Cy	53%
South Korea	27/47, 37%	56%	52%	30%	44%	63%	48%	48%	24%	Az, Cs, Cy, Is	15%
France	348/51,37%	35%	64%	59%	50%	74%	38%	51%	17%	Av, Cs, Cy, Is	25%
India	27/38, 26%	26%	52%	37%	37%	82%	30%	59%	30%	Av, Az, Cs, Cy	11%

¹Mean age at disease diagnosis. AM: Articulomuscular; Az: Azathioprine; Av: Antiviral agent; Bio: Biologics; Cs: Corticosteroids; Cy: Cyclophosphamide; F: Female; GI: Gastrointestinal; Is: Immunosuppressive agent, M: Male; NA: Not available; PN: Peripheral neuropathy.