Hepatitis B Virus-Related Cryoglobulinemic Vasculitis: Review of the Literature and Long-Term Follow-Up Analysis of 18 Patients Treated with Nucleos(t)ide Analogues from the Italian Study Group of Cryoglobulinemia (GISC)

Abstract

Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90–100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.

Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy

“…As for the HCV-related cryoglobulinemic glomerulonephritis, RTX remains the first-line immunosuppressive agent. Similar to this, the low-grade NHL patients who received NAs required subsequent chemotherapy or immunotherapy since they did not experience a hematological response [ 9 , 23 ].…”

“…Similar to the HCV-related MC, the prevalent renal manifestation is membranoproliferative glomerulonephritis. Low-grade indolent NHL is observed in 10% of the patients [ 9 ]. In rare cases, the disease is life-threatening, affecting the central nervous system, the gastrointestinal tract, and the heart [ 4 ].…”

“…Compared to the virologic response, the clinical and immunological responses are noticeably less remarkable. In a consistent number of cases, after receiving the NAs therapy, the vasculitis symptoms such as minor purpura, asthenia, and arthralgias may vanish or improve [ 7 , 9 ]. The NAs can eradicate the virus in patients with sensory motor peripheral neuropathy, but they frequently remain as clinical non-responders.…”

“…The NAs can eradicate the virus in patients with sensory motor peripheral neuropathy, but they frequently remain as clinical non-responders. Rituximab (RTX) can obtain a clinical and immunological improvement [ 9 ], but its use can be harmful.…”

“…In a few studies with HBV-related glomerulonephritis, some improvement of the renal function and urinary abnormalities have been reported following NAs therapy [ 6 , 9 , 20 ]. However, the majority of the patients eventually underwent RTX therapy or aphaeresis, and in a way that is similar to HCV-associated MC, they may achieve immunological and functional improvement [ 21 , 22 ].…”