Hepatitis/Alcoholic Liver Disease Flashcards
Pathological features of hepatitis
- inflammation of the liver
- Hepatocellular necrosis (focal or extensive)
- Inflammatory cell infiltration of the liver (Portal areas vs parenchyma)
Acute hepatitis
-condition lasting less than 6 months
1. Complete resolution of liver damage with return to normal function and structure
OR
2. Rapid progression of the acute injury toward extensive necrosis and a fatal outcome
Chronic hepatitis
- sustained inflammatory process lasting longer than 6 months
- Difficult to differentiate from acute hepatitis on clinical or histologic criteria alone
Common causes of acute hepatitis
- Viral hepatitis (A through E)
- Drugs (prescription, OTC and illicit)
- Alcohol
- Toxins
- Autoimmune
- Wilson Disease
Wilson Disease
- Autosomal recessive disorder
- Results in accumulation of copper in various tissues (liver, brain, and corneas)
-Neuropsychiatric s/s along with liver disease is present
How to diagnose Wilson Disease
Low serum ceruloplasmin with high urinary and hepatic copper levels
Treatment for Wilson Disease
- Indefinite
- Copper chelation
- Zinc supplementation
Acute hepatitis can be caused by direct toxin induced necrosis via
Acetaminophen or Amanita phalloides toxin (fungus/mushroom)
Acute hepatitis can be caused my host immune-mediated damage
-viral
Hep A, B, C, D, E viruses
Most common cause of acute hepatitis in the US?
Hep A virus
-Hep B is 2nd most common
Most extensively characterized
Most prevalent hepatitis virus world wide?
Hep C
- But is an infrequent cause of symptomatic acute hepatitis
- Accounts for most cases of acute hepatitis previously designated as non-A, non-B
Hep B antigens
HBsAg (surface)
HBeAg (Be Ag)
HBcAg (core)
Hep Be Ag is found….
Hepatitis Be antigen (HBeAg) is found in the EARLY phase of hepatitis B infection, then a bit later the hepatitis Bs antigen becomes detectable
-Serum levels of both antigens rise rapidly during the period of viral replication.
In HBV carriers and patients with chronic hepatitis B, positive HBeAg results usually indicate
presence of ACTIVE HBV replication and high infectivity
In HBV carriers and pts with chronic hep B, a negative HBeAg result indicates
very minimal or lack of HBV replication
What type of virus is Hep D?
- Hepatitis D is an incomplete RNA virus
- Requires HBV (HBsAg) for transmission**
- Thus only causes hepatitis in people with HBV
Hepatitis E is typically found in endemic areas and is most commonly associated with __________
poor sanitation
-Shares many similarities with hepatitis A
SEE SCREEN SHOT OF COMPARISON CHART
of all hepatitis viruses
Acute viral hepatitis usually starts with
- a prodromal phase (several days)
- Typically constitutional and GI symptoms
- Jaundice with bilirubinuria and acholic stools follow (pts usually feel better by now)
- Hepatomegaly is present
- Splenomegaly is present in 20% of patients
Many patients are asymptomatic or have symptoms without jaundice and thus do not seek medical attention
5-10% of hepatitis-B and C cases will have _________
- arthritis and urticaria
- Resembling serum sickness (due to immune complex deposition)
Labs with acute hepatitis
-Aminotransferases (ALT and AST) are often greater than 20-fold normal and as high as 100-fold normal
-Elevation in bilirubin (>2.5 to 3 mg/dL) results in jaundice and defines icteric hepatitis
-Alkaline Phosphatase is usually 3xs normal
(except in cholestatic hepatitis)
-CBC usually shows mild leukopenia (w/ atypical lymphocytes)
+ HepBcAb IgG means
+HepBsAb means
pt had been infected with HBV
pt has mounted an immune response to the virus and is now immune
Serology for acute hepatitis B infection
+ HBsAg
- HBsAb
+ HBcAb IgM
Serology for chronic carriers of hep B
+ HBcAb IgG
- HBcAb IgM
+ HBsAg (+ HBeAg)
-HBsAb
Chronic active: HBeAg
Chronic passive: HBeAb
Serology of people vaccinated against hep B
+ HBsAb only
(Vaccine ONLY contains HBsAg)
-no core Abs and no Ags present (the only way to get these is to be exposed to the actual virus)
Serology for window period of Hep B infection
-Window period is the time when HBsAg has disappeared, but HBsAb isn’t detectable yet
+ for HBcAb ONLY
Cholestatic hepatitis
- Self-limited with marked conjugated hyperbilirubinemia, alkaline phosphatase and pruritus
- Usually associated with hepatitis A
- Usually associated with hepatitis-A
Fulminant hepatitis
- Due to massive hepatic necrosis
- Occurs in
Chronic hepatitis is typically seen in (which types)
hepatitis B, C and D
- 1-10% in HBV (90% in neonates)
- 85% in HCV
- Common in HDV
Rare complications
with HBV and HCV
- Cryoglobulinemia (HBV and HCV)
- Glomerulonephritis (HBV and HCV)
- Polyarteritis nodosa (HBV)
Treatment for Hep A, B, E
All cases of hepatitis A, B and E are self-limited
-Unless complicated by fulminant hepatitis
-Antiviral therapy in hepatitis B has not shown clear benefit
Treatment for Hep C
Early treatment (within 12 wks of diagnosis) with interferon-alpha induces high sustained virologic response rates
Treatment in all other cases of hepatitis
- Supportive
- Rest
- Maintenance of hydration
- Adequate dietary intake (low-fat, high carb)
- Avoid alcohol
- Treat nausea/vomiting with antiemetics
- Hospitalization may be required in those with severe dehydration and/or deteriorating liver function
Prevention of hepatitis
- Good hygiene is preventative for all cases
- Proper universal precautions for preventing Hepatitis B and C
Vaccination available for
- Hepatitis-A, Hepatitis-B and Hepatitis-E
- Hepatitis-D will be covered by the Hepatitis-B vaccine
**There is no vaccine for Hepatitis-C
Post-exposure immunoglobulin is available for
- Hep A and Hep B
- No proven benefit for Hep C
There are several important classes of drugs that cause hepatitis
- Analgesics
- Antibiotics and antivirals
- Central nervous system agents
- Herbs
Leading cause of acute liver failure in US
Acetaminophen overdose
-Mortality rate of close to 30%
Analgesics that cause drug/toxin induced hepatitis
- Acetaminophen
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Salicylates (aspirin) cause dose-dependent hepatocellular injury; usually mild and easily reversible
Antibiotics/Antivirals that induce hepatitis
- Antibiotics are the most frequently incriminated agents causing drug-induced liver injury due to widespread use
- *Amoxicillin-clavulanic acid is the leading cause of antibiotic-related liver injury and results in cholestatic hepatitis**
- Nitrofurantoin, isoniazid, trimethoprim-sulfamethoxazole
- Fluoroquinolones
- HIV treatment agents have been linked to hepatic injury
CNS agents that cause hepatitis
-Second only to antimicrobials as a frequent cause of drug-induced liver injury
-Anticonvulsants and anesthetics are two important categories
(Sodium valproate, phenytoin, carbamazepine and lamotrigine)
-Halothane was implicated in liver injury/insult
(Newer halogenated anesthetics like isoflurane and enflurane have a much lower incidence of hepatotoxicity)
Herbs that are hepatotoxic
-Senecio, Heliotropium, Crotalaria, and comfrey contain alkaloids that cause hepatic veno-occlusive disease
-Hepatotoxicity ranging from mild hepatitis to massive necrosis and fulminant hepatitis has been associated with:
Chaparral, germander, pennyroyal oil, mistletoe, valerian root, comfrey and Ma huang
Chronic hepatitis
- A hepatic inflammatory process that does not resolve after 6 months
- Those with acute viral hepatitis and persistence of serum viral antigens and nucleic acids (beyond a similar period)
Most common acute viral hepatitis to lead to chronic hepatitis
hep C
hep A and E do NOT CAUSE chronic hepatitis
______ is considered the most frequent cause of chronic hepatitis in US and Western Europe.
Nonalcoholic steatohepatitis (NASH)
Drug that can lead to chronic hepatitis
Methyldopa
Chronic Hep B
- Occurs in 5-10% of those with acute hepatitis-B
- High versus low replicative phase
- 7 drugs currently approved as single agent treatments
Chronic Hep C
- Develops in 75-80% of individuals acutely exposed to hepatitis-C
- More than 20% of these patients may develop cirrhosis in about 30 years
- Six major genotypes (In US, genotype 1 most common)
- Determines treatment type and prognosis
- New class of agents for hepatitis-C
Autoimmune liver disease
- Occurs typically in young women
- Significant hepatic inflammation, high numbers of plasma cells and fibrosis
Serology for autoimmune liver disease
- Presence of hypergammaglobulinemia
- antinuclear antibody (ANA) or anti-smooth muscle antibody (Anti-SMA)
-This is the most common classic type or type 1 variant
Treatment for autoimmune liver disease
Corticosteroids and azathioprine are main stay of treatment
Nonalcoholic Fatty Liver Disease encompasses
- Steatosis (fatty liver)
- Nonalcoholic steatohepatitis (NASH)
- Cirrhosis (secondary to NASH)
-Most common reason for abnormal liver function tests among adults in the US and Western Europe
Nonalcoholic Fatty Liver Disease occurs in
Overweight, diabetic and have hyperlipidemia
1/3 of america, 30 million people
Diagnosing NAFLD
Most accurate means of diagnosis = liver biopsy with histologic examination
Treatment of NAFLD
- Weight reduction and exercise are established to improve liver histology in NASH.
- Trials looking at lipid-lowering agents and drugs to improve insulin resistance are ongoing
- Efficacy and safety have not been established at this time
Alcohol abuse leads to
Alcoholic Fatty Liver and Alcoholic Hepatitis (reversible)
Cirrhosis is not reversible
MOI of alcohol
-Ethanol, Acetaldehyde and Nicotinamide adenine dinucleotide phosphate (NADP) are directly hepatotoxic
- Induction of cytochrome P-450 (CYP2E1) and cytokine pathways (tumor necrosis factor-ά) are critical in initiating and perpetuating hepatic injury
- And producing lesions of alcoholic hepatitis
Risk for hepatotoxic effects from alcohol:
- Men consuming 40-80 grams of ethanol per day for 10-15 years carries substantial risk for alcoholic liver disease
- Women appear to have a lower threshold of injury
- Malnutrition and presence of other forms of chronic liver disease may potentiate toxic effects of alcohol in liver
Clinical Features of Alcoholic Liver Disease:
- Tender hepatomegaly (incidental finding)
- Aminotransferases are mildly elevated (
Clinical features of Alcoholic HEPATITIS
- Range from being asymptomatic to extremely ill with hepatic failure
- Anorexia, nausea, vomiting, weight loss and abdominal pain are common symptoms
- Hepatomegaly is present in 80% of cases
- Splenomegaly is often present
- Fever is common
- Jaundice is commonly present – may be prounounced
- Cutaneous signs may be found: Spider angiomas, palmar erythema, gynecomastia
- Ascites and encephalopathy may be present (severe disease)
Labs during Alcoholic HEPATITIS
-White blood cell count may be markedly elevated (PMNs)
-Aminotransferases are only modestly increased (AST>ALT): 200-400 U/L – An important differentiator from other acute hepatitis
Ratio of AST to ALT nearly always exceeds 2:1
- Prolonged prothrombin time
- Hypoalbuminemia
- Hyperglobulinemia
- Bilirubin may be markedly increased
Histological findings of alcoholic hepatitis include
- Mallory bodies
- Infiltration by polymorphonuclear leukocytes
- A network of interlobular connective tissues surrounding hepatocytes and central veins
Prognosis of Alcoholic fatty liver disease
completely resolves with cessation of alcohol intake
Alcoholic hepatitis can also resolve, but more commonly ______
it progresses:
- Cirrhosis (may be present at initial time of diagnosis)
- Hepatic failure and death
-Encephalopathy, Ascites, Hepatorenal syndrome Gastrointestinal bleeding (from varices)
Treatment
- Abstinence – Fatty liver and early stages of alcoholic hepatitis (without extensive fibrosis) are reversible.
- Supportive care – High calorie diet with vitamin and protein-supplementation is crucial
- Corticosteroids
What has been shown to benefit sever alcoholic hepatitis?
Pentoxifylline- diminishes risk for renal failure
An oral TNF-ά antagonist
Liver Cirrhosis
-From alcohol, Hepatitis-C, Nonalcoholic Fatty Liver Disease
- Fibrous tissue replaces healthy hepatocytes and liver tissue
- An irreversible end result of insult and injury to the liver
Many patients with cirrhosis are asymptomatic but some have
Variceal bleeding, Ascites, Spontaneous bacterial peritonitis and hepatic encephalopathy
Other S/S of cirrhosis
-Fatigue, weight loss, anorexia, nausea
Increased abdominal girth, abdominal discomfort
-Jaundice, Abnormal liver span or consistency
-Splenomegaly, Ascites
-Lower extremity edema
-Spider angiomas, Palmar erythema, Gynecomastia
-Nail changes (Terry Nails, Muehrcke lines)
-Caput medusae
-Asterixis
-Testicular atrophy
Findings of cirrhosis in CT/ultrasound/MRI
- Relative enlargement of left hepatic and caudate lobes (right lobe atrophy)
- Surface nodularity
- Features of portal hypertension (Ascites, Intraabdominal varices, splenomegaly)
