What is the relationship between Cryoglobulinemia and Hepatitis C (Hep C)?

From the Guidelines

Cryoglobulinemia is strongly associated with Hepatitis C (HCV) infection, with the vast majority of mixed cryoglobulinemia cases attributed to HCV 1.

Relationship Between Cryoglobulinemia and Hepatitis C

• The presence of HCV infection is a major risk factor for the development of mixed cryoglobulinemia syndrome (MCS), which is characterized by the triad of purpura, fatigue, and arthralgia 1.
• Circulating cryoglobulins are frequently detected in HCV-positive patients, although only a minority of patients with chronic HCV infections develop frank MCS, typically women aged more than 50 years 1.
• The treatment of HCV-related MCS should be tailored to each individual patient based on the progression and severity of the clinical manifestations 1.

Treatment Approach

• The recommended treatment approach typically involves a combination of antiviral therapy to treat the underlying HCV infection, and immunosuppressive therapy to manage the symptoms of cryoglobulinemia 1.
• For antiviral therapy, the preferred treatment is a direct-acting antiviral (DAA) regimen, such as sofosbuvir and ledipasvir for 12 weeks, or other DAA combinations like glecaprevir and pibrentasvir for 8-12 weeks 1.
• In addition to antiviral therapy, immunosuppressive treatment with rituximab may be considered to reduce the production of cryoglobulins and alleviate symptoms, particularly in patients with severe MCS 1.
• In severe cases, plasmapheresis may be necessary to remove cryoglobulins from the blood, although this should be restricted to life-threatening situations in which other therapeutic approaches have failed or could not be used 1.

Monitoring and Adjustment of Therapy

• It is essential to monitor the patient's response to treatment and adjust the therapy as needed to manage symptoms and prevent organ damage 1.
• The treatment approach should aim to prevent irreversible organ damage, reduce pain, and improve the patient's quality of life 1.

From the Research

Relationship between Cryoglobulinemia and Hepatitis C

The relationship between cryoglobulinemia and hepatitis C (Hep C) is well-established, with Hep C infection being a major cause of cryoglobulinemia [ 2, 3,4,5,6 ].

Prevalence of Cryoglobulinemia in Hep C Patients

• Cryoglobulins are detected in 45.7% of patients with chronic Hep C infection 3
• Mixed cryoglobulinemia is observed in 30% to 40% of patients with Hep C 2
• Symptoms or signs associated with cryoglobulinemia develop in 12.3% to 27% of patients with Hep C 3, 2

Clinical Manifestations of Cryoglobulinemia in Hep C Patients

• Cutaneous manifestations, such as recurrent purpura 2, 6
• Articular manifestations, such as joint pains 2
• Neurologic manifestations, such as peripheral neuropathy 2, 6
• Renal manifestations, such as membranoproliferative glomerulonephritis 2, 6
• Gastrointestinal vasculitis 6
• Pulmonary hemorrhage 6
• Central nervous system (CNS) involvement 6
• Myocardial involvement 6

Treatment and Outcome of Cryoglobulinemia in Hep C Patients

• Direct-acting antiviral (DAA) therapies have improved the treatment of Hep C-associated cryoglobulinemia, with sustained virological response (SVR) rates greater than 95% 2, 4
• DAA therapies have also improved extrahepatic manifestations, such as cryoglobulinemic vasculitis 2, 4
• Interferon-based therapies have been associated with lower rates of viral cure in patients with cryoglobulinemia 4
• Patients with severe vasculitis may still require concomitant immunosuppression 4
• Mortality rates for life-threatening cryoglobulinemic manifestations range from 20% to 80% 6