C Special Treatment Considerations

1. Acute HCV—In a small study of 60 patients with acute hepatitis C, 85% of whom presented with symptomatic disease, treatment with interferon alone or in combination with ribavirin was begun immediately upon diagnosis in 6 patients. Of the 54 who were not treated, 37 (68%) cleared HCV spontaneously within a mean of 8 weeks after diagnosis; 13 relapsed later, leaving 24 (44%) persistently HCV RNA-negative. Although the numbers are small and should be interpreted with caution, none of the nine patients with asymptomatic acute hepatitis C cleared HCV RNA spontaneously, whereas 52% of those with symptomatic disease lost virus spontaneously, all within 12 weeks. Treatment given to those who did not recover spontaneously, beginning 3-6 months after onset of disease, led to SVR in 81%. Based on these results, the authors recommended delaying treatment 2-4 months after acute onset of acute hepatitis C to allow for spontaneous resolution. Others have presented evidence to show that earlier treatment (within 8 weeks) is superior in efficacy to treatment delayed thereafter. What is reassuring is that most studies of antiviral therapy demonstrate a very high frequency of viral clearance when therapy is administered within the first 3 months after diagnosis; although earlier trials involved high-dose interferon, subsequent trials suggest that a 6-month course of PEG IFNa plus ribavirin yields the same high SVR rate. Additional studies are underway.

2.  Renal disease—Historically, persons with renal disease have been at increased risk of acquiring HCV, predominantly through blood transfusions and exposure to HCV-contaminated equipment during hemodialysis. Ribavirin is contraindicated in this population because the drug is not removed during conventional dialysis, and its accumulation causes a dose-dependent hemolytic anemia. Treatment of patients with mild to moderate impairment in renal function must be individualized; however, ribavirin is not recommended in persons with creatinine clearance of less than 50 mL/min. Consequently, therapy for patients with substantial renal impairment or on hemodialysis should be PEG IFNa monotherapy at a reduced dose with close monitoring for interferon toxicity.

3.  Decompensated cirrhosis—Currently, interferon-based antiviral therapy is not recommended for patients with decompensated cirrhosis (ie, patients with one or more clinical complications of chronic liver disease, such as ascites, encephalopathy, variceal bleeding, coagulopathy, or hepatorenal syndrome). Instead, liver transplantation is the treatment of choice for such patients.

In patients with decompensated cirrhosis, antiviral therapy can be complicated by an increased risk of life-threatening infections as well as accelerating hepatic decompensation. Reinfection of the donor liver allograff with HCV is almost assured, and progressive post-transplantation disease of the allograft is common. Eradication of the virus prior to transplantation is associated with a low likelihood of posttransplantation infection, providing a strong incentive to treat HCV infection before transplantation; however, treating someone with decompensated liver disease is not recommended routinely, can be associated with substantial treatment intolerability, and should be done only in specialized centers. In addition, even in patients with short-term absence of HCV RNA post-transplantation, the virus is likely to become apparent again after longer follow-up monitoring. If such pretreatment antiviral therapy is initiated, low doses should be used initially and only in patients with mild degrees of hepatic compromise, with vigilant monitoring for adverse events, preferably in those who have already been accepted as candidates for liver transplantation.

Antiviral therapy for hepatitis C is indicated definitively in patients with compensated HCV-related cirrhosis who also have sufficient platelet and white blood cell counts to tolerate therapy.

4.  Post-solid organ transplantation—Immunosuppression administered to prevent allograft rejection plays a role in the accelerated liver disease observed in HCV-infected patients following transplantation. Interferon has been reported to precipitate rejection of kidney grafts; thus, the absence of clear treatment benefit and the concern about precipitating rejection mitigate against treating HCV infection in heart, lung, or kidney allograft recipients. The risk of precipitating rejection with interferon in liver allograft recipients appears to be low. Because, typically, HCV-related liver disease is this group is more progressive than that observed in immunologically competent persons, in most liver transplantation centers, antiviral therapy—its limitations and tolerability issues notwithstanding—is instituted once recurrent disease is established.

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