Background and Prevalence
Although hepatitis C virus (HCV) infection primarily affects the liver, other organ systems can become involved, which may result in a variety of clinical complications, including cryoglobulinemia, renal disease, dermatologic disorders, diabetes, and lymphomas (Figure 1).[1,2,3,4,5] The HCV-associated extrahepatic manifestations can have a major impact on morbidity, mortality, and medical costs.[6,7,8,9] The percentage of persons with chronic HCV infection who develop some extrahepatic manifestation remains poorly defined. Nevertheless, some experts have estimated that up to 38% of persons with HCV will develop at least one extrahepatic manifestation at some point.[10]
Need for Recognition
It is extremely important that clinicians consider the potential for HCV to cause extrahepatic manifestations in persons with chronic HCV infection (Figure 2). It is unclear how well clinicians recognize, diagnose, and treat such extrahepatic conditions, especially since many individuals with HCV infection may not have obvious manifestations of chronic liver disease and often have undiagnosed HCV infection. An awareness of the range of potential extrahepatic manifestations could facilitate earlier diagnosis and more appropriate and timely treatment of these disorders.
Quality of Evidence
Most of the literature on HCV-related extrahepatic manifestations consists of observational studies that have shown an association between a specific extrahepatic condition and the presence of HCV antibody and/or detection of HCV RNA. Most of these studies are prone to selection bias. A few studies have used large datasets, such as the Veterans Administration medical database, and these studies are most useful when the extrahepatic condition in question can be easily defined and the data is easily accessible (e.g., renal disease as determined by a creatinine level or glomerular filtration rate [GFR]).[11,12,13] For extrahepatic conditions that require a clinical diagnosis, such as lichen planus, identifying the specific condition is much more difficult when utilizing larger datasets.[14,15] Thus, it is important to keep in mind the original source and type of data when estimating prevalence of these extrahepatic conditions and considering the need for screening.
Relevance to Initiating DAA Therapy
The diagnosis of any extrahepatic HCV conditions necessitates urgent initiation of direct-acting antiviral (DAA) treatment of HCV, unless the person with HCV has already received successful treatment. Although both public plans and commercial policies regarding approval for HCV treatment are constantly changing, these payers typically cover DAA therapies when any extrahepatic manifestation exists, despite level of hepatic fibrosis.