23 Feb Off
Increasingly, PACE programs are being confronted with the issue of whether or not to treat participants who have Hepatitis C with the newer Direct Acting Antiviral Agents (DAA’s). The cost of these drugs are so exorbitant that their use (among other factors) is causing PACE programs to pause and ask, “What should we do?” This month, we will discuss Hepatitis C (HVC) as a disease entity; in next month’s newsletter we will discuss appropriate treatment options for HCV in the PACE setting.
HVC is a chronic indolent infection: 15% of those infected will clear the acute infection. However, 85% will go on to have chronic disease. What is disconcerting is that 50% of those chronically infected with the virus have no idea that indeed they are. Often, if symptoms do develop they are extra-hepatic manifestations of the disease including mixed cryoglobulinemia, chronic kidney disease (membranoproliferative glomerulonephritis), and cutaneous manifestations such as leukocytoclastic angiitis. What is interesting is that Hepatitis C is not cytopathic to hepatocytes or other cells in which it resides. Rather, the fibrosis and cirrhosis seen is in response to cytokine induced stimulation of the stellate cells resulting in connective tissue deposition leading fibrosis and eventuallly cirrhosis.
Genotype 1 is the most common seen in the United States, and, before the advent of Direct Acting Antiviral Agents (DAA’s), was the most difficult to treat. Type 3 is associated with a tendency to more aggressive fibrosis deposition.
As mentioned, for those who develop chronic Hepatitis C, it pursues an indolent course. Natural history is hard to define. 15% or so will have spontaneous resolution, but these are typically mothers and young infants – not typically the type of participants seen in PACE. Only 60-70% develop chronic liver disease, and only 5-20% develop hepatic cirrhosis over a 20-30 year period of time. Even then only 5% of those initially infected go on to die from complications of the infection including Cirrhosis and Hepatocellular Carcinoma (HCC). In a meta-analysis, only 17% of people infected develop cirrhosis after 20 years post-exposure.
Even once cirrhosis develops the rate of progression to decompensated cirrhosis (e.g. ascites, variceal bleeding, and encephalopathy) is approximately 4% per year! Those participants who have compensated cirrhosis have a 79% survival rate ten years from diagnosis of cirrhosis (not from Hepatitis C infection).
As will be discussed in future newsletter, many treatment recommendations are based on the degree of fibrosis present and if it is advanced, is the cirrhosis detected compensated or uncompensated cirrhosis. Therefore, assessing degree of fibrosis in the liver of an infected participant is important. This can be accomplished by serologic determinations (Fibrotest® as one example), sonographic techniques (Ultrasound Based Transient Elastography), or by the more invasive liver biopsy. All have their advantages and drawbacks.
Once cirrhosis has been documented, though, there are still further ways to further assess the prognosis of an infected participant. These include, among others, the Child-Trucotte-Pugh Score. This is a simple scoring system predicts mortality rates by the degree of advanced cirrhosis as measured by the presence of ascites, bilirubin, albumin, Prothrombin time and degree of encephalopathy.. Furthermore, these parameters can help define those participants with compensated versus uncompensated cirrhosis, which, in many practice guidelines, helps define those with HCV who should be treated and those in whom watchful waiting may be a more prudent idea.
What is now cutting edge is this: if a sustained virologic response (SVR) is an indication – which it likely is – of cure of HVC, then it appears that the new Directly Acting Antiviral Agents (DAA’s) might be curative therapy. However, the larger question is whether a PACE participant with HCV should be treated. That, indeed, is a more complicated question and one that will need to wait until next month for an answer.