Assessment of liver disease
This section details SIGN's recommendations on the use of clinical assessments, fibrosis markers and liver biopsies for patients with hepatitis C.
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Clinical assesment
Clinical assessment of the severity of liver disease in patients with chronic hepatitis C is inaccurate and tends to underestimate the severity of change seen on liver biopsy. 73 3
Fibrosis markers
Studies of non-invasive prediction of the severity of liver disease using combinations of clinical and biochemical scores have found that it may be possible to distinguish patients with cirrhosis from those with mild disease. Intermediate stages are not distinguishable. 74 2++
A systematic review demonstrated that surrogate markers of fibrosis either reflecting disordered liver function (alanine aminotransferase, platelets) or fibrosis metabolism (eg tissue inhibitor of matrix metalloproteinase 1, hyaluronic acid) cannot be used individually to predict fibrosis. In individual patients such markers used alone cannot differentiate the stage of fibrosis reliably. Used in panels they are able to determine whether an individual has high or low levels of fibrosis. The 14 studies in the systematic review used 10 different panels of markers, none of which was superior to any other in statistical comparisons. The tests were compared against the gold standard of liver biopsy as part of their validation, though liver biopsy may potentially be inaccurate due to sampling error. Comparison of surrogate markers and liver biopsy to clinical outcomes would be more relevant. 752++
Other methods for assessing liver fibrosis, such as measuring liver stiffness, show promise in pilot studies. 76, 77
Biochemical markers should not be used as an alternative to liver biopsy for staging of intermediate grades of fibrosis.
Biochemical tests may be used as an alternative to liver biopsy to diagnose cirrhosis or to direct screening for complications of fibrosis.
Liver biopsy
Liver biopsy needs to be at least 25 mm long in order to report stage of fibrosis with 75% accuracy. 78 The mortality of liver biopsy is between 0.13-0.33% and the rate of significant morbidity is about 5.9%. 79 3
When to biopsy
Liver biopsy of patients with CHC infection can reveal additional diagnoses such as alcoholic liver disease or steatosis (10% patients) and may influence management decisions in 5% of patients. 80 Repeat liver biopsies may be useful for the identification of individuals for treatment; one third of patients with mild CHC show one stage of fibrosis progression on the Ishak scale (0-6) at a median of 30 months. 81 The frequency and timing of liver biopsy should be tailored to individual patients as progression of fibrosis is non-linear. 3
Advanced fibrosis or cirrhosis on liver biopsy compared with milder disease predicts a modest reduction in SVR after antiviral therapy. 82 1++
Liver biopsy before and after successful antiviral therapy (median 20 months interval) has shown both improvement in fibrosis (277 out of 1,094 patients) and downgrading of stage in cirrhosis (75 out of 153 patients). 83 1+
Liver biopsy should be performed if there is concern about additional causes of liver disease.
Repeat liver biopsies should be considered in patients with mild disease who remain untreated, if progression of liver fibrosis would influence the decision to opt for antiviral therapy.
Good practice points
In patients with congenital bleeding disorders liver biopsy should be performed in consultation with a haemophilia specialist.
Biopsy and Genotype
The sustained viral response rate after pegylated IFN and ribavirin therapy for patients with genotype 2 and 3 infection is 76-82% and 41-51% for patients with genotype 1 infection. 7 The UK Health Technology Assessment Centre has recommended that pre-treatment liver biopsy in patients with genotype 2 and 3 infection may not be required. 7 4
Liver biopsy should not be considered an essential test prior to using antiviral therapy, especially in patients with genotype 2 and 3 disease.
