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Early HCV therapy reduces risk for non-Hodgkin lymphoma, stroke

Although sustained virologic response after antiviral therapy for hepatitis C reduces the risks for several extrahepatic manifestations, researchers found that early initiation of treatment may be required to reduce the risk for glomerulonephritis, non-Hodgkin lymphoma and stroke.

“[Antiviral therapy] for HCV infection is beneficial for patients with HCV-associated mixed cryoglobulinemia or indolent [non-Hodgkin lymphomas (NHLs)], as they can have complete resolution of symptoms of cryoglobulinemia and lymphoma regression,” Parag Mahale, PhD, MPH, from the National Cancer Institute, Maryland, and colleagues wrote. “However, this risk reduction was not observed when [antiviral therapy] was started 2 or more years after the HCV index date.”

Mahale and colleagues retrospectively reviewed the data of 160,875 adults with HCV from the Veterans Affairs HCV Clinical Case Registry, most of whom were men (97.1%), aged between 50 years and 59 years (52.1%), and had genotype 1 (54.7%). Approximately 19% of the patients received antiviral therapy, 34% of whom achieved SVR.

Most extrahepatic manifestations had an incidence rate less than 1 per 1,000 person-years, including mixed cryoglobulinemia, porphyria cutanea tarda (PCT), lichen planus, NHL and coronary heart disease; whereas glomerulonephritis, diabetes and stroke occurred more frequently in all three patient groups: untreated, treated without SVR and treated with SVR. Glomerulonephritis, diabetes and stroke occurred less frequently in patients who achieved SVR compared with treated patients without SVR.

Multivariate analysis showed that patients who achieved SVR had significantly lower risks for mixed cryoglobulinemia (HR = 0.61; 95% CI, 0.39-0.94), glomerulonephritis (HR = 0.62; 95% CI, 0.48-0.79), PCT (HR = 0.41; 95% CI, 0.2-0.83), NHL (HR = 0.64; 95% CI, 0.43-0.95), diabetes (HR = 0.82; 95% CI, 0.76-0.88) and stroke (HR = 0.84; 95% CI, 0.74-0.94) compared with untreated patients.

Among those who did not achieve SVR, the risks for glomerulonephritis (HR = 0.82; 95% CI, 0.69-0.96) and stroke (HR = 0.82; 95% CI, 0.75-0.9) decreased significantly, while the risks for lichen planus (HR = 1.56; 95% CI, 1.22-1.99) and diabetes (HR = 1.14; 95% CI, 1.08-1.2) increased significantly.

Finally, the researchers restricted analysis to treated patients and found that patients who achieved SVR had a lower risk for mixed cryoglobulinemia (HR = 0.55; 95% CI, 0.33-0.9), glomerulonephritis (HR = 0.75; 95% CI, 0.57-0.99), PCT (HR = 0.31; 95% CI, 0.14-0.65) and diabetes (HR = 0.72; 95% CI, 0.65-0.78) compared with those without SVR.

The researchers observed gradual reductions in significance of antiviral treatment with increasing time from HCV index date for glomerulonephritis, NHL and stroke. Antiviral therapy showed the most significant protection when initiated at 1 or 2 years after HCV index date for glomerulonephritis and stroke, and at 1 year for NHL.

“These findings further strengthen the epidemiological evidence for [extrahepatic manifestations’] association with HCV infection,” the researchers concluded. “HCV-related [extrahepatic manifestations] carry a significant economic burden due to direct medical costs and indirect costs due to loss of productivity. The results of our study emphasize the extrahepatic benefits of SVR.” – by Talitha Bennett

Disclosure: Mahale reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.