liver biopsy
TRANSCRIPT
LIVER BIOPSY PREFERRED INVESTIGATION FOR DIAGNOSIS OF
INFLAMMATION AND STAGE OF FIBROSIS IN CHRONIC LIVER DISEASEMEHNAAZ SULTAN KHUROOCONSULTANT PATHOLOGIST
GOVERNMENT MEDICAL COLLEGE SRINAGAR, J&K
GLOBAL IMPACT OF LIVER DISEASELiver disease is a major cause of illness and death worldwideChronic liver disease and cirrhosis are important causes of morbidity and mortality in the world.
Globally, alcohol consumption, hepatitis B (HBV) and hepatitis C (HCV) have been the main causes of cirrhosis.
However, increasing prevalence of OBESITY and the METABOLIC SYNDROME has resulted in increasing incidence of cirrhosis secondary to non-alcoholic fatty liver disease (NAFLD), especially in developed countries.
Burden of chronic liver disease is projected to increase, due to, the increasing prevalence of end-stage liver disease and HCC secondary to NAFLD and HCV.
LIVER BIOPSY
Erlich is credited with the first liver aspiration in 1883
First percutaneous liver biopsy for diagnostic purposes was reported in 1923.
The technique has been modified since then.Over the past 50 years has become a central investigation of hepatic disease.
Low mortality (0.01-0.17%) and low morbidity of this procedure have meant that liver biopsy has become widely used.
LIVER BIOPSYLiver biopsy for long has been considered as an invaluable tool for diagnosis, prognosis and assessment of response to antiviral therapy.
It helps in quantification of necrosis, inflammation, fibrosis and fatwhich is of utmost importance in studying the progression of chronic liver disease
Newer/ non invasive modalities are competing to replace liver biopsy….none has been completely standardised and optimised to replace the “GOLD STANDARD”
• DIAGNOSIS• PARENCHYMAL LIVER DISEASE• ABNORMAL LIVER FUNCTION TESTS• FEVER OF UNKNOWN ORIGIN• FOCAL OR DIFFUSE ABNORMALITIES ON IMAGING
• PROGNOSISSTAGING OF KNOWN PARENCHYMAL LIVER DISEASE
Grading degree of Inflammation Staging degree of fibrosis Define risk for future decompensation Identify patients at risk for HCC
• MANAGEMENT• DEVELOPING TREATMENT PLANS BASED ON HISTOLOGIC ANALYSIS• Assess response to treatment
LIVER BIOPSY INDICATIONS
USE OF LIVER BIOPSY IN CLINICAL PRACTICEDIAGNOSIS STAGING PROGNOSIS MANAGEMENT
Hepatitis B + + + + + + + +Hepatitis C + + + + + + ++++Hemochromatosis + + + + + + + +Wilsons Disease ++ + + + + + _A1-AT + + + + ++ +AIH +++ + + + + ++ + +PBC ++ + + + + +++ + +PSC ++ + _ +Alcohol ++ +++ ++ +NAFLD/NASH ++ ++ ++ +HCC ++ - - + + + +Other focal lesions ++ ++Infiltrative ++++ ++ + ++DILI ++ - - - -ALF ++ - - - ++POST OLTX ++++ +++ ++ ++++
LIVER BIOPSYGRADING AND STAGING SYSTEM FOR
NECROINFLAMMATORY SCORES AND FIBROSIS Ishak modification for hepatic activity index (HAI) for scoring of necro-inflammatory activity in chronic hepatitis
Scheuer classification for grading and staging of chronic hepatitis
Metavir classification for staging of hepatitis C liver disease
Batts–Ludwig
International Association for Study of liver (IASL)
MEASUREMENT OF LIVER FIBROSISSirius red stains most hepatic collagens, (including types I & III, which are the main types involved in liver fibrosis).
Sirius red staining correlates with chemical hydroxyproline assays for collagen under standardised conditions.
Specific staining of biopsies for collagen with interactive image analysis provides specific, precise (sensitive) numerical information about liver fibrosis.
Smaller biopsy is associated with greater sampling error
Error reduced by increasing sample size and number of biopsies performed
Study found 25 mm biopsy had error rate of 25%
Optimal size 30-40 mm
But only 16% of samples are >20 mm
LIVER BIOPSY ADEQUACY
LIVER BIOPSY IN HIV/ HCV Assessment of liver histology may be particularly beneficial in patients with HIV and HCV
These patients have persistently normal ALT levels and may have significant fibrosis; which may be of prognostic importance
This allows clinicians to determine extent of fibrosis and consequently assess suitability for treatment
• DONOR SELECTION• One of the adverse impacts of the world epidemic of obesity/MS is the limited availability of suitable
donors. • Studies showed that steatosis of 30% (15% in LDLT) are not accepted and carries the danger of early
graft loss. ??? fibrosis• Studies showed that biopsy is the gold standard in assessing donor’s steatosis
• POST TRANSPLANT--- FATE OF EXPLANT• Assessment for Rejection—Acute/ Chronic• PROGRESSION of fibrosis (especially in HCV patients)
There is a poor correlation between serological liver tests and liver histology, and there is no accurate non-invasive method for differentiating HCV from rejection till now
LIVER BIOPSY IN TRANSPLANT SETTING
LIVER BIOPSYCONS
Invasive
Risk of complications 1-5%
• Mortality .01% to 0.1%
Limitations
• Sampling error
• Intra-observer variability
PROSSteatosis assessment and quantification
Fibrosis assessment and architectural distortion
Iron level measurement
Diagnose other pathology• Using special stains• other liver disease (viral hepatitis + NAFLD,
etc)
NON INVASIVE TESTS FOR ASSESING FIBROSIS/ INFLAMMATION/ FAT
• IMAGING TECHNIQUES•USG•CT•MRI/E•Hepatic elastography
•SERUM BIOMARKERS• Indirect•Direct
SERUM MARKERS OF FIBROSIS
IDEAL BIOMARKER
Liver specific
Independent of metabolic alterations
Detect fibrosis regardless of cause
Sensitive enough to distinguish between fibrosis stages
Reflective of dynamic changes
NEWER MODALITIES OF ASESSING LIVER FIBROSIS/ INFLAMMATION
TEST DISADVANTAGES ADVANTAGES
SERUM MARKERSDirect None of these markers are liver specific and are influenced
by metabolismNon invasive
Indirect • Not sensitive enough to distinguish between stages
• Degree of fibrosis does not linearly correlate with biopsy stage
• May be better to evaluate for inflammation (i.e., FibroTest)
• NON SPECIFIC FOR LIVER
• Influence of several extra-hepatic factors
Non Invasive
TEST DISADVANTAGES ADVANTAGES
IMAGING MODALITIES
USG Very low sensitivity and negative predictive value High specificity, Non invasive
TE Poor performance in mild to moderate diseaseCannot be used in Patients with ascitesMorbid obesity (BMI>40)CostCannot distinguish between stage 0-II or III-IV
Non Invasive
MRE Increased exposure time---60 minutes Can be performed in obese patientsHigher diagnostic accuracy
ARFI (Acoustic radiation force imaging) Further studies needed in order to specify role of ARFI elastography for non invasive staging of liver fibrosis
Less time consumingSuccessful in obese patients
IMAGING MODALITIES OF ASESSING LIVER FIBROSIS
FIBROSCANNon-invasive
Able to assess a much larger proportion of the liver
Serial measurements to evaluate fibrosis progression
Poor performance in mild to moderate disease
Cannot be used in• patients with ascites• Morbid obesity (BMI>40)
Cost
Cannot distinguish between stage 0-II or III-IV
The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis.
Degos F et al (the FIBROSTIC study) Journal of Hepatology (December 2010)
AASLD CONSENSUS STATEMENTS• Liver biopsy is currently a fundamentally important tool in the management of patients
with liver disease, important for diagnosis as well as staging of liver disease and its use is recommended until clearly superior methodologies are developed and validated (class IIB, level C)
• Liver biopsy is the 'gold standard' for diagnosis and follow up of fibrosis and implementing specific antiviral therapy.
• Protocol liver biopsy is of utmost importance in the post transplant care of patients. (1A)
• Transient elastography for replacing biopsy in the assessment and diagnosis of fibrosis progression still needs validation through large scale clinical studies. (2C)
• Biopsy is the gold standard for assessing the presence and degree of steatosis in the donor graft. (1C)
Rockey D et al. LIVER BIOPSY. Hepatology 2009