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HEPATITIS C GUIDANCE: AASLD-IDSA [IAS] RECOMMENDATIONS FOR TESTING,
MANAGING, AND TREATING ADULTS INFECTED WITH HEPATITIS C VIRUS
- (WHEN AND IN WHOM TO INITIATE HCV THERAPY) -
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Download the PDF here
Hepatology (accepted articles) Accepted manuscript online: 25 JUN 2015 08:25AM EST
Authors On behalf of the Hepatitis C Guidance Panel (see AASLD/IDSA HCV GUIDANCE PANEL MEMBERS AND AUTHORS)
In 2013, the two major membership societies supporting liver and infectious diseases specialists (AASLD and IDSA) joined forces to develop guidance for the management of hepatitis C in this rapidly moving field. The International Antiviral Society-USA (IAS-USA), which has experience in developing treatment guidelines in HIV disease, was invited to join the effort as a collaborating partner responsible for managing the Panel and the Guidance development process.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record
These recommendations have been approved by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA).
"HIV/HCV COINFECTION: with the advent of DAAs, differences
in treatment responses between mono- and coinfected patients have not been detected [115,116]. Thus, the same HCV treatment recommendations for HIV/HCV coinfected persons as for those with just HCV infection, with consideration of potential drug-drug interactions with HIV medications." (see pdf attached for full discussion/treatment recommendations)
WHEN AND IN WHOM TO INITIATE HCV THERAPY
Successful hepatitis C treatment is achievable in nearly all infected patients and is reflected by a sustained virologic response (SVR), defined as the continued absence of detectable HCV RNA for 12 or more weeks after completion of therapy. SVR is a marker for virologic cure of HCV infection and has been shown to be durable in large prospective studies in more than 99% of patients followed up for at least 5 years [39,40]. Patients who are cured of their HCV infection experience numerous health benefits, including a decrease in liver inflammation, regression of fibrosis in most cases, and resolution of cirrhosis in half [41]. Among the latter group, portal hypertension, splenomegaly, and other clinical manifestations of advanced liver disease also improve. SVR is associated with a more than 70% reduction in the risk of liver cancer (hepatocellular carcinoma [HCC]) and a 90% reduction in the risk of liver-related mortality and liver transplantation [42-44].
Cure of HCV infection may also reduce symptoms and mortality from severe extrahepatic manifestations, including cryoglobulinemic vasculitis, a condition affecting up to 15% of HCV-infected individuals [45,46]. HCV-infected persons with non-Hodgkin lymphoma and other lymphoproliferative disorders achieve complete or partial remission in up to 75% of cases following successful HCV treatment [47-51]. These reductions in disease severity contribute to dramatic reductions in all-cause mortality [43,52]. Lastly, patients achieving SVR have substantially improved quality of life, including physical, emotional, and social health [53,54].
Evidence clearly supports treatment for all HCV-infected persons, except those with limited life expectancy (less than 12 months) due to nonŠliver-related comorbid conditions. Although treatment is best administered early in the course of the disease before fibrosis progression and the development of complications, the most immediate benefits of treatment will be realized by populations at highest risk for liver-related complications. Thus, where resources limit the ability to treat all infected patients immediately as recommended, it is most appropriate to treat first those at greatest risk of disease complications, and those at risk for transmitting HCV or in whom treatment may reduce transmission risk. Where such limitations exist, prioritization of immediate treatment for those listed in Tables 3 and 4 is recommended, including patients with progressive liver disease (Metavir stage F3 or F4), transplant recipients, or those with clinically severe extrahepatic manifestations.
Recent reports suggest that initiating therapy in patients with lower stage fibrosis may extend the benefits of SVR. In a long-term follow-up study, 820 patients with Metavir stage F0 or F1 fibrosis confirmed by biopsy were followed for more than 20 years. The 15-year survival rate was significantly better in those who experienced an SVR than in those whose treatment had failed or those who were untreated (93%, 82% , and 88%, respectively; P=.003) and argues for consideration of earlier initiation of treatment [55]. Several other modeling studies suggest greater mortality benefit if treatment is initiated at stages prior to F3 [56-58].
Recommendation:
6. Antiviral treatment is recommended for all patients with chronic HCV infection, except those with limited life expectancy due to nonhepatic causes.
(I-A)
Recommendation:
7. If resources limit the ability to treat all infected patients immediately as recommended, then it is most appropriate to treat those at greatest risk of disease complications before
treating those with less advanced disease. (See Tables 3 and 4 for ratings).
An accurate assessment of fibrosis is vital in assessing the urgency for treatment, in some
instances the duration of treatment, and the need for more intensive clinical monitoring. The degree of hepatic fibrosis is one of the most robust prognostic factors used to predict disease progression and clinical outcomes [59]. In addition to being in more urgent need for antiviral therapy, individuals with severe fibrosis require screening for hepatocellular carcinoma (HCC) and esophageal varices [60,61].
There are several acceptable approaches to staging. Individuals with clinically apparent cirrhosis such as those with endoscopic evidence of varices or imaging showing cirrhosis or portal hypertension do not require additional staging. However, the majority of patients require testing to determine stage. Although liver biopsy is the diagnostic standard, sampling error and observer variability limit test performance, particularly when inadequate sampling occurs [62]. In addition, the test is invasive and minor complications are common, limiting patient and practitioner acceptance. Serious complications such as bleeding, although rare, are well recognized. Recently, noninvasive tests to stage the degree of fibrosis in patients with chronic HCV infection include models incorporating indirect serum biomarkers (routine tests such as aspartate transaminase [AST], alanine transaminase [ALT] and platelet count), direct serum biomarkers (components of the extracellular matrix produced by activated hepatic stellate cells), and vibration-controlled transient liver elastography [63-66]. No single method is recognized to have high accuracy alone and results of each test must be interpreted carefully. The most efficient approach to fibrosis assessment is to combine direct biomarkers and vibration-controlled transient liver elastography [67].
Recommendation:
8. Use of noninvasive testing or liver biopsy is recommended in order to assess the degree of hepatic fibrosis, and hence the urgency of immediate treatment. (I-A)
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