Hepatitis C Virus-Associated Extrahepatic Manifestations in Lung and Heart and Antiviral Therapy-Related Cardiopulmonary Toxicity

Abstract

Besides liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations (EHMs). HCV exhibits lymphotropism that is responsible for various EHM. An important characteristic of HCV is escape from the immune system, which enables it to produce chronic infections and autoimmune disorders along with accumulation of circulating immune complexes. These EHMs have large spectrum, because they affect many organs such as heart, lungs, kidney, brain, thyroid, and skin. HCV-related cardiac and pulmonary manifestations include myocarditis, cardiomyopathies, cardiovascular diseases (i.e., Stroke, ischemic heart disease), chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and interstitial lung diseases. This review discusses etiology and pathogenesis of HCV-associated cardiac and pulmonary manifestations and how different genes, immune system, indirectly linked factors (mixed cryoglobulinemia), liver cirrhosis, and antiviral treatment are involved in HCV-related heart and lung diseases, however, their exact mechanism is not clear.

Cardiovascular Involvement in Chronic Hepatitis C Virus Infections – Insight from Novel Antiviral Therapies

“…The study is primarily based on noninvasive assessment (serial echocardiographies, HF biomarkers) to ascertain the frequency of combination of cardiomyopathy with HCV infection. In a subgroup of patients with advanced cardiac dysfunction 5 and/or or extensive morphological anomalies, right/left ventricular EMBs 68 – 70 are to be performed in accordance with ESC guidelines. 5 Patients are classified as IMPs if LVEF increases by 10 absolute percent units or if NYHA improves by one class.…”

“…In a subgroup of patients with advanced cardiac dysfunction 5 and/or or extensive morphological anomalies, right/left ventricular EMBs 68 – 70 are to be performed in accordance with ESC guidelines. 5 Patients are classified as IMPs if LVEF increases by 10 absolute percent units or if NYHA improves by one class. Patients are classified as NIMPs if they show at the follow-up visit any of the parameters such as an LVEF <35 %, failure to improve LVEF by 10 absolute units, remaining at a NYHA functional class of III/IV or obtaining heart transplantation/ventricular assist device or if patients die.…”

“…The study is primarily based on noninvasive functional assessment of patients (serial echocardiography, HF biomarkers) which allows to ascertain the frequency of the combination of cardiomyopathy with HCV infection, and to address the question of cardiovascular therapeutic impact. In a subgroup of patients with advanced cardiac dysfunction 17 – 22 and/or or extensive morphological anomalies (e.g., massive left/right ventricular hypertrophy), right/left ventricular EMBs 71 – 73 are to be performed in accordance with ESC guidelines EMBs, 5 providing molecular virological data, 4 , 37 , 38 immunohistological data and immune-related gene expression profiles to identify and characterize inflammation, and histology to detect storage diseases. In addition, cardiac autoantibody arrays 74 – 76 will be conducted immediately before and 6 months after HCV elimination.…”

“… 77 – 79 Virus infections induce an innate immune response not only when active viral replication takes place, but also in latent infections with even minimal viral synthesis of immunogenic nucleic acids or proteins. 5 , 80 , 81 In addition to this primordial innate immune activation, there may be virus-triggered autoantibody formation by molecular mimicry or other mechanisms. Second, it has been shown that DAA-induced HCV clearance does not completely restore the altered cytokine and chemokine milieu.…”

Remodeling of the Pulmonary Circulation in Patients with Viral Liver Cirrhosis

“…Данные о влиянии противовирусной терапии на сердечно-сосудистую систему противоречивы, так, в некоторых исследованиях установлено, что противовирусная терапия нивелировала структурно-функциональные отклонения сердечно-сосуди-стой системы [8,9]. В других исследованиях показано ее негативное влияние на сердце и легкие с развитием инсульта, ишемической болезни сердца, хронической обструктивной болезни легких, идиопатического легочного фиброза, астмы, однако механизмы данных нарушений до сих пор неизвестны [9,10].…”