New York Pathological Society presentation on "Viral Hepatitis Biopsy Assessment in the Treatment Era: The Beijing Classification"

1. Viral Hepatitis Biopsy Assessment in the Treatment Era:
The Beijing Classification
Neil Theise, MD
Department of Pathology
New York University School of Medicine
New York City

2. Clinical problems, 1968:
 Hepatitis B
 Autoimmune hepatitis
=> Biopsy for assessment of prognosis: CAH, CPH
Clinical problems, 1990’s:
 Hepatitis C
 Mixed viral infections
=> Biopsy for assessment of Tx needs:
Ishak, modified Ishak, Batts-Ludwig, Metavir
Clinical problems, 2016:
 Successful antiviral therapies
 Non-alcoholic fatty liver disease (NAFLD)
=> Biopsy of advanced (cirrhotic) stage liver
for assessment of prognosis: Laennec…?

3. RecoveryDeath/Transplant
Chronic Hepatitis
CPH CAH CLH

4. RecoveryDeath/Transplant
Chronic Hepatitis
CPH CAH CLH
Cirrhosis
Progression
Unlikely

5. RecoveryDeath/Transplant
Chronic Hepatitis
CPH CAH CLH
Cirrhosis
Progression
Unlikely

6. Clinical problems, 1968:
 Hepatitis B
 Autoimmune hepatitis
=> Biopsy for assessment of prognosis: CAH, CPH
Clinical problems, 1990’s:
 Hepatitis C
 Mixed viral infections
=> Biopsy for assessment of Tx needs:
Ishak, modified Ishak, Batts-Ludwig, Metavir
Clinical problems, 2016:
 Successful antiviral therapies
 Non-alcoholic fatty liver disease (NAFLD)
=> Biopsy of advanced (cirrhotic) stage liver
for assessment of prognosis: Laennec…?

7. RecoveryDeath/Transplant
Chronic Hepatitis
STAGING
Of
Progression
GRADING
Of
Activity

8. Stages of Fibrosis
Ishak
5 61 2
focal frequent
1 2 3 4
Portal
Fibosis
Fibrous
Septa
Transition
to Cirrhosis
Cirrhosis
1 42 3
focal frequent
Metavir
Theise ND. Human Pathology 2007
Modified Ishak  Batts-Ludwig
3 4
focal frequent

9. Stages of Fibrosis
Ishak
5 61 2
focal frequent
1 2 3 4
Portal
Fibosis
Fibrous
Septa
Transition
to Cirrhosis
Cirrhosis
1 42 3
focal frequent
Metavir
Theise ND. Human Pathology 2007
Modified Ishak  Batts-Ludwig
3 4
focal frequent

10. Clinical problems, 1968:
 Hepatitis B
 Autoimmune hepatitis
=> Biopsy for assessment of prognosis: CAH, CPH
Clinical problems, 1990’s:
 Hepatitis C
 Mixed viral infections
=> Biopsy for assessment of Tx needs:
Ishak, modified Ishak, Batts-Ludwig, Metavir
Clinical problems, 2016:
 Successful antiviral therapies
=> ?

11. Clinical problems, 1968:
 Hepatitis B
 Autoimmune hepatitis
=> Biopsy for assessment of prognosis: CAH, CPH
Clinical problems, 1990’s:
 Hepatitis C
 Mixed viral infections
=> Biopsy for assessment of Tx needs:
Ishak, modified Ishak, Batts-Ludwig, Metavir
Clinical problems, 2016:
 Successful antiviral therapies
=> Biopsy of advanced (cirrhotic) stage liver
for assessment of prognosis

12. …but not all cirrhosis is the same…

13. Fig. 1.
Classification of chronic liver disease based on histological, clinical, hemodynamic, and
biological parameters. In the noncirrhotic stage (METAVIR F1–F3), there is no clinical
evidence of cirrhosis, the HVPG is below 6 mmHg, and at this stage there is fibrogenesis and
neovascularization. The cirrhotic stage (METAVIR F4) is broadly classified into two stages:
compensated and decompensated, with clinical decompensation being defined by the
development of ascites, variceal hemorrhage (VH), encephalopathy, and jaundice. Within the
compensated stage, patients can be subclassified into those without varices (stage 1) and those
with varices (stage 2). Those without varices can be further subclassified into those with an
Garcia-Tsao et al. Page 8
NIH-PAAuthorManuscriptNIH-PAAuthorManusc
Garcia-Tsao, Friedman, Iredale and Pinzani.
Now there are many (stages) where before there was one: in search of a pathophysiological
classification of cirrhosis.
Hepatology 2010: 51(4):1445-49

14. Fig. 1.
Classification of chronic liver disease based on histological, clinical, hemodynamic, and
biological parameters. In the noncirrhotic stage (METAVIR F1–F3), there is no clinical
evidence of cirrhosis, the HVPG is below 6 mmHg, and at this stage there is fibrogenesis and
neovascularization. The cirrhotic stage (METAVIR F4) is broadly classified into two stages:
compensated and decompensated, with clinical decompensation being defined by the
development of ascites, variceal hemorrhage (VH), encephalopathy, and jaundice. Within the
compensated stage, patients can be subclassified into those without varices (stage 1) and those
with varices (stage 2). Those without varices can be further subclassified into those with an
Garcia-Tsao et al. Page 8
NIH-PAAuthorManuscriptNIH-PAAuthorManusc
Garcia-Tsao, Friedman, Iredale and Pinzani.
Now there are many (stages) where before there was one: in search of a pathophysiological
classification of cirrhosis.
Hepatology 2010: 51(4):1445-49
Ishak 5-6Ishak 1-4

15. …but not all cirrhosis is the same…
The Laennec Staging System

16. Kim et al. Histological sub-classification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical
stage and grade of portal hypertension. Journal of Hepatology 2011;55:1004-09.

17. What about regression of cirrhosis?

18. Wanless, Nakashima and Sherman.
Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis.
Arch Pathol Lab Med 2000;124:1599

19. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

20. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibres
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

22. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

24. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

25. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

27. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration i.e. “hepatocyte ‘buds”

29. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibers
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins

31. Hepatic Repair Complex
1. Fragmentation and regression of scar
A. delicate, perforated septa
B. isolated thick collagen fibres
C. delicate, periportal fibrous spikes
D. hepatocytes within or splitting septa
2. Evidence of prior, now resolving, vascular derangements
A. portal tract remnants,
B. hepatic vein remnants with prolapsed hepatocytes
C. aberrant parenchymal veins
3. Parenchymal regeneration, i.e. “hepatocyte buds”

32. Active
Alcohol Use

33. Active
Alcohol Use
> 6 months
abstinence

34. Active
Alcohol Use
> 6 months
abstinence
4 years
abstinence

36. A

37. B

38. C

39. D
*

40. Kim et al. Histological sub-classification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical
stage and grade of portal hypertension. Journal of Hepatology 2011;55:1004-09.

41. Interim Conclusions
• We need a new staging system for assessment of
advanced stage (cirrhotic) liver diseases

42. Interim Conclusions
• We need a new staging system for assessment of
advanced stage (cirrhotic) liver diseases
• The system must be able to distinguish and quantify
features of regression vs. progression.

43. Interim Conclusions
• We need a new staging system for assessment of
advanced stage (cirrhotic) liver diseases
• The system must be able to distinguish and quantify
features of regression vs. progression.
• The new system must be prognostic, predicting who
will resolve back to a normal liver after successful
curative treatment or long term disease suppression.

60. GRADING
Of
Activity
• Portal inflammation
• Interface hepatitis
• Lobular hepatitis
• Confluent necrosis

61. Confluent
Necrosis

62. Confluent
Necrosis

63. Confluent
Necrosis

65. Bridging confluent necrosis

66. Confluent necrosis in HBV, think about:
- HBeAg to Ab conversion
- HDV super-infection on HBV
- HIV co-infection
- Autoimmune hepatitis
- Drug/toxin induced injury, as always

67. Confluent necrosis in HCV, think about:
- HCV acute exacerbation
- HIV co-infection
- Autoimmune hepatitis
- Drug/toxin induced injury, as always

69. Am J Clin Patho 2012; 137: 5-9