LIVER BIOPSY gold standard?...invasive vs non invasive....

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

LIVER BIOPSY PREFERRED INVESTIGATION FOR DIAGNOSIS OF INFLAMMATION AND STAGE OF FIBROSIS IN CHRONIC LIVER DISEASE:

LIVER BIOPSY PREFERRED INVESTIGATION FOR DIAGNOSIS OF INFLAMMATION AND STAGE OF FIBROSIS IN CHRONIC LIVER DISEASE MEHNAAZ SULTAN KHUROO CONSULTANT PATHOLOGIST GOVERNMENT MEDICAL COLLEGE SRINAGAR, J&K

GLOBAL IMPACT OF LIVER DISEASE:

GLOBAL IMPACT OF LIVER DISEASE Liver disease is a major cause of illness and death worldwide Chronic 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 :

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 BIOPSY:

LIVER BIOPSY Liver 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 fat which 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”

Slide5:

DIAGNOSIS PARENCHYMAL LIVER DISEASE ABNORMAL LIVER FUNCTION TESTS FEVER OF UNKNOWN ORIGIN FOCAL OR DIFFUSE ABNORMALITIES ON IMAGING PROGNOSIS STAGING 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 PRACTICE:

USE OF LIVER BIOPSY IN CLINICAL PRACTICE DIAGNOSIS 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 BIOPSY GRADING AND STAGING SYSTEM FOR NECROINFLAMMATORY SCORES AND FIBROSIS :

LIVER BIOPSY GRADING 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 fibrosis:

Measurement of liver fibrosis Sirius 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.

LIVER BIOPSY ADEQUACY :

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 :

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

LIVER BIOPSY IN TRANSPLANT SETTING :

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 Biopsy:

Liver Biopsy CONS Invasive Risk of complications 1-5% Mortality .01% to 0.1% Limitations Sampling error Intra-observer variability PROS Steatosis 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:

NON INVASIVE TESTS FOR ASSESING FIBROSIS/ INFLAMMATION/ FAT IMAGING TECHNIQUES USG CT MRI/E Hepatic elastography SERUM BIOMARKERS Indirect Direct

Serum Markers of Fibrosis:

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:

NEWER MODALITIES OF ASESSING LIVER FIBROSIS/ INFLAMMATION TEST DISADVANTAGES ADVANTAGES SERUM MARKERS Direct None of these markers are liver specific and are influenced by metabolism Non 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

Imaging MODALITIES OF ASESSING LIVER FIBROSIS:

TEST DISADVANTAGES ADVANTAGES IMAGING MODALITIES USG Very low sensitivity and negative predictive value High specificity, Non invasive TE 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 Non Invasive MRE Increased exposure time---60 minutes Can be performed in obese patients Higher 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 consuming Successful in obese patients Imaging MODALITIES OF ASESSING LIVER FIBROSIS

FIBROSCAN:

FIBROSCAN Non-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 p atients 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:

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

Direct Markers:

Direct Markers Measure qualitative and quantitative changes in extracellular matrix markers Markers matrix deposition Procollagen type I carboxy -terminal peptide Procollagen type III amino-terminal peptide Tissue inhibitor of metalloproteinase Transforming growth factor-beta Collagen type IV Markers of matrix removal Procollagen Type IV C peptide Procollagen Type IV N peptide Matrix metalloproteinase Other markers Hyaluronic acid YkL-40 Combination biomarker assay FibroSpect ELF SHASTA None of these markers are liver specific and are influenced by metabolism Afdhal and Shiffman 2006 www.CCO hepatitis.

LIVER BIOPSY IN HEPATITIS B :

LIVER BIOPSY IN HEPATITIS B I nitial trials used pre-treatment and post-treatment biopsy to assess response to nucleoside therapy Knodell index grades histological activity from 0-22 Peri-portal bridging necrosis (0-10) Focal necrosis (0-4) Portal inflammation (0-4) Fibrosis (0-4) Treatment response based on 2 point decrease in necro -inflammatory activity composed of the first three parameters measured (0-18) Lai et al. New Engl J Med 1998;339:61-8

LIVER BIOPSY IN HEPATITIS C :

Clinical trials have used viral response as primary endpoint Liver biopsies pre- and post- treatment done for Confirmation of chronic hepatitis, r/o other causes, identify cirrhosis (staging) reduction in the rate of progression of liver fibrosis. Change in histological activity Knodell HAI METAVIR McHutchison et al. New Engl J Med 1998;339:1485-92 Poynard et al. Lancet 1998;352:1426-32 LIVER BIOPSY IN HEPATITIS C

SVR FOR ASSESSMENT OF RESPONSE TO TREATMENT :

SVR FOR ASSESSMENT OF RESPONSE TO TREATMENT Epidemiological factors including patient age, gender, and race Viral factors, most importantly the pre-treatment viral load, rapid virologic response, and the genotype, and Histological factors including the amount of fibrosis and steatosis Kamal SM, Nasser IA. Hepatology . 2008 Apr; 47(4):1371-83

authorStream Live Help