# Presentation: 293990

## Evaluation of Liver Histology in Clinical Trials for Chronic Viral Hepatitis 

- Zachary Goodman, M.D., Ph.D.
- Chief, Hepatic Pathology
- Armed Forces Institute of Pathology

## Chronic Viral HepatitisPresumed Pathogenesis 

**Chronic Viral Hepatitis****Presumed Pathogenesis**** **

**Immune Response**

**Tissue Damage**

**Scarring**

**HCC**

**Cirrhosis**

**Death**

**Histologic Evaluation**

## Hepatitis

- <date/time>

- Acute
- Chronic

- Hepatocellular Injury
-  Apoptosis
-  Focal “necrosis”
- Inflammation
-  Parenchymal
-  Portal
-  Periportal
- Repair and Regeneration
-   +/- Scarring

## Slide 4

## Slide 5

## Slide 6

## Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- <date/time>

- Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- Goal
-  To assess whether there is improvement in a cohort of patients treated with a new therapy in comparison to a control cohort

## Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- <date/time>

- Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- Methods
-  Semiquantitative numerical scoring
-  Ranked assessment
-  Single pathologist
-  Paired biopsies from each patient
-  Blinded as to treatment arm and order

## Histology Activity Index(Knodell Score)

- Periportal Injury		0-4
- Confluent Necrosis		0-6
- Parenchymal Injury		0-4
- Portal Inflammation		_0-4_
**Grade **(Inflammation)	0-18
**Stage** (Fibrosis)		0-4_ _

## Periportal Injury(Interface hepatitis, Piecemeal necrosis) 

**Mild = 1**

**Moderate = 3**
**(< 50% circ.)**

**Marked = 4**
**(> 50% circ.)**

**Periportal Injury****(Interface hepatitis, Piecemeal necrosis)**** **

## Slide 11

## Parenchymal Injury

**(<5 per 10X field)**

**Moderate = 3**
**(5-20 per 10X field)**

**Marked = 4**
**(>20 per 10X field)**

**Parenchymal Injury**

## Portal Inflammation

**Moderate = 3**

**Marked = 4**

**Portal Inflammation**

## Histology Activity Index(Knodell Score)

- Periportal Injury		0-4
- Confluent Necrosis		0-6
- Parenchymal Injury		0-4
- Portal Inflammation		_0-4_
**Grade **(Inflammation)	0-18
**Stage** (Fibrosis)		0-4_ _

## None = 0

**None = 0**

**Portal Fibrosis = 1**

**Bridging Fibrosis = 3**

**Cirrhosis = 4**

## Slide 16

## Fibrosis Scoring Methods

## Chronic Viral HepatitisHistologic Evaluation

**Grade (Activity, HAI score)**
**Correlates with ALT**
**Improves with successful therapy**
**Stage (Fibrosis)**
**Changes slowly**
**May improve with successful therapy**

## Paired biopsies from each patient
Blinded as to treatment arm and order
Inflammation (same, better, worse)
Fibrosis (same, better, worse)

**Blinded as to treatment arm and order**
**Inflammation (same, better, worse)**
**Fibrosis (same, better, worse)**

**Chronic Viral Hepatitis****Ranked Assessment**

## Slide 20

## Slide 21

## Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- <date/time>

- Chronic HepatitisHistologic Grading & Staging for Therapeutic Trials

- Primary Endpoint
-  Proportion of patients with 2 point improvement in HAI inflammation with no worsening of fibrosis score
- Other (Exploratory) Endpoints
-  Ranked assessment
-  Mean change in HAI
-  Other scoring systems