Table 2.

Extrahepatic Manifestations of HBV

Types of manifestations	Symptoms
Periarteritis or polyarthritis nodosa (PAN)	•Can present in all stages of HBV infection but more commonly within the first 6 mo of acute HBV infection67, 68, 69 •Associated with IC (HBsAg and/or HBeAg) deposition into blood vessels70,71 •HBV-associated PAN have more frequent relapses of vasculitis and mortality compared to primary PAN,67, 68, 69 until HBV is fully suppressed •ANCAs and complement levels are normal70,71 •CTA or MRA diagnose HBV-associated PAN when there are multiple aneurysms in the affected organ72
Mixed cryoglobulinemia (MC) vasculitis	•90% of cases are due to HCV infection, and 10% of cases are due to lymphoproliferative disorders, rheumatic disorders, HBV, or HIV infections73, 74, 75 •Like HCV, HBV-mediated MC is due to IC (HBsAg and anti-HBs) depositing into the small-medium blood vessels76 •CD20-positive B cells are expanded and activated77
Rheumatological manifestations	•Symmetric and nondestructive arthralgia or arthritis involves the hands, feet, and sometimes large joints67,78 •IC containing HBsAg and activated complement deposit into synovium67 •Anti-cyclic citrullinated peptide antibody (5%), antinuclear antibody (10%), rheumatoid factor (25%) can be positive67
Skin manifestations	• Occur in >50% of acute HBV infections78 ○ Present as maculopapular, pruritic, or petechial lesions78 •In chronic HBV, sequela of cutaneous vasculitis are from immunoglobulins, complements, and HBsAg depositing into the vessel walls78 •These deposits can be found on skin biopsies78
Renal manifestations	•3%–5% of chronic HBV infections develop renal involvement17,79 •Associated with IC deposition in the glomeruli80 •MN and MPGN are the most common77 •HBV genotype A is associated with higher incidences of MN and MPGN77 •HBV-associated MN: ± anti-PLAR, predominantly associated with IgG1 subtype81 •Idiopathic MN: + anti-PLAR, predominantly associated with IgG481
Hematologic malignancies	•Associated with NHL and DLCL •In a nationwide study in Taiwan of those with HBV infection, the hazard ratio was 2.2 for NHL, 2.7 for DLCL, and 3.1 for the other B-cell lymphoma18 •Patients with DLCL and chronic HBV had a poorer 2- and 5-y survival rate and progression-free survival rate82

ANCAs, antineutrophil cytoplasmic antibodies; anti-PLAR, antiphospholipase A2 receptor antibodies; CTA, computed tomography angiography; DLCL, diffuse large B-cell lymphoma; Ig, immunoglobulin; MN, membranous nephropathy; MPGN, membranoproliferative glomerulonephropathy; MRA, magnetic resonance angiography; NHL, non-Hodgkin lymphoma.