Hepatic and Inflammatory fibrosis (1) Flashcards
Histological scoring system: MEtavir:
Fibrosis
0:
1:
2:
O :no fibrosis
1: potential fibrosis; Portal fibrosis
2. Periportal fibrosis
Histological scoring system: MEtavir:
Fibrosis
3:
4:
3: septal fibrosis; bridging fibrosis
4: cirrhosis
Histological scoring system Metavir: Inflammation
0:
1:
2:
3:
4:
No inflammation
minimal inflammation
mild
moderate
severe
What stain can we use to identify chrrhosis?
trichome stain
• Acute cell death
Fibrosis in most cases takes years
• Can lead to acute liver failure
Hepatic necrosis
= acute liver failure
complicated by coagulopathy and
encephalopathy
Fulminant liver failure (seen in hepatic necrosis)
• The most common causes of acute and
fulminant liver failure include
medications (acetaminophen) and viral hepatitis
Content of alcohol
Beer:
Wine:
Hard:
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
• Binge drinking
For women, ____ drinks during a single
occasion
For men, ____ drinks during a single occasion
4 or more
5 or more
• Heavy drinking
For women, more than ____per day on average
For men, more than ____ heavy drinking,
binge drinking or both.
1 drink
2 drinks
Ethenol –> Acetaldehyde via which enZ and CYP
Alcohol dehydrogenase by 75% and CYP2E1 for the other 25%
These are the Microsomal Ethanol Oxidizing System
(MEOS)
Acetaldehyde–> Acetic Acid via
Aldehyde dehydrogenase
Alcohol metoabolism results in: Increased NADH. What does this do to the TCA cycle
inhibition of TCA cycle; reduced gluconeogenesis
reduced fatty acid oxidation
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)
Acetaldehyde
produce tumor necrosis factor alpha (TNF α)
Kupffer cells
What happens in pathogenesis of alcohol in sinusoids
vili are damaged
accumulate collagen from stellate cells in space of Disse
Activate kupfner cells to release cytokines
What is the spectrum of disease in a patient with Alcoholic Liver Disease
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%
What makes up the portal triad
branch of portal vein, branch of hepatic artery, branch of bile duct
Do you have symptoms from having fatty liver from alcohol?
Not unless there is inflammation
What does alcoholic hepatitis look like on histology?
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
What are the 3 big risk factors for ALD?
• 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
Alcoholic liver disease and Hepatitis C
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
What happens to the following in pts with ALD
AST/ALT
ALT
Alk Phos
Albumin
Bilirubin
AST/ALT ratio >2-3
ALT usually <300 IU/ml
Rarely raised Alk Phos
Low Albumin
Bilirubin
Hematology abnormalities in ALD
Prolonged INR
(advanced disease)
Macrocytosis / anemia
Thrombocytopenia
(advanced disease)
Treatment for Alcoholic Hepatitis
• Abstinence and lifestyle modification
nutritional support
• Anti-inflammatory drugs
glucocorticoids
Pentoxifylline (inhibits TNFα) made in Kupfner
What is the discriminant function and how do we use it?
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
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
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!
What happens to survival rates in pts with alcoholic hepatits when given glucocorticoids?
what about when given Pentoxifylline for 28 days?
3 month survival increases from 45% to 85%
and incresaes from 45% to 80%
What does the 5 yr survival look like for pts with alcoholic cirrhosis and what is it based on?
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
- 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.
NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
What are the two categories of non-alcoholic fatty liver disease (NAFLD)
Non-alcoholic fatty liver (NAFL)
Non-alcoholic steatohepatitis (NASH)
o presence of hepatic steatosis without inflammation or hepatocellular injury (ballooning of hepatocytes)
Non-alcholoic fatty liver (NAFL)
o Presence of hepatic steatosis and inflammation with hepatocellular injury (ballooning of hepatocytes) with or without fibrosis
Non-alcoholic steatohepatitis (NASH)
Prevalene of chronic liver disorders in the US
Non-alcoholic fatty liver is most prevelant in US and is in 25% of the population
Nonalchoholic steatohepatitis is number 2
STAGES IN THE PROGRESSION OF
NON-ALCOHOLIC FATTY LIVER DISEASE
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
PREVALENCE (%) OF INDIVIDUAL METABOLIC ABNORMALITIES
OF THE METABOLIC SYNDROME
AMONG US ADULTS AGED >20 YEARS
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
NAFLD association with metabolic syndrome
NAFLD seen in 30-100% pts that are Obese (BME>30)
seen in 15-50% with Diabetes
seen in 15-80% with hypertriglyceridemia
Non-Alcoholic Fatty Liver Disease increases with:
seen in what pt population:
- Prevalence increases with age
- Severity of disease (including advanced fibrosis/cirrhosis) increases with age
- Males > Females
- Hispanics > Caucasians > African Americans
Obesity has been increasing over the years in America leading to ______ being the most common reason for liver transplant
NAFLD
Most common liver disease in children in US
NAFLD:
increaes in prevelance with age
more common in boys
Hispanic > Asian > White > Black
***18% of these kids have NASH
•_________ rather than
hypercholesteremia increases risk for NAFLD
Hypertriglyceridemia
**• 3-fold greater risk with triglycerides >200
Causes of Steatosis and Steatohepatitis
Insulin resistance, alcohol, abetalipoproteinemia
meds: Amiodorone, steroids, HAART, Tamoxifen, Diltazem
Nutrition (TPN, Severe Starvation, refeeding syndrome)
Weigth changes; jejunoileal bypass and gastric bypass
What is the progression and development of NAFLD; starting with increased oral intake and sedentary life style
(possible genetic influence)–> become obese/HTN/Hyperlipidemia:
Lead to Insulin resistance: causing normal–> steatosis
Oxidative stress further affects liver:
steatosis –> steatohepatitis –> cirrhosis
What does a fatty liver look like on ultrasound?
On CT?
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
What do we target when treating NAFLD?
Treat insulin resistance that is from obesity/HTN/hyperlipidemia
Treat the oxidative stress
prevent pts becoming fat
How much do we recommend pts to lose to have improved symtpoms if they have NAFLD
Loss of at least 3-5% of body weight necessary
to improve steatosis but up to 10% may be
needed to improve inflammation.
2 tx for NASH and their effect on patient?
Treat NASH with Pioglitazone or Vitamen EEndpoint: improvement in histology score
(steatosis, inflammation, ballooning degeneration and fibrosis)
reduced transanimase
reduced inflammation
NEITHER reduced fibrosis
What tx to patients gain more weight on for TX of NASH
Pioglitazone
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.
biopsy-proven NASH
improves liver histology in non-diabetic patients with biopsy-proven NASH and should be considered first-line therapy
• Vitamin E at a dose of 800 IU/day
vitamin E is not
recommended to treat NASH in what three pt populations
diabetic patients, NAFLD without liver biopsy, NASH
cirrhosis or cryptogenic cirrhosis.
