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Flashcards in hepatitis and alcoholic liver disease Deck (56):
1

hepatitis ddx

cholelitiasis, choledocholithiasis
HCC

2

hepatitis workup

CBC, CNP
fractionate Hgb
lipase
US of RUQ, or entire abdomen

3

hepatitis

common features??

Inflammation of the liver
broad spectrum: Viral, toxic, metabolic, pharmacologic or immune-mediated

Common pathologic features are:
-Hepatocellular necrosis (focal or extensive)
-Inflammatory cell infiltration of the liver (Portal areas vs parenchyma)


4

Acute Hepatitis

culminates in either ??

less than 6 months
-Complete resolution of liver damage with return to normal function/structure
*OR*
-A rapid progression toward extensive necrosis and death

5

Chronic Hepatitis

longer than 6 months
-Difficult to differentiate from acute hepatitis on clinical or histologic criteria alone

6

Common Causes of acute hepatitis

Viral hepatitis (A through E)
Drugs (prescription, OTC and illicit)
Alcohol
Toxins
Autoimmune
Wilson Disease

7

What is Wilson Disease??

AR
-accumulation of copper in various tissues: Liver, brain, and corneas
-Neuropsychiatric s/s along with liver disease is present
-Diagnostic evaluation:
Low serum ceruloplasmin with high urinary and hepatic copper levels (do not need biopsy unless labs inconsistent)
-Treatment: (Indefinite) Copper chelation, Zinc supplementation
-avoid shellfish, organs, chocolate

8

mechanism of Acute Hepatitis

-Direct toxin-induced necrosis: Acetaminophen *(tylenol: daily allowance is 3g, toxic dose is 150 mg/kg, N-acetylecysteine (Mucomyst) 150 mg/kg for antidote)*, Amanita phalloides toxin (mushrooms)
-Host immune-mediated damage: Viral hepatitis

9

?? is the most common cause of hepatitis in the U.S.
?? is the 2nd most common cause
?? is the most prevalent hepatitis virus worldwide

Hepatitis A

Hepatitis B (Most extensively characterized)

Hepatitis C: infrequent cause of symptomatic acute hepatitis (more chronic), Accounts for most cases of acute hepatitis previously designated as non-A, non-B

10

Hepatitis D is an ?? virus
Requires ?? for transmission

incomplete RNA virus
HBV (HBsAg); Thus only causes hepatitis in people with HBV


11

?? is typically found in endemic areas, Most commonly associated with poor sanitation
Shares many similarities with ??

Hepatitis E

hepatitis A

12

Acute Viral Hepatitis Clinical Manifestations:

-prodromal phase (several days): typ. constitutional and GI symptoms
-5-10% of hepatitis-B and C cases will have arthritis and urticaria (like serum sickness, from immune complex deposition)
-Jaundice with bilirubinemia/bilirubinuria and acholic stools follow (typ. feel better here)
-hepatomeg (splenmeg in 20% of pts)

*Many patients are asymptomatic or have symptoms without jaundice and thus do not seek medical attention

13

acute viral hep labs

-ALT and AST are often greater than 20-fold normal and as high as 100-fold normal
-bilirubin elevation (more than 2.5 to 3 mg/dL) results in jaundice and defines icteric hepatitis
-alk phos usually limited to 3x normal (Except in cholestatic hepatitis)
-CBC usually shows mild leukopenia w. atypical lymphocytes



14

acute HBV outcomes
90%-->??
9%-->??
1%-->??

90%: resolution
9%: chronic hepatitis (HBsAg+ for >6 mos)
1%: fulminant hepatitis

15

chronic hepatitis (HBsAg+ for >6 mos)-->

50% resolution
-others:
carrier
chronic persistent or chronic active-->polyarteritis nodosum, glomerulonephritis, cirrhosis, *HCC*

16

Complications of Hepatitis

-Cholestatic hepatitis: Self-lim. w. marked conjugated hyperbili, alk phos and pruritus, Usually assoc. with hepA, evaluate for and rule-out biliary obstruction
-Fulminant hepatitis: Due to massive hepatic necrosis, Occurs in less than 1% of patients with hepatitis, Leads to fulminant hepatic failure

17

more complications of hepatitis

-Chronic hepatitis: typ. seen in hepB,C, D (1-10% in HBV (90% in neonates), 85% in HCV, Common in HDV)
-rare complications: Cryoglobulinemia (HBV and HCV)
Glomerulonephritis (HBV and HCV)
Polyarteritis nodosa (HBV)


18

All cases of hepatitis A, B and E are ??

Treatment of acute ?? is important

Antiviral therapy in ?? has not shown clear benefit

self-limited; Unless complicated by fulminant hepatitis
-hepatitis C: Early treatment (within 12 wks of diagnosis) with INF-a induces high sustained virologic response rates
-hepatitis B

19

Treatment in all other cases of hepatitis is supportive

Hospitalization may be required in those with ??

-Rest, Maintenance of hydration
-Adequate dietary intake (low-fat, high carb), Avoid alcohol
-Treat nausea/vomiting with anti emetics

-severe dehydration and/or deteriorating liver function

20

how to prevent hepatitis

Vaccination is available for: ??

Post-exposure immunoglobulin is available for: ??

-Good hygiene: preventative for all
-Proper universal precautions for preventing HepB,C
-vaccine for Hepatitis-A, B, E
HepD will be covered by the Hep-B vaccine
There is no vaccine for Hep-C
-IgG post-exp. for hepA and B, no proven benefit for HCV

21

drugs that cause heptatitis

Analgesics
Antibiotics and antivirals
Central nervous system agents
Herbs
also Statins

22

?? is the leading cause of acute liver failure in the U.S. (40-50% of all cases)

other important causes

Acetaminophen OD- Mortality rate of close to 30%

NSAIDs (brain, kidney liver), Salicylates (dose-dep hepcell injury, typ mild and reversible)

23

?? are the most frequently incriminated agents causing drug-induced liver injury due to widespread use

what specific one is the leading cause of antibiotic-related liver injury and results in cholestatic hepatitis ??

Antibiotics:
Amoxicillin-clavulanic acid (augmentin, yet use to tx cholestasis!)
-others: Nitrofurantoin, isoniazid, TMP-SMX, FQs
-HIV agents

24

2nd to abx as causing drug-induced liver injury

CNS agents: Anticonvulsants and anesthetics
-Sodium valproate, phenytoin, carbamazepine and lamotrigine
-Halothane; Newer halogenated anesthetics (isoflurane, enflurane) have a much lower incidence of hepatotoxicity

25

other causes of drug induced hepatitis: herbs

Senecio, Heliotropium, Crotalaria, and comfrey contain alkaloids that cause hepatic veno-occlusive disease
-mild hepatitis to massive necrosis and fulminant hepatitis has been associated with: Chaparral, germander, pennyroyal oil, mistletoe, valerian root, comfrey and Ma huang

26

etiology of chronic hepatitis

?? is considered the most frequent cause of chronic hepatitis in US and Western Europe

Acute viral hepatitis can lead to chronic hepatitis; Hep-C being most common
-Hep-A and E not causing chronic hepatitis

Nonalcoholic steatohepatitis (NASH)

27

several drugs such as ?? can lead to chronic hepatitis

etiologic agents difficult to ID

Methyldopa-safe in pregnancy

-Quiescent autoimmune disease
-Undetected past drug-induced injury
-NASH, Antibody-negative viral infections
-Misdiagnosed cholestatic liver injury

28

classification of chronic hepatitis
Utilizes ??
Based upon ??

-biochemical and serologic studies along with liver biopsy
etiologic agent responsible for disease
Grade of injury (#’s and location of inflammatory cells)
Stage of disease on liver biopsy: Degree, location and distortion of normal architecture by fibrosis)

29

Chronic Hepatitis-B:
Occurs in ?? of those with acute hepatitis-B

tx if hepB and pregnant ??
if not pregnant??

5-10%
High versus low replicative phase
7 drugs currently approved as single agent treatments
if pregnant:
Tenofovir (HepC as well), Telbivudine
Lemivudine (used to be first line, now too much resistance)
if not pregnant: Intecovir, Tenofovir

30

Chronic Hepatitis-C:
Develops in ?? of individuals acutely exposed to hepatitis-C
More than ?? of these patients may develop cirrhosis in about 30 years

75-80%
20%

-Six major genotypes (In US, genotype 1 most common); Determines treatment type and prognosis
-New class of agents for hep-C:
serotype 2,3: Peg INF + Ribaviran
serotype 1: Peg INF + Ribaviran + antiviral (teleprovir, boseprovir) (75% remission)

31

Autoimmune liver disease:
typically occurs in ??

in young women
-Significant hepatic inflammation, preponderance of plasma cells and fibrosis
-Presence of hypergammaglobulinemia as well as antinuclear antibody (ANA) or anti-smooth muscle antibody (Anti-SMA): This is the most common classic type or type 1 variant
-no pathognomonic features

32

AI hepatitis Diagnosis based upon ??
how tx ??

Presence of autoantibodies, hypergammaglobulinemia, typical liver histology and absence of viral hepatitis

Corticosteroids and azathioprine are main stay of treatment

33

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

34

NAFLD most commonly occurs in ppl who are ??

Overweight, diabetic and have hyperlipidemia
-About 30 million Americans have NAFLD( 1/3 have NASH, 20% of these show signs of advanced disease)

35

how to dx NAFLD ??
tx??

liver biopsy with histologic examination (most don't get: use labs, CT, MRI)
-Weight reduction and exercise are established to improve liver histology in NASH
-trials for lipid-lowering agents and drugs to improve insulin resistance

36

Alcohol abuse is a major cause of liver disease in the Western World
A patient may have features of all three entities: ??
which 2 are reversible, which one irreversible ??

Fatty Liver and Alcoholic Hepatitis (reversible)
Cirrhosis (not reversible)

37

Complex mechanism of injury by alcohol:
?? are directly hepatotoxic




Ethanol, Acetaldehyde and Nicotinamide adenine dinucleotide phosphate (NADP)

38

?? are critical in initiating and perpetuating hepatic injury and producing lesions of alcoholic hepatitis

Induction of cytochrome P-450 (CYP2E1) and cytokine pathways (tumor necrosis factor-ά)

39

Risk for hepatotoxic effects from alcohol:

Men consuming ?? grams of ethanol per day for ?? years carries substantial risk for alcoholic liver disease

40-80 grams (4-8 drinks (10g/drink) of ethanol per day for 10-15 years; 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

40

clinical features of alcoholic LIVER

-Tender hepatomegaly (incidental finding)
-Aminotransferases are mildly elevated (

41

Clinical Features of Alcoholic HEPATITIS:

-asymptomatic to extremely ill with hepatic failure
-Anorexia, N/V, weight loss and abd pain
-Hepatomegaly is present in 80% of cases, often splenmeg
-Fever is common, Jaundice is commonly present – may be prounounced
-Cutaneous signs may be found: Spider angiomas, palmar erythema, gynecomastia

42

more clinical features of Alcoholic HEPATITIS:

-Ascites and encephalopathy may be present (severe disease)
-WBC count may be markedly elevated
-Aminotransferases are only modestly increased: 200-400 U/L: An important differentiator from other acute hepatitis
*Ratio of AST to ALT nearly always exceeds 2:1*, In contrast to viral hepatitis (usually parallel increases)
-Prolonged prothrombin time (elev. INR), Hypoalbuminemia, Hyperglobulinemia

43

Alcoholic Fatty Liver/Hepatitis dx

-honest hx of prolonged etOH abuse-difficult!
-Historical, clinical and biochemical features of alcoholic hepatitis may be sufficient
-if uncertainty: Serologic testing and a liver biopsy may be necessary to establish diagnosis
-histo findings

44

Histological findings of alcoholic hepatitis include:

-Mallory bodies
-Infiltration by PMNs
-network of interlobular connective tissues surrounding hepatocytes and central veins

45

Alcoholic Fatty Liver/Hepatitis prognosis ??

complications ??

AFLD: 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) and/or Hepatic failure and death

other complications: Enceph, Ascites, Hepatorenal syndrome, GIB (varices)

46

Alcoholic Fatty Liver/Hepatitis tx

?? oral TNF-a antagonist shown to have benefit in sev. alcoholic hepatitis by decreasing risk of renal failure

-Abstinence: AFLD and early stages of alcoholic hepatitis (without extensive fibrosis) are reversible
-Supportive care: High calorie diet with vitamin and protein-supplementation
-Corticosteroids: methylprednisone if high MELD score
-Pentoxifylline

47

causes of Liver Cirrhosis
what is it??

Alcohol is one of the most common causes, next: HepC, NAFLD
-An irreversible end result of insult/injury to the liver: Fibrous tissue replaces healthy hepatocytes and liver tissue, (>25,000 deaths/yr in the U.S.)

48

Patients with cirrhosis are often ??
or may present with ??

asymptomatic: dx usually incidentally established at time of phys exam, lab testing or radiologic testing for unrelated purposes

specific complications: Variceal bleeding, Ascites, Spontaneous bacterial peritonitis and hepatic encephalopathy


49

Liver Cirrhosis: typ nonspecific hx including ??

Fatigue, weight loss, anorexia, nausea
Increased abdominal girth, abdominal discomfort

50

Liver Cirrhosis Physical exam findings include:

-Jaundice, Abnormal liver span or consistency
-Splenomegaly, Ascites, LE edema
-Spider angiomas, Palmar erythema, Gynecomastia
-Nail changes (Terry Nails, Muehrcke lines)
-Caput medusae, Asterixis, Testicular atrophy

51

Liver Cirrhosis Diagnosis:
combine Clinical, Laboratory and radiologic findings for most reliable dx

-Liver biopsy: More for staging and severity, px and response to tx (don't need to start tx)
-lab and radiologic findings

52

Liver Cirrhosis lab findings

Hypoalbuminemia, Prolongation of prothrombin time
-Hyperbilirubinemia, Low blood urea nitrogen (BUN) levels
-Elevated serum ammonia levels
-Liver enzymes will vary with etiology and stage of cirrhosis

53

Liver Cirrhosis imaging

US, CT, MRI
Relative enlargement of left hepatic and caudate lobes (right lobe atrophy), Surface modularity, Features of portal HTN (Ascites, Intraabdominal varices, splenomegaly)

54

Liver Cirrhosis Major Complications:

-Consequence of hepatocel dysfunction: Jaundice, Coagulopathy, Hypoalbuminemia
-Consequence of portal HTN: Variceal hemorrhage, Ascites, Spontaneous bacterial peritonitis Hepatorenal syndrome, Hepatic encephalopathy Hepatopulmonary syndrome
-HCC


55

hemochromotosis

AR mutation on HFE of chrom. 6
-increase absorption of Fe from duodenum
-deposits as hemosiderin on liver pancreas, heart, testes, adrenals, etc
-symptoms after age 50: gray/brown changes-->bronze
-elevations: AST, alk phos, Fe, ferritin elevations
-CT, MRI: can do quantitative hepatic iron store level

56

hemochromatosis tx and prognosis

phlebotomy until Fe stores down, add PPI to dec. Fe absorption, avoid red meat, shellfish, vit C, etOH
-chelating agent (deferoxamine) if can't handle phlebotomy
-liver fibrosis can improve with tx:
-at risk for infections w. vibrio, yersinia, listeria
-still at risk for HCC