Basic patterns of liver damage what information can a liver biopsy provide and what clinical information does the pathologist need?

Transcription

1 Basic patterns of liver damage what information can a liver biopsy provide and what clinical information does the pathologist need? Rob Goldin

2 FATTY LIVER DISEASE Brunt EM Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation. Hepatol Commun Jun 7;1(5):

3 Types of fatty change: Large droplet

4 Types of fatty change: Small droplet

5 Fatty liver disease: Ballooning and inflammation

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7 Hepatology Nov 1;56(5): Recognising ballooning (B) Normal hepatocytes, ballooning, grade 0. Cytoplasm is pink and granular and liver cells have sharp angles. (C) Ballooning, grade 1. Hepatocytes have rounded contours with clear reticular cytoplasm. Size is quite similar to that of normal hepatocytes. (D) Ballooning, grade 2. Cells are rounded with clear cytoplasm and twice as large as normal hepatocytes.

8 Nuclear vacuolation

9 Predicting Response to Treatment in Alcoholic Hepatitis Stage of fibrosis No fibrosis or portal fibrosis 0 Expansive fibrosis 0 Bridging fibrosis or cirrhosis +3 Bilirubinostasis No 0 Hepatocellular only 0 Canalicular or ductular +1 Canalicular or ductular plus hepatocellular PMN infiltration Points +2 No/Mild +2 Severe 0 Megamitochondria No megamitochondria +2 Megamitochondria 0 The AHHS categories are as follows: mild, 0 3; intermediate, 4 5; severe, 6 9. Gastroenterology May 1;146(5):

10 ( A ) Hepatocellular and canalicular bilirubinostasis ( arrow ). ( B ) Ductular bilirubinostasis ( arrow ). ( C ) Megamitochondria ( arrows ).

11 Steatosis grade NAFLD Activity Score Lobular inflammation Hepatocellular ballooning 0: <5% 0: None 0: None 1: 5-33% 1:<2 foci/20x field 1: Mild, few 2: 34-66% 2: 2-4 foci/20x field 3: >66% 3: >4 foci/20x field NAFLD activity score (NAS): 0-8 Steatosis (0-3) + Lobular Inflammation (0-3) 2: Moderate marked, many + Ballooning (0-2) Hepatology Mar; 53(3):

12 CHRONIC HEPATITIS

13 Assess disease severity: Grade (necro-inflammation) Stage (fibrosis)? Score (using modified Histological Activity Index / METAVIR) Assess disease progression or response to treatment Exclude co-existing liver diseases

14 CHRONIC VIRAL HEPATITIS Misdraji J. Changing indications for liver biopsy: viral hepatitis. Diagnostic Histopathology Mar 1;20(3):

15 German AL et al. Can reference images improve interobserver agreement in reporting liver fibrosis?. Journal of Clinical Pathology Nov 10:jclinpath-2017.

16 HBV: Ground glass hepatocytes Orcein

17 Liver Biopsy in HBV The natural history of hepatitis B is complex, and HBeAg status, ALT level, and HBV DNA level are necessary to discriminate between the various phases, but sometimes these tests are inconclusive. Liver biopsy has become more important in the determination of disease activity in patients with hepatitis B with the understanding that patients with normal ALT may have significant inflammation or fibrosis. Immunohistochemistry for HBsAg and HBcAg is not recommended for the routine evaluation of patients with chronic hepatitis B, but it can provide information on viral replication and disease phase in selected cases.

18 HCV: Lymphoid aggregate/follicle

19 HCV: Hepatitic bile duct damage

20 HCV genotype 3: Fatty change

21 Liver Biopsy in HCV Increasingly, the information derived from determining HCV genotype and IL-28B genotype is defining which patients should be treated or not, regardless of the information a liver biopsy might provide, reducing the need to biopsy patients with hepatitis C. The introduction of direct-acting antiviral agents and the imminent development of interferon free regimens will probably reduce the need for liver biopsy in hepatitis C, as the high rate of sustained viral response makes the decision to treat less reliant on the stage of disease.

22 HDV

23 AUTOIMMUNE HEPATITIS Balitzer D, Shafizadeh N, Peters MG, Ferrell LD, Alshak N, Kakar S. Autoimmune hepatitis: review of histologic features included in the simplified criteria proposed by the international autoimmune hepatitis group and proposal for new histologic criteria. Modern Pathology May;30(5):773.

24 Autoimmune hepatitis Help in making the diagnosis Help in assessing the response to treatment

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26 Simplified histological criteria for the diagnosis of AIH

27 DRUG INDUCED LIVER INJURY Kleiner DE. The histopathological evaluation of drug induced liver injury. Histopathology Jan 1;70(1):81-93.

28 Any kind of liver disease can be caused by a drug Histological features suggesting a drug reaction: Eosinophils, plasma cells, granulomas, sharply demarcated necrosis, cholestatic hepatitis

29 Drug reaction

30 Drug reaction

31 Drug reaction

32 Histological predictors of severity in drug-induced liver disease. More severe disease associated with: 1. necrosis 2. fibrosis stage 3. microvesicular steatosis 4. cholangiolar cholestasis 5. bile duct damage Milder disease associated with: 1. granulomas 2. increased eosinophils

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35 BILIARY TRACT DISEASE Lewis J. Pathological patterns of biliary disease. Clinical Liver Disease Nov 1;10(5):

36 Causes of Disappearing Bile Ducts PBC (and its variants) PSC (and its variants) Drugs and Toxins Chronic transplant rejection Graft Vs. Host Hodgkin s Disease, Histiocytosis X Sarcoid Paucity of interlobular bile ducts HIV Idiopathic

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38 Biliary tract disease: Orcein stain

39 Biliary tract disease: Keratin7

40 Primary Biliary Cholangitis

41 PSC

42 Specific features for IgG4-related cholangiopathy IgG4 Disease IgG4+ plasma cells (>10/hpf) IgG4+/IgG+ cell ratio >40%

43 Grading and Staging of Biliary Duct Disease Grading: hepatitis and cholangitis Staging: fibrosis, copper binding accumulation and duct loss Hepatology Mar 1;65(3):

44 VASCULAR DISEASE Semela D. Systemic disease associated with noncirrhotic portal hypertension. Clinical Liver Disease Oct 1;6(4):103-6.

45 Nodular regenerative hyperplasia

46 Budd-Chiari Syndrome

47 Causes of Nodular Regenerative Hyperplasia Connective tissue disorders Myeloproliferative disorders Chronic vascular congestion Drugs e.g. steroids, anticancer drugs, anticonvulsants, immunosuppressive agents

48 DISCREPANCY RATES IN LIVER BIOPSY REPORTING Paterson AL, Allison ME, Brais R, Davies SE. Any value in a specialist review of liver biopsies? Conclusions of a 4 year review. Histopathology Aug 1;69(2):

49 fibrosis staging recognising and interpreting bile duct disorders misdiagnoses of autoimmune hepatitis second diagnoses

50 Second diagnoses fatty liver disease hepatocyte iron alpha-1 antitrypsin deficiency Modern Pathology Jan;16(1):49.

51 Regressed cholangiocarcinoma

52 Hepatocyte iron

53 Normal Liver Czeczok TW, Van Arnam JS, Wood LD, Torbenson MS, Mounajjed T. The Almost-Normal Liver Biopsy: Presentation, Clinical Associations, and Outcome. The American Journal of Surgical Pathology Sep 1;41(9):

54 Normal Liver: Conditions to Exclude

55 Normal Liver: What happened next Seven patients (7.2% patients ) eventually developed chronic liver disease: autoimmune hepatitis [n=3], primary biliary cirrhosis [n=3], cryptogenic cirrhosis [n=1]).

56 WHAT CLINICAL INFORMATION DOES THE PATHOLOGIST NEED?

57 A decent clinical history!

58 Clinicians providing no clinical history! Pathologist asking clinicians to correlate!!