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LIVER BIOPSY APASL, STC 2014

LIVER BIOPSY APASL, STC 2014. ALAAELDIN IBRAHIM (MD) Prof. of Medicine University of Benha , Egypt. Consensus statement: Liver Biopsy . Percutaneous liver biopsy is an invasive but safe procedure (1A)

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LIVER BIOPSY APASL, STC 2014

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  1. LIVER BIOPSYAPASL, STC 2014 ALAAELDIN IBRAHIM (MD) Prof. of Medicine University of Benha, Egypt

  2. Consensus statement: Liver Biopsy • Percutaneous liver biopsy is an invasive but safe procedure (1A) • Transjugular liver biopsies may be performed in patients with coagulopathies or other contraindications to percutaneous liver biopsies (1A) • Indication of liver biopsy should be clearly established (1A). • It should be performed only by experts with minimum training of 50 biopsies under supervision (1A) • Patient should be properly prepared: Premedication and Informed consent (1A). • Image guided liver biopsy is strongly recommended (3)

  3. Consensus statement: Liver Biopsy • Biopsy Needle minimum 16G (3) • Core length preferable >15mm or contain at least 10 portal tracts. A repeat pass should be done, if biopsy length is <1 cm (1A). • If there is coagulopathy or thrombocytopenia < 100000/ or Ascites –TJLB is advised (2a) • If fine needle biopsy is performed a cytologist should be available (3) • Quantitation of fibrosis using image analysis may be a reproducible technique, with little inter-observer variation, and should be considered for investigational studies of liver fibrosis .

  4. Liver Biopsy 2014What is new??

  5. Pro and Cons for Liver Biopsy Pros Cons Invasive Risk of complications 1-5% Mortality .01% to 0.1% Limitations Sampling error Intra-observer variability • Steatosis assessment and quantification • Fibrosis assessment and architectural distortion • Iron level measurement • Diagnose other pathology • Using special stains • other liver disease (viral hepatitis + NAFLD, EtOH, etc)

  6. Is Liver Biopsy a Gold Standard? • Perhaps it depends on why biopsy is being done • Yes, if it is : • To diagnose a disease (excluding viral hepatitis) • To exclude other concomitant disease • To measure iron stores • To quantify steatosis • To get special stains for diagnosis • To stage liver disease if fibrosis is evenly distributed

  7. Is Liver Biopsy a Gold Standard? • No, if it is: • To determine cirrhosis • To evaluate for significant fibrosis • To determine stage if fibrosis is unevenly distributed • To follow longitudinally

  8. Future • Hepatitis C • With new DAA with high SVR rates, perhaps a liver biopsy is not needed? Biopsy is not typically performed in genotype 2 and 3 if patient willing to be treated • If liver biopsy and elastography are not equivalent, then what impact does this have on patient characterization in clinical trials? Clinical trials are using FibroScan in Europe instead of liver biopsy • Non-invasive tests need to be validated as predictors of poor outcomes and not just on correlation to liver biopsy stage • Hepatitis B • Will we still need biopsy to determine disease activity to assess for treatment? May not need biopsy in HIV/HBV who were started on ART with Truvada (treatment based on viral load and not on biopsy)

  9. LB limitations

  10. Liver biopsy adequacy • “Most hepatopathologists are satisfied with a biopsy specimen containing at least six to eight portal tracts”. • Bravo AA et al NEJM 344, 495; 2001. • The correct question is: • What size of biopsy will provide a reliable assessment for the patient’s management 6,8,10,12 ?

  11. Liver biopsy adequacy • Guido M and Rugge M. • SeminLiv Dis 24, 89; 2004. • In most diffuse liver diseases examination of 12-15 complete portal tracts is necessary. • ~20mm of a 1.4mm diameter (17 gauge) needle biopsy. • Progressively longer samples of thinner biopsies are needed.

  12. Size of Liver Biopsy • 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 40 mm • But only 16% of samples are >20 mm Bedossa et al. Hepatology2003;38:1449-1457

  13. Sampling Error • Studies have shown 10-30% of cirrhosis was understaged by percutaneous liver biopsy • Study of biopsy of the left and right lobe of the liver found discrepancy in 50% of the samples • Inaccurate by 1 stage • Underestimation of inflammation Regev et al. Am J Gastroenterol2002; 97:2614-2618

  14. Liver biopsy adequacy • Sample adequacy depends on: • Disease aetiology. • Disease distribution. • Stage of disease. • Diameter of needle biopsy. • In most diffuse liver diseases examination of 12-15 complete portal tracts is necessary. • Inadequate samples will give misleading results: • Inadequate small samples tend to underestimate the degree of disease grade and stage.

  15. Inadequate samples give variable resultsSiddique et al. Scand J Gastro 38,427;2003 • 29 pairs of HCV liver biopsies with 4-5 portal tracts in each. • 2 separate R lobe samples, via the same puncture site. • Knodell scoring: ≥2 point difference in: • 20 cases (69%) total necroinflammatory score. • 6 cases (21%) fibrosis score.

  16. Adequate samples give reproducible resultsPersico et al. Am J Gastro 97,491;2002 52 consecutive patients with HCV, paired liver biopsies. Separate, synchronous (18G needle) samples of R and L lobes of liver. Sample mean length R lobe = 2.8+/-1.1cm; L lobe = 2.5+/-0.9 cm. (samples <15mm in 2 patients who were excluded from the analysis) Ishak scoring system: no significant difference in stage or grade between R and L lobe samples.

  17. Consensus Statement • With careful selection of patients, and performance of the procedure appropriately, the complications become exceptionally rare in current clinical practice. Furthermore, the limitations of sampling error and inter-/ intra-observer variability may be avoided by obtaining adequate tissue specimen and having it reviewed by an experienced liver pathologist (1A). • Current noninvasive tools are unqualified to replace LB in clinical practice in the face of specific limitations for each tool, compounded by a poorer performance towards the assessment of the degree of liver fibrosis, particularly for intermediate stages (1A).

  18. Limitations of liver biopsyin NASH

  19. Sampling error • Only 1/50000 of the whole liver tissue is sampled during a liver biopsy, for which sampling error is of concern. • To prevent sampling errors, it is essential to collect a sufficient amount of tissue; the use of a thick needle[21] and collection of 2 or more samples with a sufficient length are recommended

  20. Sampling error • . Making an accurate diagnosis of NASH is dependent on the length of the specimens[22], with a necessary length of 15-16 mm or longer to accurately evaluate fibrosis[23].

  21. Sampling Error • Ratziu et al[24] excised and compared two percutaneous liver biopsy samples from each of 51 NAFLD patients and observed that the consistency in fatty change was relatively high (78%), but the fibrosis stage was different between the two samples in 41% of the patients. • In 35% of the cases with bridging fibrosis observed in one sample, only mild or no fibrosis was noted in the other sample..

  22. Sampling Error • The inconsistency in ballooning degeneration of hepatocytes, an essential feature for the diagnosis of NASH, was 18%, suggesting that NASH may be overlooked when only one sample is collected

  23. Sampling error • In other reports, the results differed by one or more stages between specimens biopsied from the left and right lobes in 30% of the patients[25], and the inflammatory findings were more inconsistent than those of fatty change and fibrosis between biopsied specimens from the left and right lobes[26].

  24. Sampling error • The assessment criteria for the pathological diagnosis recently proposed by the AASLD specify that the right lobe should be biopsied first, and when the left lobe is biopsied before treatment, a sample should also be biopsied from the left lobe after treatment to judge the therapeutic effect[27].

  25. Inter- and intra-observer variability: • Inter- and intra-observer variability also presents a serious problem for the pathological diagnosis of NAFLD. • Younossiet al[28] reported that the evaluations of fatty change (κ = 0.64) and fibrosis (κ = 0.60) were highly consistent among observers, but that the evaluation of inflammatory activity was inconsistent at a high rate (κ =0.33).

  26. Inter- and intra-observer variability • It has also been shown that inter-observer variability remained even when training in histopathological observation was provided in an effort to reduce these inconsistencies[29]. In that study, the post-intervention κ value (0.39) was not significantly different from the pre-intervention κ value (0.27). Measures to solve this problem are needed.

  27. Risk and complications • Regarding the complications of liver biopsy, the incidence of pain is reportedly 20%, but it increases to 84% when a mildly unpleasant feeling is included in the assessment. • The incidence of serious complications and mortality has been reported to be 0.3%-0.57% and 0.01%, respectively[30-32].

  28. Risk and complications • To decrease complications, operators that are trained by an instructor with sufficient experience should perform biopsies, and operation with a US guide and the use of an aspiration-type biopsy needle are recommended[33,34].

  29. References • 21. Goldstein NS, Hastah F, Galan MV, Gordon SC. Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus needle core biopsy specimens. Am J ClinPathol. 2005;123:382–387. [PubMed] • 22. Vuppalanchi R, Unalp A, Van Natta ML, Cummings OW, Sandrasegaran KE, Hameed T, Tonascia J, Chalasani N. Effects of liver biopsy sample length and number of readings on sampling variability in nonalcoholic Fatty liver disease. ClinGastroenterolHepatol. 2009;7:481–486. [PMC free article] [PubMed] • 23. Larson SP, Bowers SP, Palekar NA, Ward JA, Pulcini JP, Harrison SA. Histopathologic variability between the right and left lobes of the liver in morbidly obese patients undergoing Roux-en-Y bypass. ClinGastroenterolHepatol. 2007;5:1329–1332. [PubMed] • 24. Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–1906. [PubMed] • 25. Janiec DJ, Jacobson ER, Freeth A, Spaulding L, Blaszyk H. Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies. Obes Surg. 2005;15:497–501. [PubMed] • 26. Merriman RB, Ferrell LD, Patti MG, Weston SR, Pabst MS, Aouizerat BE, Bass NM. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology. 2006;44:874–880. [PubMed] • 27. Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011;54:344–353. [PMC free article] [PubMed] • 28. Younossi ZM, Gramlich T, Liu YC, Matteoni C, Petrelli M, Goldblum J, Rybicki L, McCullough AJ. Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod Pathol. 1998;11:560–565. [PubMed] • 29. Gawrieh S, Knoedler DM, Saeian K, Wallace JR, Komorowski RA. Effects of interventions on intra- and interobserver agreement on interpretation of nonalcoholic fatty liver disease histology. Ann DiagnPathol. 2011;15:19–24. [PubMed] • 30. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500. [PubMed] • 31. van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU. Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital. Intern Med J. 2006;36:692–699. [PubMed] • 32. Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF) Hepatology. 2000;32:477–481. [PubMed] • 33. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology. 2009;49:1017–1044. [PubMed] • 34. Friedman LS. Controversies in liver biopsy: who, where, when, how, why? CurrGastroenterol Rep. 2004;6:30–36. [PubMed]

  30. References for NASH • 35. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–1419. • 36. Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, Younossi ZM. Long-term follow-up of patients with nonalcoholic fatty liver. ClinGastroenterolHepatol. 2009;7:234–238. • 37. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321. • 38. Hjelkrem M, Stauch C, Shaw J, Harrison SA. Validation of the non-alcoholic fatty liver disease activity score. Aliment PharmacolTher. 2011;34:214–218. • 39. Juluri R, Vuppalanchi R, Olson J, Unalp A, Van Natta ML, Cummings OW, Tonascia J, Chalasani N. Generalizability of the nonalcoholic steatohepatitis Clinical Research Network histologic scoring system for nonalcoholic fatty liver disease. J ClinGastroenterol. 2011;45:55–58. • 40. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53:810–820. • 41. Younossi ZM, Stepanova M, Rafiq N, Makhlouf H, Younoszai Z, Agrawal R, Goodman Z. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology. 2011;53:1874–1882. • 57. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–2474

  31. Physicians' practices for diagnosing liver fibrosis in chronic liver diseases: a nationwide, Canadian survey • Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. • For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians' characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital.Physicians' main concerns regarding noninvasive fibrosis assessment methods were access⁄availability (42.3%), lack of guidelines for clinical use (26.9%) and cost⁄lack of reimbursement (14.4%) • Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. • Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better reimbursement policy to implement noninvasive tools to assess liver fibrosis. Can J GastroenterolHepatol. 2014 Jan;28(1):23-30. SebastianiG, Ghali P, Wong P, Klein MB, Deschenes M, Myers RP

  32. Complications in Liver Biopsy

  33. Complications • HALT-C reported complications of liver biopsy in HCV patients with advanced liver disease • 1.1 % serious adverse events • 0.6% due to bleeding (most common) • More common if platelet <60,000 • INR>1.3 Seeff et al. ClinGastroentrolHepatol 2010; 8:877--83.

  34. Variables important in determining the overall risk of complications • Patient cooperation • Coagulation status • Operator experience • Use of Image guidance • Type of technique • Number of needle passes • Needle diameter • Type of Needle

  35. Pain • Pain is the most common complication of percutaneous liver biopsy, occurring in up to 84% of patients including those with relatively mild discomfort. 102

  36. Pain • When present, pain can usually be managed with small amounts of narcotics, typically codeine. • Moderate to severe pain is seen in only a small proportion of patients and should raise the possibility of a complication such as bleeding or gall bladder puncture.164

  37. Pain • The mechanism of pain following percutaneous biopsy is most likely a result of bleeding or perhaps bile extravasation from the liver puncture wound, with subsequent capsular swelling, although the exact mechanism for this pain remains uncertain.101

  38. Rate of Bleeding • Based on laparoscopic observations, some degree of bleeding occurs after all percutaneous liver biopsies. • Intrahepatic and perihepatic bleeding is also detectable by ultrasonography in 18%-20% of patients after percutaneous biopsy.120,172

  39. Severe Bleeding • Severe bleeding is defined clinically (heralded by : - change in vital signs with radiographic evidence of intraperitonealbleeding -and requires hospitalization, the likelihood of transfusion, or even radiological intervention or surgery. • Such bleeding has been estimated to occur in between 1 in 2500 to 1 in 10,000 biopsies after an intercostal percutaneous approach for diffuse, nonfocal, liver disease. 103,120,124,132,164-169

  40. Severe Bleeding • Severe bleeding is usually clinically evident within 2-4 hours, but late hemorrhage can occur even up to one week after biopsy.171

  41. Moderate Bleeding • Less severe bleeding, defined as: that sufficient to cause pain or reduced blood pressure or tachycardia, but not requiring transfusion or intervention, occurs in approximately 1 in 500 biopsies. • 103,120,124,132,164,165,167-170

  42. Factors Related to Risk of Bleeding • Other factors that are variably reported to be related to the risk of bleeding include: - Operator experience,169,173-175 – - Needle diameter, 176 - The number of passes taken. 103,132 - The type of needle: Whether cutting needles (for example Trucut and automated variants) have a different risk than aspiration needles (i.e., Menghini or Jamshidi) is unknown, although some retrospective data suggests that cutting needles may be associated with slightly greater risk.165,177

  43. Prophylactic blood products to Prevent Bleeding • Whether the use of prophylactic blood products alters the risk of bleeding is currently unknown. • Methods to limit bleeding, such as tract plugging, are attractive because of a theoretically improved ability to prevent bleeding, but definitive data on this point are lacking.

  44. Disorders Associated with Bleeding Risk • Certain types of patients may be at greater risk of bleeding, such as: - Chronic renal failure or those with -Underlying coagulopathy due to congenital abnormalities in coagulation parameters (such as hemophilia) -Cirrhotics who may have acquired abnormalities in coagulation parameters .

  45. PCLB in CRF and DDAVP • Use of DDAVP immediately before liver biopsy (0.3g/kg body weight) in patients with renal failure undergoing invasive procedures has received considerable attention;181-183 • However, whether the risk of bleeding in patients with chronic renal failure is significantly increased or whether use of DDAVP reduces any risk has not been proven. • In patients on chronic renal replacement therapy, dialysis is often performed prior to liver biopsy. • The relative safety of percutaneous biopsy without use of DDAVP in patients with end-stage renal disease who were on dialysis was recently reported.143

  46. LB in Haemophiliacs Liver biopsy can be safely performed in patients with hemophilia and other congenital bleeding disorders, provided correction of the bleeding diathesis is undertaken prior to the biopsy. • 145,157- • 159,178,184

  47. Mortality • Mortality after liver biopsy is usually related to hemorrhage. • It is very uncommon after percutaneous biopsy, but precise figures vary widely in the literature • 103,120,124,132,164,165,167,169 • Death due to bleeding may also be greater after biopsy of malignant lesionsthan in patients with diffuse parenchymal disease.168 • The most commonly quoted mortality rate is less than or equal to 1 in 10,000 liver biopsies. • Mortality after transvenousbiopsy was 0.09% in a recent report of 7649 transvenousbiopsies but, again, may reflect the selection of higher risk patients for this intervention.180

  48. Miscellaneous • pneumothorax, hemothorax, perforation of any of several viscous organs, bile peritonitis, infection (bacteremia, abscess, sepsis), hemobilia, neuralgia, and rare complications such as ventricular arrhythmia with transvenous biopsy.180 • Infectious complications appear to be increased in post-transplant patients who underwent choledochojejunostomy at liver transplantation.185 • Pneumothorax is critical to recognize immediately after biopsy because it can lead to immediate catastrophic outcomes if not promptly recognized and treated.

  49. Recommendations • Those performing liver biopsy must be cognizant of multiple potential complications (including death) that may occur after liver biopsy and discuss these appropriately with their patients beforehand (Class I, Level C). • . Platelet transfusion should be considered when levels are less than 50,000-60,000/mL (this applies whether one is attempting biopsy transcutaneouslyor transvenously) (Class I, Level C). • . The use of prophylactic or rescue strategies such as plasma, fibrinolysis inhibitors, or recombinant factors should be considered in specific situations, although their effectiveness remains to be established (Class IIa, Level C).

  50. Recommendation • In patients with renal failure or on hemodialysis, desmopressin(DDAVP) may be considered, although although its use appears to be unnecessary in patients on stable dialysis regimens (Class IIa, Level B). • Patients on chronic hemodialysis should be well dialyzed prior to liver biopsy, and heparin should be avoided if at all possible (Class I, Level C).

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