Hepatic and Inflammatory fibrosis (1)

Question 1

Histological scoring system: MEtavir:

Fibrosis

0:

1:

2:

Answer 1

O :no fibrosis

1: potential fibrosis; Portal fibrosis
2. Periportal fibrosis

Question 2

Histological scoring system: MEtavir:

Fibrosis

3:

4:

Answer 2

3: septal fibrosis; bridging fibrosis
4: cirrhosis

Question 3

Histological scoring system Metavir: Inflammation

0:

1:

2:

3:

4:

Answer 3

No inflammation

minimal inflammation

mild

moderate

severe

Question 5

What stain can we use to identify chrrhosis?

Answer 5

trichome stain

Question 6

• Acute cell death
 Fibrosis in most cases takes years
• Can lead to acute liver failure

Answer 6

Hepatic necrosis

Question 7

= acute liver failure
complicated by coagulopathy and
encephalopathy

Answer 7

Fulminant liver failure (seen in hepatic necrosis)

Question 8

• The most common causes of acute and
fulminant liver failure include

Answer 8

medications (acetaminophen) and viral hepatitis

Question 9

Content of alcohol

Beer:

Wine:

Hard:

Answer 9

Beer; 5% alcohol, 12oz serving, 13.8 g of alcohol

Wine: 12% alcohol, 4oz serving, 10.7 grams

Hard: 40% alcohol, 1.5 oz, 13.4 grams

Question 10

• Binge drinking
 For women, ____ drinks during a single
occasion
 For men, ____ drinks during a single occasion

Answer 10

4 or more

5 or more

Question 11

• Heavy drinking
 For women, more than ____per day on average
 For men, more than ____ heavy drinking,
binge drinking or both.

Answer 11

1 drink

2 drinks

Question 12

Ethenol –> Acetaldehyde via which enZ and CYP

Answer 12

Alcohol dehydrogenase by 75% and CYP2E1 for the other 25%

These are the Microsomal Ethanol Oxidizing System

(MEOS)

Question 13

Acetaldehyde–> Acetic Acid via

Answer 13

Aldehyde dehydrogenase

Question 14

Alcohol metoabolism results in: Increased NADH. What does this do to the TCA cycle

Answer 14

 inhibition of TCA cycle; reduced gluconeogenesis
 reduced fatty acid oxidation

Question 15

In alcohol metablisim, we see increased _______
 activates stellate cells to form collagen
 Microfilaments that maintain intracellular skeleton are sheared
 Kupffer cells produce tumor necrosis factor alpha
(TNF α)

Answer 15

Acetaldehyde

Question 16

produce tumor necrosis factor alpha (TNF α)

Answer 16

Kupffer cells

Question 17

What happens in pathogenesis of alcohol in sinusoids

Answer 17

vili are damaged

accumulate collagen from stellate cells in space of Disse

Activate kupfner cells to release cytokines

Question 18

What is the spectrum of disease in a patient with Alcoholic Liver Disease

Answer 18

Normal liver–> 90-100% fatty liver

fatty liver–> alcoholic hepatitis in 10-35% and then alcoholic hepatitis to cirrhosis

fatty liver–> cirrhosis in 8-20%

Question 19

What makes up the portal triad

Answer 19

branch of portal vein, branch of hepatic artery, branch of bile duct

Question 20

Do you have symptoms from having fatty liver from alcohol?

Answer 20

Not unless there is inflammation

Question 21

What does alcoholic hepatitis look like on histology?

Answer 21

lots of fat and inflammation; gets more fibrosis with continued drinking; as you lay down more scar tissues you lose fat adn gets replaced by scar tissue

Question 22

What are the 3 big risk factors for ALD?

Answer 22

• Quantity of Alcohol
 >30 g/day in men or >70 drinks a week big increase
 > 20 g/day in women; >28-40 drinks week big increase
• Outside of meals
• Binge drinking

Question 24

Alcoholic liver disease and Hepatitis C

Answer 24

Alcohol abuse increases how fast you progress to cirrhosis when you have Hep C. Normally should take 20-30 yrs, if you have Hep C and abuse alcohol, this occurs much faster

Question 25

What happens to the following in pts with ALD  AST/ALT  ALT  Alk Phos  Albumin  Bilirubin

Answer 25

 AST/ALT ratio \>2-3  ALT usually \<300 IU/ml  Rarely raised Alk Phos  Low Albumin  Bilirubin

Question 26

Hematology abnormalities in ALD

Answer 26

 Prolonged INR (advanced disease)  Macrocytosis / anemia  Thrombocytopenia (advanced disease)

Question 27

Treatment for Alcoholic Hepatitis

Answer 27

• Abstinence and lifestyle modification  nutritional support • Anti-inflammatory drugs  glucocorticoids  Pentoxifylline (inhibits TNFα) made in Kupfner

Question 29

What is the discriminant function and how do we use it?

Answer 29

4.6(PT-PT CONTROL) + T BILI • Patients with values \> 32 have a 1-month mortality from 30%-50% This is how we decide which alcoholic hepatitis pts to tx

Question 30

Dx?• 38 yo male with jaundice and malaise • ALT 29 • AST 96 • ALK PHOS 98 • TOTAL BILI 12 • DIRECT BILI 8 • PT 19 SEC • CONTROL PT 12 SEC

Answer 30

AST:ALT ( 96:29) apx 3:1 so alcoholic cirrohsis pt has Contorl PT of 19 sec and T bili of 12 4.6 (19-12) + 12 = 44 which is more then 32, needs tx!

Question 31

What happens to survival rates in pts with alcoholic hepatits when given glucocorticoids? what about when given Pentoxifylline for 28 days?

Answer 31

3 month survival increases from 45% to 85% and incresaes from 45% to 80%

Question 33

What does the 5 yr survival look like for pts with alcoholic cirrhosis and what is it based on?

Answer 33

Based on the Child-Turcotte-Pugh score 5-7: 60% 5 yr survival 8-10: 40% 5 yr survival 11-5: 20% 5 yr survival

Question 34

* First described in 1980 * 20 patients with biopsies consistent with alcoholic hepatitis * All denied alcohol use * Female, obese, diabetes mellitus * Now recognized as the most common cause of elevate transaminases in the U.S.

Answer 34

``` NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) ```

Question 35

What are the two categories of non-alcoholic fatty liver disease (NAFLD)

Answer 35

Non-alcoholic fatty liver (NAFL) Non-alcoholic steatohepatitis (NASH)

Question 36

``` o presence of hepatic steatosis without inflammation or hepatocellular injury (ballooning of hepatocytes) ```

Answer 36

Non-alcholoic fatty liver (NAFL)

Question 37

o Presence of hepatic steatosis and inflammation with hepatocellular injury (ballooning of hepatocytes) with or without fibrosis

Answer 37

 Non-alcoholic steatohepatitis (NASH)

Question 38

Prevalene of chronic liver disorders in the US

Answer 38

Non-alcoholic fatty liver is most prevelant in US and is in 25% of the population Nonalchoholic steatohepatitis is number 2

Question 39

STAGES IN THE PROGRESSION OF NON-ALCOHOLIC FATTY LIVER DISEASE

Answer 39

Fatty liver (Hepatosteatosis)--\> 10%--\> to Steahepatitis (NASH) --\> Steatohepatitis with Fibrosis (35% of NASH)--\> Cirrhosis (15% of NASH) \*small % devo cirrhosis but the starting % is HIGH at 20% of population having fatty liver hepatoseatosis

Question 40

PREVALENCE (%) OF INDIVIDUAL METABOLIC ABNORMALITIES OF THE METABOLIC SYNDROME AMONG US ADULTS AGED \>20 YEARS

Answer 40

Risk includes: abdominal obesity, hypertriglyceridemia, low HDL, High BP and high fasting glucose BMI over 30 is problematic and TGs are more concerning then cholesterol

Question 41

NAFLD association with metabolic syndrome

Answer 41

NAFLD seen in 30-100% pts that are Obese (BME\>30) seen in 15-50% with Diabetes seen in 15-80% with hypertriglyceridemia

Question 42

Non-Alcoholic Fatty Liver Disease increases with: seen in what pt population:

Answer 42

* Prevalence increases with age * Severity of disease (including advanced fibrosis/cirrhosis) increases with age * Males \> Females * Hispanics \> Caucasians \> African Americans

Question 43

Obesity has been increasing over the years in America leading to ______ being the most common reason for liver transplant

Answer 43

NAFLD

Question 44

Most common liver disease in children in US

Answer 44

NAFLD: increaes in prevelance with age more common in boys Hispanic \> Asian \> White \> Black \*\*\*18% of these kids have NASH

Question 45

•\_\_\_\_\_\_\_\_\_ rather than hypercholesteremia increases risk for NAFLD

Answer 45

Hypertriglyceridemia \*\*• 3-fold greater risk with triglycerides \>200

Question 46

Causes of Steatosis and Steatohepatitis

Answer 46

Insulin resistance, alcohol, abetalipoproteinemia meds: Amiodorone, steroids, HAART, Tamoxifen, Diltazem Nutrition (TPN, Severe Starvation, refeeding syndrome) Weigth changes; jejunoileal bypass and gastric bypass

Question 47

What is the progression and development of NAFLD; starting with increased oral intake and sedentary life style

Answer 47

(possible genetic influence)--\> become obese/HTN/Hyperlipidemia: Lead to Insulin resistance: causing normal--\> steatosis Oxidative stress further affects liver: steatosis --\> steatohepatitis --\> cirrhosis

Question 48

What does a fatty liver look like on ultrasound? On CT?

Answer 48

on ultrasound comes out BRIGHT WHITE (fat and nodules)--simple steatosis doesn' t cause this appearance On CT liver appears dark (vs light) and enlarged

Question 49

What do we target when treating NAFLD?

Answer 49

Treat insulin resistance that is from obesity/HTN/hyperlipidemia Treat the oxidative stress prevent pts becoming fat

Question 50

How much do we recommend pts to lose to have improved symtpoms if they have NAFLD

Answer 50

Loss of at least 3-5% of body weight necessary to improve steatosis but up to 10% may be needed to improve inflammation.

Question 51

2 tx for NASH and their effect on patient?

Answer 51

Treat NASH with Pioglitazone or Vitamen EEndpoint: improvement in histology score (steatosis, inflammation, ballooning degeneration and fibrosis) reduced transanimase reduced inflammation NEITHER reduced fibrosis

Question 52

What tx to patients gain more weight on for TX of NASH

Answer 52

Pioglitazone

Question 53

Pioglitazone can be used to treat patients with \_\_\_\_\_\_\_\_. The majority of patients that participated in clinical trials were nondiabetic and long-term safety and efficacy is not established.

Answer 53

biopsy-proven NASH

Question 54

improves liver histology in non-diabetic patients with biopsy-proven NASH and should be considered first-line therapy

Answer 54

• Vitamin E at a dose of 800 IU/day

Question 55

vitamin E is not recommended to treat NASH in what three pt populations

Answer 55

diabetic patients, NAFLD without liver biopsy, NASH cirrhosis or cryptogenic cirrhosis.