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A painless alternative to liver biopsy for evaluating the stage of liver  fibrosis.
Jan
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Also includes information on about Magnetic  Resonance Elastography, or MRE which is an non-invastive test for liver
fibrosis.

Is there still a role for liver  biopsy in managing hepatitis C virus infections?

Clinical Liver Disease  Volume 1,  Issue  2, pages  32–35, April  2012

1. Syed-Mohammed R. Jafri M.D.*, 
2. Stuart C. Gordon M.D.

Article first published online: 26 APR 2012
DOI: 10.1002/cld.30

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Abstract
A2M, alpha-2-macroglobulin; ALT, alanine aminotransferase; AST, aspartate  aminotransferase; BOC44, boceprevir for 44 weeks; BOC RGT, boceprevir and  response-guided therapy; CDS, cirrhosis discriminant score; DAA, direct-acting antiviral; GGT, gamma-glutamyl transpeptidase; HA, hyaluronic acid; INR, international normalized ratio; ITT, intention to treat; Pbo, placebo; PIIINP, amino-terminal propeptide of type III collagen; PR48, peginterferon/ribavirin  for 48 weeks; SVR, sustained virological response; T12PR, telaprevir for 12  weeks and peginterferon/ribavirin; T12/PR48, telaprevir for 12 weeks and   peginterferon/ribavirin for 48 weeks; TIMP1, tissue inhibitor of  metalloproteinase 1.
 
Current guidelines emphasize the importance of liver biopsy in the management of patients with hepatitis C because liver histology provides patients and their  physicians with important prognostic information and helps to guide therapy  decisions and treatment regimens.1,2 Recent improvements in  antiviral therapy along with the development of alternate modes of evaluating  fibrosis have led to a global reassessment of the risks and benefits and the  overall wisdom of performing liver biopsy in these patients.
 
The presence of advanced or worsening fibrosis has traditionally served as an unequivocal indication for therapy,3 and clinicians still use the  degree of fibrosis as a means for justifying therapy sooner rather than later.  The availability of
direct-acting antiviral (DAA) agents, which bring the  promise of rapid viral negativity with therapy, intuitively appears to lessen  the need for biopsy in therapeutic decision making; this is analogous to  previously held perceptions about genotype 2/3 patients, who had higher  sustained virological response (SVR) rates. Because of the increased efficacy of  the newer regimens and even better regimens around the corner, clinicians and  patients may choose to forgo biopsy with the compelling argument that the  benefits of such effective therapy justify its use, even in those with minimal  disease.
 
On the basis of the results of pivotal registration trials, the US Food and Drug Administration has suggested that therapy with DAA agents mandates an assessment of the degree of fibrosis because of the vastly different therapeutic  regimens for patients with more advanced fibrosis. The recommended treatment  with peginterferon/ribavirin and either telaprevir or boceprevir must be longer  (48 weeks) because of the consistently lower efficacy of the therapy in patients  with cirrhosis2  (Figs. 1–3).
Accordingly, an assessment of the  degree of fibrosis is crucial before the initiation of therapy. Treatment with  interferon and ribavirin has led to higher rates of adverse events, including  anemia, in the face of cirrhosis,8,9 and this information must  be discussed with patients with cirrhosis before the initiation of current  DAA-based therapies that include peginterferon and
ribavirin.

Figure 1. SVR rates by the degree of fibrosis in the  ADVANCE and ILLUMINATE studies. Abbreviations: ITT, intention to treat; PR48, peginterferon/ribavirin for 48 weeks; T12PR, telaprevir for 12 weeks and peginterferon/ribavirin.
Adapted with permission from New England Journal 
of Medicine.4, 5

Figure 3. SVR rates by the degree of fibrosis in the  REALIZE trial. Abbreviations: Pbo, placebo; PR48, peginterferon/ribavirin for 48  weeks; T12/PR48, telaprevir for 12 weeks and peginterferon/ribavirin for 48 weeks. Adapted with permission from the European Association for the Study of  the Liver.7

In comparison with peginterferon/ribavirin dual therapy, the telaprevir- and boceprevir-based regimens have superior
efficacy,4,10-14 but the field is  moving forward quite rapidly, and we are currently learning about (1) far more  potent DAA agents with better pharmacokinetic profiles, (2) interferon-sparing  regiments, and (3) SVR rates approaching 100%. Thus, there is the likelihood  that superior regimens will become available over the next few years. As  physicians and patients with hepatitis C virus ponder their options, information  obtained from liver biopsy samples may greatly assist in the decision to wait  yet longer for future regimens with improved efficacy, shorter durations, and  lower side-effect profiles.

 
The establishment of the fibrosis stage remains a key parameter that guides the management of patients with chronic hepatitis C. The presence of advanced fibrosis requires future lifelong screening for the development of varices and hepatocellular carcinoma, regardless of future responses to antiviral therapy. 

Unfortunately, an all-too-common scenario in clinical practice is the patient  with known or unknown hepatitis C who learns of his cirrhosis only after the discovery of liver cancer or a large variceal bleed. Advanced fibrosis may exist  in patients with normal liver enzyme levels and synthetic parameters.15 

The  identification of fibrosis at biopsy can be used as a realistic justification  for encouraging reduced alcohol intake and weight reduction, which are factors  that would otherwise accelerate the progression to cirrhosis.16-21

For the post–liver transplant patient with chronic hepatitis C, liver biopsy information is essential not only for assessing patients for fibrosis but also for differentiating between recurrent hepatitis C–induced inflammation and acute  cellular rejection. Accelerated fibrosis progression in the posttransplant  patient with chronic hepatitis C leads to graft loss in up to 30% of infected  patients.22-24 

Preemptive antiviral therapy without the  guidance of biopsy information is often precluded by cytopenias, renal  insufficiency, increased side effects, and the possibility of rejection.25,26 Current  guidelines suggest the initiation of therapy only after the demonstration of  significant cholestasis or fibrosis on liver biopsy.1,27 Accordingly, the  information gained from liver biopsy, including the demonstration of either  fibrosis progression or a lack of rejection, before the institution of antiviral  therapy is vital to the posttransplant care of the hepatitis C  patient.
 
The risks of liver biopsy include severe pain, organ perforation, and bleeding.28,29 This potential for complications has  generated an increasing acceptance of alternative assessments of hepatic  fibrosis, especially in patients with hepatitis C (Table 1). 

Unfortunately, for many such panels, availability, third-party payment, or widespread clinical consensus is lacking. Fibrosis related to chronic hepatitis C progresses slowly (on average 0.15 stages per year30), and a feasible  alternative to liver biopsy must be able to measure this progression over time.  Evaluations using standard laboratory tests, including the aspartate  aminotransferase/alanine aminotransferase ratio, the cirrhosis discriminant  score, the age-platelet index, the Pohl score, the aspartate aminotransferase to  platelet ratio index, and platelet counts, lack either the sensitivity or the  specificity needed to be useful in clinical practice.31,34,35 In addition, these  noninvasive fibrosis markers may have reduced performance in
hepatitis C  patients with normal alanine aminotransferase levels.36 Larger test panels,  including Hepascore, Liverscore, and FibroTest, have high potential for  false-positive results and are not readily available in clinical practice.32,37-39 These  laboratory tests and panels have not reliably detected intermediate stages of  fibrosis or the progression of fibrosis, and this is valuable information for  clinical decision making.30,40 Transient elastography  produces suboptimal results in obese patients and in tracking changes in  fibrosis.41-43 The reproducibility of transient elastography  is significantly reduced (P < 0.05) in patients with steatosis, an  increased body mass index, or lower degrees of hepatic fibrosis.

Percutaneous liver biopsy