HCV Replicate Outside the Body

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Does HCV Replicate Outside The Liver and It’s Significance?
Reported by Jules Levin

Some individuals with HCV report experiencing fatigue, emotional distress, and cognitive impairment. Objective testing has found HCV can be associated with these symptoms. Some doctors believe these symptoms may be associated with causes other than HCV, such as prior alcohol or drug use, or other psychiatric disturbances; and some studies suggest HCV can enter the CSF and the brain. In HIV, it has been established that HIV can reside and replicate in the brain. Another way in which HIV or HCV may affect the brain is by disturbances caused to the immune system, disruptions in cytokine balance. Disruptions in the immune system can affect the brain and other organs. So, can HCV reside and replicate in other organs other than the liver? This question is the subject of previously reported and ongoing studies. This article reports on previous study findings and tries to put these questions in perspective.

Two studies reported at AASLD (Nov 2002) discuss HCV and it’s possible presence in the brain suggesting implications for the presence of HCV extra-hepatically, outside the liver. Results from study in England suggests HCV replicates in the brain (abstract 185, Forton et al). Researchers at the Mayo Clinic reported finding HCV in the cerebrospinal fluid and in PBMCs of patients with HCV in serum, suggesting the PBMCs may carry HCV into the neurologic system; this study is detailed at http://www.natap.org/2002/AASLD/day15.htm

So, does HCV replicate and is it found outside the liver? Results are mixed from various studies conducted over recent years, and some of these studies are reported below. Apparently, this question has not been answered and whether HCV exists outside the liver is not resolved. In fact, there are enough reasons to think HCV may not reside in reservoirs outside the liver as there are to think there are reservoirs outside the liver. The first article below talks about extrahepatic manifestations of HCV. It is clear that patients with HCV experience skin, renal, hematologic, and arthritic disorders, and having these disorders is associated with having HCV. The study is one of many supporting this and it is well accepted that HCV is associated with these extrahepatic disorders. However, it is distinctly possible that this is due to HCV causing cytokine disruptions, dysregulation in the immune system, which may in turn lead to these disorders; rather thah due to HCV replicating in cells and organs outside the liver. Apparently, the studies that have found HCV in cells and organs outside the liver use lab testing methods and techniques which are not yet refined enough to be completely accepted by researchers. It appears researchers feel these test methods need further evaluation and confirmation.

In the end, it appears unresolved whether HCV can replicate or exists outside the liver. In addition, it may be irrelevant even if it does replicate and exist outside the liver. In HIV, reservoirs have been identified in patients who achieve and sustain undetectable HIV viral load (<50 copies/ml of HIV viral load). In addition, these patients can sustain undetectability and maintain good health for many years despite these reservoirs. It remains unanswered whether these patients will see their HIV viral load rebound due to the existence of reservoirs. So, does the existence of HCV reservoirs matter, if they do exist? Perhaps not. Studies of patients with HCV who have sustained viral responses for as long as 11 years have found no HCV in the blood or liver. Presumably, if HCV reservoirs persist these individuals would have reservoirs. Yet these patients remained undetectable. If HCV reservoirs do in fact exist, perhaps achieving sustained response eradicates HCV in these reservoirs. Perhaps patients who relapse after achieving end-of-treatment responses from IFN/RBV do so because there are reservoirs. These questions remained unanswered. But, ultimately what appears to matter is whether or not a patient can achieve and sustain a sustained viral response. If they can, studies show no HCV in the blood and liver. Of course, we do in fact need long term and larger studies to confirm that SVRs are sustainable and to evaluate the long term health outcomes for patients who sustain the SVR.

Extrahepatic manifestations of hepatitis C among United States male veterans

Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, we carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816) matched with cases on the year of admission. The inpatient and outpatient files were searched for several disorders involving the skin (porphyria cutanea tarda [PCT], vitiligo, and lichen planus); renal (membranous glomerulonephritis [GN] and membranoproliferative glomerulonephritis); hematologic (cryoglobulin, Hodgkin's and non-Hodgkin's lymphoma [NHL]); endocrine (diabetes, thyroiditis); and rheumatologic (Sjögren's syndrome). The association between HCV and these disorders was examined in multivariate analyses that controlled for age, gender, ethnicity, and period of military service. Patients in the case group were younger in age (45 vs. 57 years), were more frequently nonwhite (39.6% vs. 26.3%), and were more frequently male (98.1% vs. 97.0%). A significantly greater proportion of HCV-infected patients had PCT, vitiligo, lichen planus, and cryoglobulinemia. There was a greater prevalence of membranoproliferative GN among patients with HCV but not membranous GN. There was no significant difference in the prevalence of thyroiditis, Sjögren's syndrome, or Hodgkin's or NHL. However, NHL became significant after age adjustment. Diabetes was more prevalent in controls than cases, but no statistically significant association was found after adjustment for age. In conclusion, we found a significant association between HCV infection and PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN, and NHL. Patients presenting with these disorders should be tested for HCV infection. (HEPATOLOGY 2002;36:1439-1445.)

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