Retinal vein thrombosis associated with pegylated-interferon and ribavirin combination therapy for chronic hepatitis C

Abstract

An estimated 300 million people worldwide suffer from chronic hepatitis C with a prevalence of 0.8%-1.0% of the general population in Canada. An increasing pool of evidence exists supporting the use of pegylatedinterferon (pegIFN) and ribavirin combination therapy for hepatitis C. We report a 49-year old male of North American aboriginal descent with chronic hepatitis C (genotype 2b). Biopsy confirmed that he had cirrhosis with a 2-wk history of left eye pain and decreased visual acuity. He developed retinal vein thrombosis after 16 of 24 wk of pegIFN-a 2a and ribavirin combination therapy. He was urgently referred to a retinal specialist and diagnosed with non-ischemic central retinal vein occlusion of the left eye. PegIFN and ribavirin combination therapy was discontinued and HCV RNA was undetectable after 16 wk of treatment. Hematologic investigations revealed that the patient was a factor V Leiden heterozygote with mildly decreased protein C activity. Our patient had a number of hypercoagulable risk factors, including factor V Leiden heterozygosity, cirrhosis, and hepatitis C that alone would have most likely remained clinically silent. We speculate that in the setting of pegIFN treatment, these risk factors may coalesce and cause the retinal vein thrombosis.

Ocular side effects of antirheumatic medications: a qualitative review

“…Case reports of episcleritis are associated with interferon alpha-2b in the treatment of head and neck mucosal melanoma 106. There are also reports of non-arteritic anterior ischaemic optic neuropathy, neuromyelitis optica, optic neuritis, retinopathy, cystoid macular oedema, Vogt–Koyanagi–Harada disease, abducens palsy, oculomotor nerve palsy, glaucoma and retinal vein thrombosis reported in patients treated with interferon alpha 107–129…”

Trombosis venosa retiniana asociada a peginterferón alfa 2b más ribavirina en un paciente con hepatitis C crónica

“…desequilibrio entre los factores procoagulantes y anticoagulantes. Este desequilibrio es el causante de un estado de hipercoagulabilidad que, unido a la terapia con IFN-alfa o con la combinación de IFN-alfa y ribavirina en pacientes con hepatitis viral, parece ser el principal causante de la trombosis de la vena de retina 3,[5][6][7][8] . Además, la propia hepatitis también ha sido relacionada con la producción de anticuerpos trombogénicos 5 .…”

“…En general, los pacientes referenciados en la literatura médica presentaban un estado avanzado de la enfermedad (cirrosis) y, además, mutaciones genéticas (del factor V de Leiden, gen de la protrombina) u otros factores predisponentes a estados de hipercoagulabilidad (hiperlipidemias, diabetes mellitus o fumadores) 3,[5][6][7][8] .…”

“…Los anticuerpos antimúsculo liso no parecen estar relacionados directamente con eventos trombóticos, aunque sí se han asociado a la producción de otros anticuerpos trombogénicos, como los anticuerpos anticardiolipina 3 . Por otro lado, los valores bajos, pero no patológicos, de la proteína S no explican por sí solos la producción de un estado de hipercoagulabilidad pero, unidos al resto de los factores procoagulantes (hábito tabáquico, hepatitis viral y la terapia con IFN-alfa más ribavirina), pueden ser los causantes del desequilibrio en la coagulación del paciente, dando lugar a la oclusión de la vena retiniana [3][4][5][6][7][8] .…”

Venous Thromboembolism in Chronic Liver Disease

“…Although several case reports and small case series have documented venous thrombotic episodes in patients with advanced CLD, 41 especially if associated with inherited (i.e., prothrombotic gene mutations such as factor V Leiden or prothrombin G20210A) or acquired (i.e., antiphospholipid syndrome, antiviral treatment, or liver transplant) procoagulant risk factors, [42][43][44][45][46] it still remains uncertain whether the prolonged INR observed in these patients protects against venous thromboembolism (VTE). 47,48 Unfortunately, only a few studies have specifically addressed this issue.…”