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Liver biopsy

Liver biopsy..A complete guideline including AASLD SUMMARY points.

Liver biopsy

  1. 1. Pratap Sagar Tiwari, MD, Internal Medicine DM Resident, Hepatology NAMS, Bir Hospital, Nepal
  2. 2. BACKGROUND • The first liver biopsy obtained by aspiration was performed by Paul Ehrlich in 1883 to assess hepatic glycogen content in a diabetic pt, and 12 years later by Lucatello to analyze a tropical abscess of the liver. • Its first application for the diagnosis of liver cirrhosis in humans and rats was published in a series by Schüpfer in France in 1907, and the diagnostic potential was expanded by Bingel in Germany in 1923. • Over the next 50 years the technique of obtaining liver biopsy samples was further developed in regard to approach, needle type and the combination with diagnostic imaging techniques. • Since the publication of a “one second needle biopsy of the liver” by Menghini in 1958, the technique of liver needle biopsy has seen a broad introduction into clinical medicine. • Transvenous liver biopsy was introduced in 1967 as an alternative to percutaneous biopsy in pts with coagulopathy in order to decrease the risk of bleeding.
  3. 3. Indications for liver biopsy Adapted from: Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344:495.
  4. 4. • It is an important tool in the management of liver disease and has three major roles: (i) diagnosis of liver disease that cannot be diagnosed by blood tests or imaging; (ii) assessment of prognosis and staging of liver fibrosis (ii) to assist in making therapeutic decisions.
  5. 5. 1.Roles of liver biopsy: Diagnosis • Although sensitive and accurate blood tests are available for the diagnosis of many liver diseases and the determination of liver fibrosis, and radiological imaging test can diagnose and classify many focal liver lesions, liver biopsy still remains an important diagnostic test for determining the cause of parenchymal liver disease or determining the nature of a liver tumor that does not have typical radiological criteria on imaging.
  6. 6. 1.Roles of liver biopsy: Diagnosis • Liver biopsy also continues to play a role in diseases for which there are no reliable serological markers or in which histological assessment is needed for confirmation. • Liver biopsy is sometimes the only way to make a DX of granulomatous diseases of the liver and may be needed to confirm the DX of WD, a1AT, glycogen storage disease, tyrosinemia, and amyloidosis. • In a study by Skelly et al., liver histology was evaluated in 354 pts in whom serological and radiological evaluation had failed to determine an etiology of liver disease. Over two thirds of the pts were found to have NAFLD, 26% had fibrosis, and 6% had previously unrecognized cirrhosis. • Other conditions diagnosed on biopsy included DILI, cholestatic liver disease, ALD, PSC, AIH, amyloid, glycogen storage disease, and HH.
  7. 7. 1.Roles of liver biopsy: Diagnosis • Liver biopsy is required to reliably differentiate simple steatosis of NAFLD from NASH • To determine the presence of coexisting disease such as overlap syndromes between AIH and PBC. • The use of liver biopsy for the evaluation of a focal liver mass lesion is complex. Many focal mass lesions can be defined by the typical features in CECT with a high degree of accuracy and thus LB is not required. In addition, there are now specific imaging criteria for the diagnosis and classification of HCC put out by the American College of Radiology Imaging Network and adopted by the Organ Procurement and Transplant Network that accurately diagnose and classify HCC lesions. These criteria negate the need for diagnostic biopsy of a suspected HCC.
  8. 8. 2.Prognosis • Liver biopsy has been an important tool for assessing disease severity, fibrosis stage, and prognosis. • However its role here in this arena is rapidly being replaced by noninvasive biomarkers of liver fibrosis and imaging studies such as transient elastography.
  9. 9. 3.Treatment • Liver biopsy has played an important role in determining the need for RX of many liver conditions. • In the interferon era of HCV treatment, the decision to treat the HCV largely depended on the presence of liver fibrosis. • With the advent of highly effective DAAs for the RX of HCV, fibrosis assessment is less important in treatment decisions . • In the setting of AIH, the histological pattern of the liver injury is included in the scoring system of the International Autoimmune Hepatitis Group and is also part of the determination to institute treatment of AIH. • Liver biopsy prior to termination of RX is also the only method by which to ensure full resolution of the disease and an optimal endpoint of therapy, as interface hepatitis is found in 55% of pts with normal AST and γ-globulin levels during therapy and these individuals typically relapse after cessation of RX.
  10. 10. 3.Treatment • Liver biopsy plays a critical role in the management of the transplanted liver allograft in determining the etiology of elevated LFTs and assessing response to therapy. • Some LT programs perform annual protocol liver biopsies for monitoring the allograft although there is not much compelling evidence for this in the absence of underlying disease.
  11. 11. Types of liver biopsy • PERCUTANEOUS LIVER BIOPSY Transthoracic (transpleural or transparietal) Subcostal liver biopsy Plugged liver biopsy • TRANSVENOUS (TRANSJUGULAR) LIVER BX • LAPAROSCOPIC LIVER BIOPSY • Endoscopic US-guided transgastric liver biopsy Percutaneous liver biopsy may be classified according to the site of entry of the biopsy needle, whether the biopsy is performed in a blind or guided manner, or whether the biopsy track is plugged after the procedure. If the patient has an enlarged liver extending below the costal margin, then the site of entry of the biopsy needle may be subcostal. Complications are slightly more frequent with the transthoracic (4.1%) than the subcostal route (2.7%).[1] Perrault, J, McGill, DB, Ott, BJ, and Taylor, WF. Liver biopsy complications in 1000 inpatients and outpatients. Gastroenterology. 1978; 74: 103–106 Plugged liver biopsy Plugged liver biopsy is a modification of the percutaneous approach . It has been advocated as an alternative method for obtaining liver tissue in patients with impaired coagulation where transjugular biopsy is not available. In this technique a biopsy samples is taken using a Tru-cut needle in the conventional manner but only the obturator containing the specimen is removed leaving the outer cutting sheath within the liver substance. A plastic cannula is then inserted down the sheath and while the breath is still held in expiration, gelatin or gel foam is injected as the sheath is withdrawn.
  12. 12. Blind and guided liver biopsies • A blind liver biopsy is one which is done without imaging of the liver immediately prior to taking the biopsy sample. • A guided biopsy can be defined as a liver biopsy that is undertaken during real time imaging of the liver, whether that imaging modality be ultrasound, CT or MRI. • Thus, guided biopsies should give access to thicker hepatic parenchyma, should avoid the puncture of adjacent organs, and should allow the accurate biopsy of focal hepatic lesions where appropriate.
  13. 13. Percutaneous liver biopsy • PLB is a procedure in which a long needle is introduced through the skin, subcutaneous tissues, intercostal muscles, and peritoneum into the liver to obtain a specimen of liver tissue. [1,2] • This procedure is usually performed on an outpatient basis. The pt is then observed for a few hours in the hospital or the ambulatory unit. • It is safe in pediatric [3,4] as well as adult pts, with a low complication rate. 1. Karamshi M. Performing a percutaneous liver biopsy in parenchymal liver diseases. Br J Nurs. 2008 Jun 26-Jul 9. 17(12):746-52. 2. Myers RP, Fong A, Shaheen AA. Utilization rates, complications and costs of percutaneous liver biopsy: a population-based study including 4275 biopsies. Liver Int. 2008 May. 28(5):705-12. 3. Almeida P, Schreiber RA, Liang J, Mujawar Q, Guttman OR. Clinical Characteristics and Complications of Pediatric Liver Biopsy: A Single Centre Experience. Ann Hepatol. 2017 Sep-Oct. 16 (5):797-801. 4. Bolia R, Matta J, Malik R, Hardikar W. Outpatient Liver Biopsy in Children: Safety, Feasibility, and Economic Impact. J Pediatr Gastroenterol Nutr. 2017 Jul. 65 (1):86-88.
  14. 14. Requirement needed to perform outpatient LBX Outpatient liver biopsy can be performed if: 1. the patient can easily return to a hospital 2. the patent has a reliable individual to stay with during the first post- biopsy night 3. the patient has no serious conditions that would increase the risk of the biopsy (e.g., ascites, encephalopathy, coagulopathy, heart failure or advanced age) 4. there is access to blood transfusion, inpt admission and sufficient staff for post-biopsy observation • The patient should be hospitalized if there are postprocedure complications, including bleeding, bile leak, pneumothorax or other organ puncture. Schiff
  15. 15. Contraindications to Percutaneous Liver biopsy Absolute • Uncooperative patient [1] • PT>4 seconds over control, INR >1.5 [2] • Platelet count <60 000/mm3 • Unavailability of blood transfusion support • Serious consideration of echinococcal cyst • Serious consideration of hemangioma of other vasculars • Bleeding diathesis (eg, hemophilia) • Bowel overlying biopsy site (on ultrasonography or other abdominal imaging) • Recent use (within the last 7 days) of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) or antiplatelet class of medications Relative • Ascites • Infection in the right pleural cavity • Abdominal wall infection over the identified biopsy site • Morbid obesity • Amyloidosis • Extrahepatic biliary obstruction , Bacterial Cholangitis 1. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001 Feb 15. 344(7):495-500. 2. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. British Society of Gastroenterology. Gut. 1999 Oct. 45 Suppl 4:IV1-IV11.
  16. 16. THE UNCOOPERATIVE PATIENT • In percutaneous LB it is essential that the pt is cooperative as an untoward movement when the biopsy needle is in the hepatic parenchyma can lead to a tear of the liver and capsule and subsequent torrential bleeding. • If the pt is frightened, then the use of midazolam as sedation can be considered with no increased risk. [1] • If the pt remains uncooperative and the benefit of obtaining liver histology outweighs the risk to the patient, then LB under general anaesthesia should be considered. 1. Alexander JA, Smith BJ.Midazolam sedation for percutaneous liver biopsy. Dig Dis Sci 1993;38:2209–11.
  17. 17. EXTRAHEPATIC BILIARY OBSTRUCTION • Extrahepatic biliary obstruction is frequently quoted as a contraindication to LB which may be complicated by pain, biliary peritonitis, septicaemic shock, and death.[1] • However, in one study, serious complications in at least 2% of pts (including biliary peritonitis) and significant complications in another 4% followed the percutaneous LB.[2] • With current imaging techniques (specifically ERCP and MRI cholangiography), liver biopsies should only be performed in the context of biliary obstruction when there is doubt about the diagnosis and the benefit to the pt outweighs the risk. Under these circumstances the transjugular approach would be preferable.[3] 1. LoIudice T, Buhac I, Balint J. Septicaemia as a complication of percutaneous liver biopsy. Gastroenterology 1977;72:949–51. 2. Morris JS, Gallo GA, Scheuer PJ, et al. Percutaneous liver biopsy in patients with large bile duct obstruction. Gastroenterology 1975;68:750–4. 3. Rosch J, Lakin PC, Antonovic R, et al. Transjugular approach to liver biopsy and transhepatic cholangiography. N Engl J Med 1973;289:227–31.
  18. 18. BACTERIAL CHOLANGITIS • The risk of inducing peritonitis and septic shock after LB has made cholangitis a relative contraindication. • However, if a liver biopsy is performed when the biliary system is infected, then culture of a piece of liver can give useful bacteriological information especially in the context of investigation of TB or a PUO. • Bacteraemia after percutaneous biopsy of a normal liver is a well recognised phenomenon[1] and occurs in up to 14% of biopsies.[2] • These findings confirm the risks of disseminating infection at the time of liver biopsy. 1. McCloskey RV, Gold M, Weser E. Bacteraemia after liver biopsy. Arch Intern Med 1973;132:213–15. 2. Le Frock JL, Ellis CA, Turchik JB, et al. Transient bacteraemia associated with percutaneous liver biopsy. J Infect Dis 1975;131:S104–7.
  19. 19. ABNORMAL COAGULATION INDEXES • There are widely divergent opinions about the values at which abnormal coagulation indexes become CI to percutaneous LB. • A number of investigators have shown that the degree of bleeding from the liver puncture site (observed at laparoscopy) bears no correlation to peripheral blood coagulation parameters, mentioned later, when these parameters are modestly increased.[1,2] • Some of these investigators have postulated that this discrepancy in liver bleeding time may be due to the inherent elasticity of the biopsy track collapsing down after the core has been taken, together with the high local concentrations of clotting factors within the hepatic parenchyma.[3] • It should, however, be borne in mind that during a blind percutaneous LB, the liver is not the only structure to be punctured and the skin and subcutaneous tissues (and occasionally other organs) can bleed. Thus, peripheral indexes of clotting must still be taken into consideration. • In the absence of factor concentrate inhibitors, LB is safe if the clotting abnormalities are corrected before and for 24 hours after biopsy.[4,5] 1. Dillon JF, Simpson KJ, Hayes PC. Liver biopsy bleeding time—an unpredictable event. J Gastroenterol Hepatol 1994;9:269–71. 2. Gazelle GS, Haaga JR, Rowland D. Effect of needle gauge, level of anticoagulation, and target organ on bleeding associated with aspiration biopsy. Radiology 1992;183:509–13. 3. Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981;26:388–93. 4. Wong VS, Baglin T, Beacham E, et al. The role for liver biopsy in haemophiliacs infected with the hepatitis C virus. Br J Haematol 1997;97:343–7. 5. Ahmed MM, Mutimer DJ, Elias E, et al. A combined management protocol for patients with coagulation disorders infected with hepatitis C virus. Br J Haematol 1996;95:383–8.
  20. 20. Prothrombin time • Several large studies have failed to show an increased risk of bleeding a/with a prolongation of the PT of 4 secs above control values.[1,2,3] • The largest retrospective study of percutaneous LB to date failed to show any correlation between a prolongation of PT by 7 secs over control values and the occurrence of haemorrhagic complications.[4] • By contrast, a number of other studies, however, have corroborated the widely held belief that a coagulopathy predisposes the pt to haemorrhage after percutaneous LB.[5] • The 1991 BSG audit of the biopsy practice in 189 health districts in the UK showed that bleeding was commoner if the INR was raised, with 3.3% of the bleeds occurring when INR was between 1.3-1.5, and 7.1% occurring when the INR >1.5. [6] • This suggests that about 90% of the bleeds occurred in pts with an INR<1.3 and reinforces the fact that having a normal INR or PT is no reassurance that the patient will not bleed after the procedure. 1. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400. 2. Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981;26:388–93. 3. Dillon JF, Simpson KJ, Hayes PC. Liver biopsy bleeding time—an unpredictable event. J Gastroenterol Hepatol 1994;9:269–71. 4. Piccininio F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. J Hepatol 1986;2:165–73. 5. Mahal AS, Knauer CM, Gregory PB. Bleeding after liver biopsy: how often and why? Gastroenterology 1979;76:1192. 6. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41.
  21. 21. Thrombocytopaenia • The level at which thrombocytopaenia becomes a CI to percutaneous LB is uncertain from published data. • Menghini et al: proposes a platelet count>100 000/mm3 [1] • The Mayo Clinic regard counts as low as 56 000/mm3 to be safe.[2] • Most recognised UK texts : platelet count >80 000/mm3 [3] • A survey of mostly US centres : platelet counts >50 000/mm3.[4] • One study of 87 pts found that those pts with a platelet count <60000/mm3 were significantly more likely to bleed after percutaneous LB than those with platelet counts above this value.[5] • The evidence for a cut off value remains scanty and takes no account of the function of the platelets. 1. Menghini G, Antonini R, Bruschelli P. Open abdomen liver biopsy by a modified one-second technic. Am J Surg 1977; 133:383–4. 2. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400. 3. Sherlock S, Dooley J. Diseases of the liver and biliary system. 10th edn. London: Blackwell Scientific, 1997. 4. Sue M, Caldwell SH, Dickson RC, et al. Variation between centres in technique and guidelines for liver biopsy. Liver 1996;16:267–70. 5. Sharma P, McDonald GB, Banaji M. The risk of bleeding after percutaneous liver biopsy: relation to platelet count. J Clin Gastroenterol 1982;4:451–3.
  22. 22. Thrombocytopaenia • The effect on bleeding of thrombocytopaenia due to hypersplenism compared with thrombocytopaenia resulting from bone marrow failure has, not been studied in detail. • The absolute value of the platelet count may not be crucial in determining the risk of bleeding as it is well recognised that even those pnts with normal prothrombin times and platelet counts can have severely deranged bleeding times. • Nevertheless, for a percutaneous liver biopsy the minimum platelet count felt to be safe without the need for support is 60 000/mm3.
  23. 23. Complication Rate of Percutaneous Liver Biopsies among Persons with Advanced Chronic Liver Disease in the HALT-C Trial • Background & Aims—It is not known whether persons with advanced CLD have a greater risk of complications from liver biopsy than pts with more mild, CLD. The safety and complications of liver biopsy were examined in pts with hep C-related bridging fibrosis or cirrhosis that were enrolled in the Hep C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial. • Methods—Standard case report forms from 2,740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, along with information from questionnaires completed by investigators about details of LB techniques used at each hospital. • Results—There were 29 serious adverse events (1.1%); the MC was bleeding (16 cases,0.6%). There were no LB-related deaths. Bleeding rate was higher among pts with plt ≤60,000/mm3 and among those with an INR ≥1.3, although none of the pts with an INR >1.5 bled. Excluding subjects with a plt≤60,000/mm3 would have reduced the bleeding rate by 25%(4/16), eliminating only 2.8%(77/2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under US guidance did not influence the frequencies of adverse events. • Conclusions—Approximately 0.5% of persons with hepC and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in pts with platelet counts ≤60,000/mm3. Seeff LB. Complication Rate of Percutaneous Liver Biopsies among Persons with Advanced Chronic Liver Disease in the HALT-C Trial. Clin Gastroenterol Hepatol. 2010 October ; 8(10): 877–883. doi:10.1016/j.cgh.2010.03.025.
  24. 24. Platelet function/bleeding time • The practice of measuring bleeding time (BT) before liver biopsy is much more common in Asia compared with the USA (73 v 36%).11 • BT is seldom measured in UK centres prior to liver biopsy even though the ingestion of aspirin and other NSAID in the week prior to invasive intervention is a recognized CI by several authorities. • No convincing data to support this as a contraindication to percutaneous liver biopsy. • Pts with renal impairment usually have abnormalities of platelet function. According to one small study, pts with ESRD on haemodialysis are at high risk (up to 50%) of haemorrhagic complications after percutaneous LB, independent of the BT.46 • This same study suggested that LT recipients with a BT >10 minutes (ULN) had a higher incidence of bleeding complications compared with those with a BT <10 mins. The sample size, however, is too small to allow any firm conclusions to be drawn. 1. Sue M, Caldwell SH, Dickson RC, et al. Variation between centres in technique and guidelines for liver biopsy. Liver 1996;16:267–70. 2. Wolf DC, Weber F, Palascak I, et al. Role of the template bleeding time in predicting bleeding complications of percutaneous liver biopsy [abstract]. Hepatology 1995;22:509A.
  25. 25. ASCITES • Percutaneous LB in the presence of tense ascites is considered a CI in many texts. • The reasons for this vary from the high likelihood of not obtaining a biopsy specimen because of the distance between the abdominal wall and the liver to the risk of uncontrollable bleeding into the ascites. • Although these reasons seem to be sensible, they are not substantiated in RCT. There is evidence, however, to support the fact that CT or US guided LB in the presence of ascites does not affect the complication rate.48 49 • Not withstanding these studies, it seems logical that if a LB is clinically indicated in a pt with tense ascites then there are several alternatives, the most obvious being to perform a total paracentesis prior to performing the percutaneous biopsy. Other options include image guided biopsy, transjugular liver biopsy, or laparoscopic biopsy. 1. Little AF, Ferris JV, Dodd GD, et al. Image guided percutaneous hepatic biopsy: Effect of ascites on the complication rate. Radiology 1996;199:79–83. 2. Murphy FB, Barefield KP, Steinberg HV, et al. CT- or sonography-guided biopsy of the liver in the presence of ascites: frequency of complications. AJR Am J Roentgenol 1988;151:485–6.
  26. 26. CYSTIC LESIONS • Modern imaging techniques can often identify benign cystic lesions of the liver, thereby eliminating the need for biopsy in many cases. • Cystic lesions within the liver may communicate with several structures incl. the biliary tree and therefore pose a risk of biliary peritonitis after LB. • The cystic lesion quoted most often as a CI to percutaneous LB was the echinococcal cyst because of the risk of dissemination of the hydatid cysts throughout the abdomen, and the risk of anaphylaxis. • Recent advances in the treatment of hydatid disease of the liver mean that this may no longer be so.[1] • Aspiration of hydatid cysts with 19–22 gauge needles under US guidance has been shown to be safe and can be used both diagnostically[2] and therapeutically[3] for the injection of hypertonic saline or 95% ethanol under albendazole cover. 1. Kumar A, Chattopadhyay TK. Management of hydatid disease of the liver. Postgrad Med J 1992;68:853–6. 2. Bret PM, Fond A, Bretagnolle M, et al. Percutaneous aspiration and drainage of hydatid cysts in the liver. Radiology 1988;168:617–20. 3. Filice C, Pirola F, Brunetti E, et al. New therapeutic approach for hydatid liver cysts. Gastroenterology 1990;98:1366–8.
  27. 27. AMYLOIDOSIS • The use of LB in the DX of amyloid liver disease was first used in 1928. Volwiler and Jones reported the first death from haemorrhage after amyloid liver biopsy.[1] • This episode together with further reports of haemorrhage after LB in pts with amyloid have lead to the inclusion of amyloid liver disease in the list of CI to percutaneous LB.[1] • No large controlled trials have been performed to date which show an increased risk of haemorrhage after liver biopsy in amyloid liver disease. However, in 1961 a small series of LB in amyloid liver disease was reported. One of 18 pts had an intraperitoneal bleed but this patient was treated conservatively.[2] • Stauffer and colleagues[2] decided that LB was a useful method in the establishment of the diagnosis of hepatic amyloid, and certainly in the context of the investigation of hepatomegaly of uncertain aetiology this seems reasonable. • However, if a diagnosis of amyloidosis had already been made or is strongly suspected, then a specific indication for performing a percutaneous LB is needed rather than for performing a more benign procedure such as a rectal biopsy. 1. VolwilerW, Jones CM. The diagnostic and therapeutic value of liver biopsies; with special reference to trocar biopsy. N Engl J Med 1947;237:651. 2. Stauffer MH, Gross JB, Foulk WT, et al. Amyloidosis: Diagnosis with needle biopsy of the liver in 18 patients. Gastroenterology 1961;41:92–6
  28. 28. The biopsy procedure: INFORMED CONSENT • Informed consent should be obtained in writing prior to the biopsy procedure in accordance with individual hospital policies. • Consent forms should contain the pt’s native language wherever possible, and when this is not possible there should be access to a competent interpreter to ensure adequate understanding by the pt of both the risks and benefits of the procedure and the commands given to them during the biopsy
  29. 29. The biopsy procedure: EXPERIENCE OF THE OPERATOR • There are no good data to show that the grade of the person performing the percutaneous LB has any affect upon the complication rate after the biopsy. • The only data available are that from the 1991 BSG audit showing that the frequency of complications was slightly higher if the operator had performed less than 20 biopsies (frequency of complications was 3.2% if operator had performed <20 biopsies compared with 1.1% if the operator had performed >100 biopsies). No difference in the complication rates between gastroenterologists and general physicians was seen.[1] • It is recommended that pre-registration house officers should not perform percutaneous LB except in the context of specialized units, and then only under close supervision. 1. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41.
  30. 30. The biopsy procedure: SEDATION • Anxious pts should be given the opportunity to have midazolam sedation for the biopsy procedure otherwise only local anaesthesia is enough. • Midazolam should be given with caution in the context of liver disease. REFER TO PREVIOUS SLIDE “THE UNCOOPERATIVE PATIENT”
  31. 31. The biopsy procedure: HAEMATOLOGICAL INVESTIGATIONS • All pts undergoing percutaneous LB should have blood grouped and serum saved, and in hospitals where facilities for cross matching are limited, pts should have blood available. • The PT(or INR) and platelet count should be checked prior to the biopsy (preferably within 24 hours). • If the PT is prolonged by four secs or more (or INR>1.4) then other strategies to improve the coagulopathy should be tried. • The level of the platelet count at which a percutaneous LB should not be done is as controversial; however, there is evidence that in pts with a platelet count as low as 60 000 /mm3, a percutaneous LB can be performed with no increase in complication rate.
  32. 32. Recommendations : BMJ • If the platelet count is > 60 000/mm3 then the biopsy can be safely performed. • If the platelet count is 40 000–60 000/mm3 then platelet transfusion may increase the count enough for the biopsy to be performed safely by the percutaneous route. • If, however, platelet transfusion does not increase or the platelet count is <40000/mm3 then alternative biopsy methods such as plugged, transvenous (transjugular), or laparoscopic liver biopsy can be tried. • If the PT is <4 sec prolonged, then percutaneous biopsy can be safely undertaken. • If the PT is 4–6 sec prolonged then, a transfusion of FFP may bring the PT into the desired range. • If the PT>6 sec prolonged then other biopsy methods should be tried. A Grant, J Neuberger. Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(Suppl IV):IV1–IV11
  33. 33. The biopsy procedure: Vitamin K, FFP & platelet transfusion • Vit K, FFP and platelet support are widely used for the correction of coagulation abnormalities prior to liver biopsy. • Vit K is useful but should be given parenterally and at least 6 hrs before the biopsy, and is most effective where the disturbance in coagulation is caused by biliary obstruction or malabsorption. If this does not work then FFP given immediately prior to the biopsy in a dose of 12–15 ml/kg body wt may correct the PT.[1,2] • Platelet transfusion prior to percutaneous LB,if required: It has been suggested that pts should initially receive 1 unit per 10 kg body wt and the effect of this transfusion be assessed by the platelet count obtained one hour later.[3] • However, posttransfusion platelet increments do not necessarily correlate with decreased risk of bleeding as platelet function may vary and it has been shown that 30% of pts receiving platelet transfusion show no improvement in in vitro BT(a measure of platelet function).[4] 1. Spector MD, Corn M, Ticktin HE. Effect of plasma transfusions on the prothrombin time and clotting factors in liver disease. N Engl J Med 1966;275:1032–7. 2. Contreras M, Ala FA, Greaves M, et al. Guidelines for the use of fresh frozen plasma. Transfus Med 1992;2:57–63. 3. Consensus Conference. Platelet transfusion therapy. JAMA 1987;257:1777–80. 4. Kristensen J, Eriksson L, Olsson K, et al. Functional capacity of transfused platelets estimated by the Thrombostat 4000/2. Eur J Haematol 1993;51:152–5.
  34. 34. Restarting of Antiplatelet/anticoagulants post procedure • There are few data to support when anticoagulant and antiplatelet medications can be restarted after a liver biopsy, but the AASLD guidelines on liver biopsy suggest starting warfarin the day after liver biopsy and antiplatelet agents 48–72 hours after the procedure.
  35. 35. The biopsy procedure: PROPHYLACTIC ANTIBIOTICS • Bacteraemia associated with LB in both structurally normal and abnormal livers has been well documented.[1,2] • Therefore, prophylactic antibiotics should be used in the context of valvular heart disease or when there is previously documented bacteraemia. • The current data on the use of prophylactic antibiotics are inconclusive and we feel that for pts in whom biliary sepsis is suspected it is prudent to use antibiotics. 1. McCloskey RV, Gold M, Weser E. Bacteraemia after liver biopsy. Arch Intern Med 1973;132:213–15. 2. Le Frock JL, Ellis CA, Turchik JB, et al. Transient bacteraemia associated with percutaneous liver biopsy. J Infect Dis 1975;131:S104–7.
  36. 36. The biopsy procedure: NUMBER OF PASSES • It has been demonstrated that taking more than one core of liver at biopsy can increase the diagnostic yield, but this may have an effect on morbidity. • It has been clearly shown that making more passes increases the incidence of complications when the percutaneous biopsy is taken by either transthoracic or subcostal approaches. • In one paper the increased incidence reached significance when more than three biopsy samples were taken.[1] • This was subsequently confirmed by other studies showing that when blind percutaneous LB is undertaken, taking two specimens improves diagnostic yield with an increased number of minor complications when more than three consecutive specimens are taken.[2] 1. Perrault J, McGill DB, Ott BJ, et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978;74:103–6. 2. Maharaj B, Bhoora IG. Complications associated with percutaneous needle biopsy of the liver when one, two, or three specimens are taken. Postgrad Med J 1992;68:964–7.
  37. 37. The biopsy procedure: NUMBER OF PASSES • A large study of 9212 liver biopsies also showed that the risk of haemorrhage does not only increase with the number of passes made, but is also significantly linked to the age of the patient and the presence of malignancy.16 • Therefore we conclude that under circumstances where the likelihood of a sampling error is high, such as in some cases of macronodular cirrhosis, two samples could be taken. • However, the decision to do this for patients with advanced age or malignancy should be tempered by the increased risk of complications. 1. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400.
  38. 38. PRE-BIOPSY ULTRASOUND • Whether all pts about to undergo percutaneous LB should have an US is a contentious issue. • US is a safe and readily available investigation. One of the reasons for performing a pre-biopsy ultrasound is to rule out anatomical variation—for example, Chilaiditi syndrome where bowel lies between the liver and the abdominal wall, thereby avoiding inadvertent puncture of an adjacent viscus. [1] • US also permits the detection of focal lesions (which may or may not have been suspected) allowing for the opportunity of a targeted biopsy or FNA at a later date under image guidance with a lower risk of haemorrhage. • Percussing for the superior and inferior borders of the liver is usually adequate for selection of the biopsy site [2]; however, in some pts where the borders of the liver are unclear (e.g. obese or cirrhotic pts) US is helpful. • Ultrasound can be either used to “mark” the spot for the liver biopsy or used in real time by the operator. 1. Dixon AK, Nunez DJ, Bradley JR, et al. Failure of percutaneous liver biopsy: Anatomical variation. Lancet 1987;ii:437–9. 2. Qureshi WA, DuBose TJ. Effect of operator experience on liver biopsy site selection [abstract]. Gastroenterology 1997; 112:A37.
  39. 39. Types of needles • Needles used to perform percutaneous liver biopsies are divided into 1. Suction needle devices (Menghini, Jamshidi, and Klatskin) 2. Cutting needles (Tru-Cut needles and spring-loaded devices) • Suction biopsy needles have been shown to cause more tissue fragmentation in cases of cirrhosis .
  40. 40. Suction needle devices Menghini Technique Aspiration Needle Set Pic Source: http://www.petsurgical.com/menghini-technique-aspiration-needle-set-tw-16g-x-2-75/ Pic source: https://www.medpluspro.com/bdtm-klatskin-needle.html Klastkin Aspiration Needle Set
  41. 41. Cutting needles Vim Silverman needle Pic source: http://ilovepathology.com/vim-silverman-liver-biopsy-needle/ Pic source: http://mediwikis.com/wiki/index.php/File:Trucut_image_principle.png user: Michael Edwards
  42. 42. Cutting needle: biopsy gun Pic source: http://www.svuhradiology.ie/interventional-radiology/image-guided-biopsy/
  43. 43. Percutaneous liver biopsy (PLB): Procedure • The procedure is performed with the pt lying supine, the right arm extended, and the right hand placed above the head. • Pts are frequently anxious and light conscious sedation can be used in the appropriate monitored setting. • The “classic” PLB is performed via the transthoracic approach at the point of maximal percussion dullness (usually between 6th -9th ICS) on inspiration and expiration between the mid- and anterior-axillary lines. • After anesthetizing with 1% xylocaine, a small incision is made over the determined site. • The liver biopsy needle is advanced through the skin and subcutaneous tissue. The pt is asked to exhale and hold their breath and the liver biopsy needle is introduced into the liver, with suction in the case of a Menghini, Klatskin, or Jamshidi needle and withdrawn. • When using a Tru-Cut needle or spring-loaded needle,( and I prefer biopsy gun) the needle stays in the liver for a longer time period.
  44. 44. POST-BIOPSY OBSERVATION • The decision about the length of time that a pt should remain in hospital after a blind percutaneous LB is dependent on several factors. • The main consideration in practical terms however is the likely time period in which complications are going to occur. It has been shown that delayed haemorrhage can occur up to 15 days after percutaneous LB in pts who develop a postbiopsy coagulopathy.70 • The occurrence of delayed haemorrhage is also documented after the reinstatement of warfarin therapy several days after percutaneous LB. • Clearly, pts cannot be kept in hospital for two weeks or more after LB so a compromise has to be made on the basis of current knowledge. 1. Reichert CM, Wiesenthal LM, Klein HG. Delayed haemorrhage after percutaneous liver biopsy. J Clin Gastroenterol 1983;5:263–6.
  45. 45. POST-BIOPSY OBSERVATION: how long ? • The first large studies addressing the issue of post-biopsy observation were stimulated by the drive to perform outpatient percutaneous liver biopsies. • These papers showed that the majority of complications occurred in the first three hours after liver biopsy,[1,2] and recommended that pts should be kept in hospital for 6 hours after the procedure. But in our context it is advisable to observe for 24 hrs inpatiently. • A later paper described 61% of complications after liver biopsy occurring in the first two hours, 82% of complications occurring in the first 10 hours, and 96% of complications occurring in the first 24 hours. In this paper recounting 68 276 liver biopsies, six patients died, and all showed signs of bleeding within six hours of the procedure.[3] 1. Perrault J, McGill DB, Ott BJ, et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978;74:103–6. 2. Knauer MC. Percutaneous biopsy of the liver as a procedure for outpatients. Gastroenterology 1978;74:101–2. 3. Piccininio F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. J Hepatol 1986;2:165–73.
  46. 46. POST-BIOPSY OBSERVATION: position & vitals monitoring ? • The position that the patient should be nursed in after the liver biopsy has not been investigated, and various centres have differing policies including nursing the patient supine, on their right hand side or simply “flat”.[1,2] • No controlled trials have been performed to assess these different techniques. • Standard percutaneous liver biopsy observations include monitoring the patient’s vital signs every 15 minutes for the first two hours, then every 30 minutes for two hours and then hourly for the rest of the remaining period. 1. Perrault J, McGill DB, Ott BJ, et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978;74:103–6. 2. Douds AC, Joseph AEA, Finlayson C, et al. Is day case liver biopsy underutilised? Gut 1995;37:574–5.
  47. 47. MORTALITY • The reported mortality from percutaneous LB varies considerably. This is partly because most of the larger series reporting LB complications have been retrospective.[1,2] • The overall mortality rate in the 3 months after LB has been reported to be as high as 19%.[3] Most of these deaths are the result of hepatic malignancy and advanced liver failure, and very few are due solely to the liver biopsy. • The overall mortality rate also varies according to the centre in which the LB were performed—for example, in the Mayo Clinic the mortality from fatal haemorrhage after percutaneous biopsy was 0.11%,[4] whereas in an audit of LB performed in United Kingdom district general hospitals the death rate was between 0.13 and 0.33%.[3] • A generally accepted mortality rate in standard textbooks is between 0.1 and 0.01%.[5] 1. Piccininio F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. J Hepatol 1986;2:165–73. 2. Lebrec D, Goldfarb G, Degott C, et al. Transvenous liver biopsy. Gastroenterology 1982;83:338–40. 3. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41. 4. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400. 5. Sherlock S, Dooley J. Diseases of the liver and biliary system. 10th edn. London: Blackwell Scientific, 1997.
  48. 48. Causes of mortality • The main cause of mortality after percutaneous LB is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68 000 percutaneous LB in which all 6 pts who died did so from intraperitoneal haemorrhage.[1] • Three of these pts had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.[2,3] • Other serious complications responded to treatment; puncture of viscera was never followed by serious clinical complications. • Other series have shown, however, that puncture of the GB followed by biliary peritonitis is a recognized cause of death.[4] 1. Piccininio F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. J Hepatol 1986;2:165–73. 2. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400. 3. Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981;26:388–93. 4. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41.
  49. 49. Causes of mortality • As the main source of mortality after percutaneous LB is haemorrhage, it is reasonable to assume that improvements in mortality rates can be made if the clinician understands the risk factors for bleeding, recognises bleeding promptly and aggressively resuscitates the pt. • It has been suggested that pts with suspected biliary peritonitis should have an early laparotomy. • It has also been suggested that pts who bleed significantly (i.e. pts whose haemoglobin falls to >20 g/l or who become haemodynamically unstable) should be considered for either laparotomy or therapeutic angiography if the bleeding does not stop with transfusion alone.[1] 1. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41.
  50. 50. MORBIDITY • Although many groups have studied complications, there is no consensus about the division into major and minor symptoms and whether complications such as asymptomatic post-biopsy intrahepatic haematoma should be included in the figures. • A morbidity rate of 5.9% for pts suffering minor complications after liver biopsy has been reported.[1] • Sixty percent of complications occur within 2 hours and 96% within 24 hours. • Hospitalization is required in 1.4–3.2% of pts who undergo a percutaneous liver biopsy, with pain and hypotension being the most common reasons for admission. 1. Perrault J, McGill DB, Ott BJ, et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978;74:103–6.
  51. 51. MORBIDITY • Pain is probably the commonest complication of LB occurring in up to 30% [1,2] (some authors state upto 84 %) with moderate and severe pain occurring in 3 and 1.5%, respectively.[3] Hypotension and vasovagal episodes are common accompaniments to pain, occurring in about 3% of LB.[3] . • Significant haemorrhage (indicated by a drop in haemoglobin of >20 g/l) occurs in 0.35–0.5% of all procedures.[4,5] • Subclinical bleeding, however, occurs in a much higher percentage of pts, with up to 23% of pts having intrahepatic or subcapsular haematomas detectable by US 24 hours after biopsy.[6] These haematomas are generally small and are not a/with significant haemodynamic compromise. • Risk factors associated with the risk of bleeding include operator experience, needle diameter, and the number of liver biopsy passes taken. 1. Gilmore IT, Burroughs A, Murray-Lyon IM, et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut 1995;36:437–41. 2. Forssell PL, Bronkowsky HL, Anderson PB, et al. Intrahepatic haematoma after aspiration liver biopsy: a prospective randomised controlled trial using two different needles. Dig Dis Sci 1981;26:631–5. 3. Perrault J, McGill DB, Ott BJ, et al. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978;74:103–6. 4. McGill DB, Rakela J, Zinsmeister AR, et al. A 21-year experience with major haemorrhage after percutaneous liver biopsy. Gastroenterology 1990;99:1396–400. 5. Knauer MC. Percutaneous biopsy of the liver as a procedure for outpatients. Gastroenterology 1978;74:101–2. 6. Minuk GY, Sutherland LR, Wiseman D, et al. Prospective study of the incidence of ultrasound-detected intrahepatic and subcapsular haematomas in patients randomized to 6 or 24 hours of bed rest after percutaneous liver biopsy. Gastroenterology 1987;92:290–3.
  52. 52. MORBIDITY • Puncture of other viscera occurs infrequently, with an incidence of between 0.01 and 0.1%.[1] The puncture of lung, colon, kidney and GB together with pneumothorax, pleural effusion, and subcutaneous emphysema are well recognised complications, which rarely require intervention.[2] • Other recognised complications include sepsis, reaction to the anaesthetic, breakage of the biopsy needle,[3] and intrahepatic arteriovenous fistulae.[4] • For other approaches, Riley and colleagues[5] reported one case of a fatal haemorrhage after a plugged liver biopsy in a series of 20 pts. 1. Piccininio F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. J Hepatol 1986;2:165–73. 2. Stotland BR, Lichtenstein GR. Liver biopsy complications and routine ultrasound.Am J Gastroenterol 1996;91:1295–6. 3. Lazar H. Fractured liver biopsy needles. Gastroenterology 1978;74:801. 4. Okuda K, Musha H, Nakajima Y, et al. Frequency of intrahepatic arteriovenous fistula as a sequelae to percutaneous needle puncture of the liver. Gastroenterology 1978;74:1204–7. 5. Riley SA, Ellis WR, Irving HC, et al. Percutaneous liver biopsy with plugging of needle track: a safe method for use in patients with impaired coagulation. Lancet 1984;ii:436.
  53. 53. Complication: Hematobilia • Hematobilia is an infrequent complication of liver biopsy occurring in 0.05 % of pts, presenting with the classic triad of GI bleeding manifesting as melena, biliary colic, and jaundice. • The bleeding can be arterial or venous and is generally delayed, with a mean onset of 5 days post procedure. • Endoscopy will reveal blood flowing from the ampulla of Vater and ERCP will demonstrate filling defects in the biliary tree and gallbladder. • Angiography and embolization is required to treat the bleeding vessel.
  54. 54. Complications of percutaneous biopsy Schiff
  55. 55. Transvenous liver biopsy Percutaneous Liver biopsy Transvenous (transjugular) Liver biopsy source©2015 Boston Scientific Corporation or its affiliates.
  56. 56. Transvenous liver biopsy • TVLB is usually performed via the transjugular route from within the vascular system in order to reduce the risk of bleeding. • Percutaneous liver biopsy is generally avoided in pts with platelet count <60 000/m3, PT >4 seconds above control, an INRI >1.5, and in these cases, the pnt should be considered for TVLB. • In addition, TVLB is performed when pts have ascites and when peliosis hepatis is suspected.
  57. 57. Transvenous liver biopsy • The right internal jugular vein is punctured using US guidance and a catheter is advanced under fluoroscopy to the hepatic vein and a liver specimen is obtained by advancing a needle through the vein wall and into the hepatic parenchyma. • Adequate specimens can be obtained in 80–100% of cases but biopsies are typically smaller than those obtained by the percutaneous route. • An added advantage of a transvenous liver biopsy is the ability to perform hepatic venous pressure gradient measurements for assessment of portal HTN. • Contraindications are rare but the Society of Interventional Radiology guidelines suggest that additional blood products are administered for an INR >2.5 and a platelet count of <50 000/mm3. • Note: if u require detailed information in TJLB , pls request. thankx
  58. 58. Complications in Transvenous liver biopsy • The complication rate after transvenous liver biopsy is low and ranges from 0.13 to 6.5%. The majority of complications are mild and related to bleeding from the puncture site over the venous access. Minor complications also include cardiac arrhythmia, and pneumothorax. • Major complications are reported in 0.6% of cases after a transvenous liver biopsy and include major hemorrhage from a capsular perforation. Mortality rate is reported in <0.1% for adults and 0.1% for children. Minor complications include cardiac arrhythmia, pain or hematoma at the puncture site over the jugular vein and pneumothorax . 1. Lebrec D, Goldfarb G, Degott C, et al. Transvenous liver biopsy. Gastroenterology 1982;83:338–40. Lebrec and colleagues,[1] in an analysis of 1000 transvenous LB, reported one death resulting from perforation of the liver capsule, and perforation of the liver capsule in 5, haematoma at the site of cannulation in 10, pneumothorax in 2, transient supraventricular tachycardia in six, and abdominal pain in 74 pts.
  59. 59. Transjugular liver biopsy: Summary Shyamkumar, et al.: Transjugular liver biopsy
  60. 60. Transjugular liver biopsy: what to do? Shyamkumar, et al.: Transjugular liver biopsy
  61. 61. Transjugular liver biopsy: what not to do? Shyamkumar, et al.: Transjugular liver biopsy
  62. 62. Endoscopic US-guided transgastric liver biopsy • EUS-LB is an emerging method that has shown promise in terms of tissue yield and procedural safety. • EUS provides a high-resolution image of both lobes of the liver, and a biopsy needle can be safely directed into the liver for sampling under image guidance. • Biopsies can be obtained from the right and left lobe at the same procedure and multiple biopsies can be obtained. • In a recent series of 110 pts who underwent EUS-LB, the median aggregate length of liver tissue obtained was 38mm and the median number of complete portal tracts was 14. [1] • This technique would be beneficial in pts who are undergoing upper GI endoscopy for a concomitant or related condition who would benefit from a liver biopsy. 1. Diehl DL, Johal AS, Khara HS, et al. Endoscopic ultrasoundguided liver biopsy: a multicenter experience. Endosc Int Open 2015;3(3):E210–15.
  63. 63. Endoscopic US-guided transgastric liver biopsy source©2015 Boston Scientific Corporation or its affiliates.
  64. 64. EUS-guided transgastric liver biopsy: right lobe access source©2015 Boston Scientific Corporation or its affiliates.
  65. 65. source©2015 Boston Scientific Corporation or its affiliates.
  66. 66. Laparoscopy of the liver and laparoscopic liver BX • It was initially introduced by Dimitri Ott, Georg Kelling, and Hans Christian Jacobeus. • Kelling performed the first laparoscopic procedure in dogs in 1901 and Jacobeus performed the first laparoscopic operation in humans in 1910. • In the following decades, the approach was developed further and eventually the familiar and essential camera was added. • Prior to this addition, the laparoscopy was a surgical approach with few applications.
  67. 67. • Diagnostic laparoscopy is a unique procedure to clearly classify parenchymal liver disease, staging of cancer, and an evaluation of peritoneal disease (i.e. ascites, total bilirubin, and metastatic disease to the parietal or visceral peritoneum of unknown etiology). • The major advantage of laparoscopy is that it allows the operator to visualize the liver and clearly characterize the liver surface and edge, obtain directed biopsy, view its subtle changes as well as gross appearance, which may be significantly different from imaging studies. • In the present era, laparoscopy is important in establishing the degree of fibrosis and cirrhosis. Laparoscopy of the liver and laparoscopic liver BX
  68. 68. Laparoscopic liver biopsy • Diagnostic laparoscopy is a safe and valuable procedure in the evaluation of chronic liver disease, as demonstrated by Vargas et al.[1] in an evaluation of 1794 pt records. • A definitive diagnosis was made in 91% of cases, with biopsy performed in 93%. • Chronic liver disease was evaluated in 890 pts, and a diagnosis was made in 98%. • 437 pts were evaluated for suspected primary or metastatic carcinoma, and a diagnosis was made in 85%. • Ascites was evaluated in 73 pts, and a diagnosis was made in 82%. • 164 pts were evaluated for abnormal LFTs, and a diagnosis was made in 91%. • HIV-related LFT abnormalities were evaluated in 67 pts, and a DX was made in 81%. • 163 pts underwent diagnostic laparoscopy for the evaluation of hepatomegaly, splenomegaly, unexplained portal HTN, FUO, and cholestasis, and a diagnosis was made in 74% of cases. 1. Vargas C, Jeffers LJ, Bernstein D, et al. Diagnostic laparoscopy: a 5-year experience in a hepatology training program. Am J Gastroenterol 1995;90(8):1258–62.
  69. 69. Laparoscopic liver biopsy • Laparoscopy has been shown to enhance diagnostic yield not only in the case of cirrhosis, but in other disorders as well. • Crantock et al.[1] reported on 200 consecutive pts who underwent laparoscopy and biopsy. • 25 pts had a malignancy diagnosed by the laparoscopic-guided biopsy, 8 of which were not seen on ultrasound prior to the laparoscopy. When compared with traditional histology, laparoscopy had >94% sensitivity and specificity at diagnosing fatty change, fibrosis, and inflammatory activity . 1. Crantock LR, Dillon JF, Hayes PC. Diagnostic laparoscopy and liver disease: experience of 200 cases. Aust N Z J Med 1994;24(3): 258–62.
  70. 70. Indications for laparoscopic liver biopsy. • Biopsy in pts with coagulopathy and/thrombocytopenia • Inadequate percutaneous biopsy • Biopsy of discrete lesions difficult to access percutaneously • Stage for primary hepatic tumors and gastric cancer • When other less invasive modalities fail to provide a diagnosis of liver disease • Evaluation of: – Unexplained hepatomegaly – Ascites – Peritoneal disease – Unexplained portal hypertension – Budd–Chiari syndrome – The obese patient’s liver disease – Liver disease after nondiagnostic radiological evaluation – Granulomatous disease SCHIFF
  71. 71. laparoscopic liver biopsy: procedure • Previously, pts undergoing diagnostic laparoscopic procedures were required to be admitted for observation after the procedure. Currently, outpatient diagnostic laparoscopy using conscious sedation has been demonstrated to be safe and effective. Patients should receive oxygen via a nasal cannula and should be monitored during the procedure. Intravenous access is required to provide conscious sedation. With the pt in a supine position, the abdomen is prepped and draped. • A Veress needle and trocar are usually placed in the left paramedian area; however, a right paramedian or subumbilical approach can be used in pts with an enlarged left hepatic lobe, splenomegaly, or previous splenectomy and thus, the laparoscopist has to have an excellent knowledge of the anatomy of the abdominal wall prior to the insertion of the laparoscope to avoid large vessels. • A local anesthetic such as 1% lidocaine is injected intradermally 2 cm above and to the left of the umbilicus. Then, a 16- gauge needle is inserted through the center of the wheal to the parietal peritoneum, which usually provokes some pain. Approximately 15–20mL of 1% lidocaine is applied to the subcutaneous tissue and fascia within a 2 cm radius.
  72. 72. laparoscopic liver biopsy: procedure • It is important that sufficient local anesthesia be applied. • A small incision is made in the center of the wheal, and the pt is asked to distend the abdominal cavity without arching the back. Aspiration with the 10mL syringe may avoid air embolism or inadvertent entry into the intestines, both of which are rare complications. • Whereas carbon dioxide used for insufflation during therapeutic laparoscopy is a peritoneal irritant and provokes pain, the nitrous oxide commonly used for diagnostic laparoscopy is better tolerated. • Insufflation to an abdominal cavity pressure of 20mmHg is accomplished by delivering 3–6 L of nitrous oxide through the Veress needle. A 20mL syringe, half filled with saline solution, is then inserted and rotated within the abdominal cavity. • Gas bubbles within the syringe indicate an unobstructed area for trocar placement. The patient is then instructed to distend the abdomen, and the trocar is inserted into the peritoneal cavity. Two distinct “pops” confirm placement. • An oblique-view laparoscope is then inserted into the abdominal cavity under direct vision. The area perpendicular to the scope is inspected for insertion-related damage. • With the pt in the Trendelenburg position, the bladder and other pelvic structures can be visualized.
  73. 73. laparoscopic liver biopsy: procedure • Placement of the patient in the reverse Trendelenburg position allows inspection of the right and left upper quadrants. • A second trocar is inserted into the right midclavicular line to allow, via another laparoscope, inspection of the superior aspect of the right lobe and the delivery of accessory equipment, such as the biopsy needle and palpating probe. • Liver specimens are obtained with a biopsy gun, or less commonly, a Tru-Cut needle from left of the falciform ligament, and the medial and lateral aspects of the right lobe to avoid sampling error. • To avoid large blood vessels, a tangential approach to the liver left of the falciform ligament is recommended. • Pressure is applied with a palpating probe on both the biopsy sites to tamponade the bleeding site and establish hemostasis. • Towards the end of the procedure, the initial trocar site (left of the umbilicus) is observed using the laparoscopic camera on the right side to look for any bleeding while the trocar is being removed. • If bleeding occurs at the initial trocar site, an Avotin pellet(?) is inserted into the site to achieve hemostasis.
  74. 74. laparoscopic liver biopsy: procedure • After the examination is completed, the trocar and biopsy sites can be closed with Steri-Strips or by sutures if a larger incision is made to accommodate larger trocars and laparoscopes. • Patients are observed for approximately 18–24 hours post procedure and discharged to resume regular activity in 3–4 days. • Right shoulder pain for 6–8 hours after the procedure is common.
  75. 75. • As with the percutaneous and transvenous biopsy approaches, pts should avoid NSAID and salicylate compounds for a period of time before and after the procedure. • Recommendations for pts with clotting factor and platelet count abnormalities are similar to those for percutaneous liver biopsy. • Advances in technology have allowed for the use of mini-laparoscopy, in which a smaller diameter trocar (1.9mm) is used. This technique has been noted to be extremely safe, less invasive, and well tolerated by pts. When compared with conventional laparoscopy, the mini-laparoscopic technique demonstrated similar success and had the advantage of a shorter procedure time. When compared with a percutaneous approach, mini-laparoscopy has been noted to have the advantage of offering both macroscopic and histologic results that can improve the diagnosis of cirrhosis. • Moreover, mini-laparoscopy appeared safe in a small study of 61 patients with a platelet count <50 000 /μL and/or an INR >1.5; however, most pts required the application of APC directly to the liver to stop post-biopsy bleeding.
  76. 76. Laparoscopic ultrasound • Laparoscopic ultrasonography is another technologic advance that has allowed for improved visualization of the liver parenchyma, targeted biopsies, and staging of both primary and metastatic hepatic lesions. • Performance of laparoscopic ultrasound can help to identify lesions not seen on conventional preoperative imaging and in this regard, has been noted to help in avoiding unnecessary laparotomy. • Therapeutically, laparoscopic ultrasound can be used to direct radiofrequency ablation of unresectable lesions.
  77. 77. EXTRA NOTES • Although there are few to no training programs teaching the diagnostic laparoscopy method for gastroenterologists and hepatologists, laparoscopies still remain an invaluable tool in diagnosing the stage of liver, gastric, and pancreatic cancer, as well as the diagnosis of parenchymal liver disease and ascites. • Other types of diagnostic procedures, such as percutaneous and transvenous biopsy, are associated with significant sampling error, particularly in this decade in patients with fatty liver or NASH. • An exciting and recent technical advance involves an extension of the natural orifice transluminal endoscopic surgery (NOTES) procedure to perform a liver biopsy.
  78. 78. Complications of diagnostic laparoscopy • In a large series of 1794 diagnostic laparoscopies, major complications occurred in only 8 pts (0.44%), minor complications were observed in 31 patients (1.73%), and there was one reported patient death.
  79. 79. AASLD Recommendations: Grading System for Recommendations
  80. 80. AASLD Recommendations: Summary 1. LB should be considered in pts in whom DX is in question, and when knowledge of a specific diagnosis is likely to alter the MX plan (Class I, Level B). 2. Liver histology is an important adjunct in the management of pts with known liver disease, particularly in situations where (prognostic) information about fibrosis stage may guide subsequent treatment; the decision to perform LB in these situations should be closely tied to consideration of the risks and benefits of the procedure (Class I, Level B). 3. Prior to performance of LB, pts should be educated about their liver disease and about investigations other than LB (if any) that may also provide diagnostic and prognostic information (Class I, Level C). 4. Prior to performance of LB, pts must be carefully informed about the procedure itself including alternatives, risks, benefits, and limitations; written informed consent should be obtained (Class I, Level C).
  81. 81. AASLD Recommendations: Summary 5. Antiplatelet medications should be discontinued several to 10 days before LB, although there is uncertainty surrounding the need for their discontinuation. Management of specific compounds should be handled on a case-by-case basis, taking into account their clinical indications, as well as the potential bleeding risk associated with their use in the setting of liver biopsy (Class I, Level C). 6. Anticoagulant medications should be discontinued prior to liver biopsy. Warfarin should generally be discontinued at least 5 days prior to LB. Heparin and related products should be discontinued 12-24 hours prior to biopsy. In all pts, the risk of discontinuing anticoagulant medications must be weighed against the (potential) risk of bleeding during/after liver biopsy (Class I, Level C). 7. Antiplatelet therapy may be restarted 48-72 hours after LB (Class I, Level C). 8. Warfarin may be restarted the day following liver biopsy (Class I, Level C).
  82. 82. AASLD Recommendations: Summary 9. Performance of LB requires an adequate sized and dedicated physical space suitable for focused physician effort as well as safe pt recovery (Class I, Level C). 10. The use of sedation, preferably light sedation, is safe and does not lead to increased procedural risk (Class IIb, Level B). 11. Vital signs must be frequently monitored (at least every 15 minutes for the first hour) after LB (Class I, Level C). 12. The recommended observation time after biopsy is between 2 to 4 hours and will vary depending on local expertise and practice (Class I, Level B). 13. US guidance with marking of the optimal biopsy site performed immediately preceding biopsy, by the individual performing the biopsy, is preferred, though not mandatory, because it likely reduces the risk of complications from LB (Class I, Level B). 14. Percutaneous LB with or without image guidance is appropriate only in cooperative pts, and this technique should not be utilized in uncooperative pts (Class I, Level C). 15. Uncooperative pts who require liver biopsy should undergo the procedure under general anesthesia or via the transvenous route (Class I, Level C).
  83. 83. AASLD Recommendations: Summary 16. In pts with clinically evident ascites requiring a LB, a transvenous approach is generally recommended, although percutaneous biopsy (after removal of ascites) or laparoscopic biopsy are acceptable alternatives (Class I, Level C). 17. Pts who require LB and who have a large vascular lesion identified on imaging should undergo the procedure using real-time image guidance (Class I, Level C). 18. The decision to perform LB in the setting of abnormal laboratory parameters of hemostasis should continue to be reached as the result of local practice(s) and consideration of the risks and benefits of LB because there is no specific PT-INR and/or platelet count cutoff at or above which potentially adverse bleeding can be reliably predicted (Class I, Level C). 19. Those performing LB must be cognizant of multiple potential complications (including death) that may occur after LB and discuss these appropriately with their pts before (Class I, Level C). 20. Platelet transfusion should be considered when levels are <50,000-60,000/mL (this applies whether one is attempting biopsy transcutaneously or transvenously) (Class I, Level C). 21. 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).
  84. 84. AASLD Recommendations: Summary 22. In pts with renal failure or on hemodialysis, desmopressin (DDAVP) may be considered, although its use appears to be unnecessary in pts on stable dialysis regimens (Class IIa, Level B). 23. Pts on chronic hemodialysis should be well dialyzed prior to LB, and heparin should be avoided if at all possible (Class I, Level C). 24. Image-guided LB is recommended in certain clinical situations including in pts with known intrahepatic lesions (real-time imaging is strongly preferred) and in those with previous intraabdominal surgery who may have adhesions. Image guided LB should also be considered in the following situations: pts with small livers that are difficult to percuss, obese pts, and pts with clinically evident ascites (Class I, Level C). 25. Because diagnosis, grading, and staging of non-neoplastic, diffuse parenchymal liver disease is dependent on an adequate sized biopsy, a biopsy of at least 2-3 cm in length and 16-gauge in caliber is recommended (Class I, Level C). 26. It is recommended that if applicable, the presence of fewer than 11 complete portal tracts be noted in the pathology report, with recognition that diagnosis, grading, and staging may be incorrect due to an insufficient sample size (Class I, Level C).
  85. 85. AASLD Recommendations: Summary 27. If cirrhosis is suspected, a cutting rather than a suction needle is recommended (Class I, Level B). 28. In clinical practice, use of a simple (e.g., Metavir or Batts-Ludwig) rather than complex (e.g., Ishak) scoring system is recommended (Class I, Level C). 29. LB 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) 30. Specific training for LB is essential and is recommended for those who perform it (Class I,Level C). 31. LB should be taught to trainees by experts, highly experienced in the practice of liver biopsy and management of its potential complications (Class I, Level C). 32. Although the number of biopsies required to become adequately trained is unknown, it is recommended that operators perform at least 40 biopsies (Class I, Level C) 33. Training in percutaneous liver biopsy should include specific training in ultrasound interpretation of fundamental liver anatomy and other landmarks (Class I, Level C). 34. Image-guided liver biopsy should be taught to trainees by experts who themselves have adequate training and experience with the technique (Class I,Level C).
  86. 86. References • Schiff's Diseases of the Liver, 12th Edition • Medscape • Uptodate • Other references are included in corresponding slides • AASLD GUIDELINES

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