NCCC Clinical Pearls: Fibrosis Matters

Patients with chronic hepatitis C (CHC) should receive treatment with directly acting antivirals (DAAs) regardless of fibrosis stage. But does that mean that fibrosis is irrelevant? Absolutely not. Fibrosis remains a central concept in the care of patients with chronic liver disease, and patients with a history of hepatitis C virus (HCV) are no exception.

Fibrosis, or scarring, in the liver, varies from nil to complete. Importantly, regression of fibrosis is possible in some cases with treatment of the underlying process. The most typically used Metavir scale ranges from 0 (the normal absence of scarring) to 4 (cirrhosis or complete occupation of the organ with fibrosis). Fibrosis stage is significant for prognosis, as cirrhosis brings with it the risk of life-threatening complications like ascites, encephalopathy, variceal hemorrhage, and hepatocellular carcinoma. These are the decompensation events that herald end-stage liver disease and prompt consideration of liver transplantation. Of note, patients with HIV-HCV coinfection tend to have more rapid progression of fibrosis and higher rates of hepatic decompensation than mono-infected patients with CHC.

However, CHC patients with minimal fibrosis also warrant HCV treatment. During the interferon era and early days of DAA availability, we prioritized patients with significant or advanced fibrosis. Now, it is clear that the treatment of patients with minimal fibrosis yields significant benefits in mortality and progress toward HCV eradication.

Fibrosis staging helps the clinician select the correct DAA regimen for a given patient with CHC. For instance, patients with compensated cirrhosis who will receive sofosbuvir/velpatasvir, need genotype testing to determine if ribavirin must be added to their treatment regimen (i.e. if they have genotype 3). Patients with decompensated cirrhosis frequently require stronger and longer treatment regimens. These considerations are the same for people with HIV as they are for those without.

Although fibrosis staging can be a complex and challenging process, the AASLD and IDSA have simplified the process for the purposes of HCV treatment. They recommend calculating the FIB-4 score, which requires entering the patient’s age, platelet count, AST, and ALT into a formula. In addition, the provider must look at the patient’s previous data, including prior fibrosis assessments such as liver biopsy, elastography, or proprietary send-out tests like FibroSure. Finally, clinical evidence of cirrhosis should be considered, e.g. history of variceal hemorrhage, physical exam findings of cirrhosis such as spider angiomata, laboratory findings like thrombocytopenia, or imaging findings of a nodular liver contour.

HCV treatment providers should also recognize that the fibrosis assessment influences the broader management of the patient. Beyond HCV treatment regimen selection, fibrosis stage has implications for monitoring (liver function), referral (to a subspecialist or transplant center), screening (HCC, varices) and health care maintenance (vaccines, bone density, etc.).

For people with both HCV and HIV co-infection, knowing the fibrosis stage can impact HIV antiretroviral regimen selection as well.  Current guidelines recommend that abacavir (ABC), for example, be given at a lower dose for people with mild hepatic impairment, including those with compensated cirrhosis/Child-Pugh class A, and that it be avoided altogether in those with more advanced hepatic impairment (Child-Pugh B or C). Other commonly used medications like dolutegravir, tenofovir alafenamide/emtricitabine/bictegravir and boosted darunavir are considered safe to use in people with mild hepatic impairment but should be avoided in those with frankly decompensated liver disease (Child-Pugh C).

In summary, while the ease and efficacy of DAA treatment has vastly changed and improved the landscape of CHC management, fibrosis still matters.

Key Points

  • We should try to treat all patients with CHC regardless of fibrosis stage.
  • Fibrosis staging is important for prognosis and management.
    • People with HIV-HCV co-infection tend to progress to advanced fibrosis stages more rapidly than those with HCV mono-infection
  • Fibrosis stage can affect DAA regimen choice.
  • The AASLD and IDSA have developed a simplified process of assessing fibrosis for the purposes of HCV treatment.

Have a question about fibrosis management?
Call the Hepatitis C Warmline at (844) HEP‐INFO or (844) 437-4636 for free, clinician-to-clinician advice on hepatitis C mono-infection and co-infection management. Our clinicians are available Monday through Friday, 9:00 a.m. to 8:00 p.m. EST. Voice mail and online case submission are available 24 hours a day at

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