hepatitis and alcoholic liver disease Flashcards

1
Q

hepatitis ddx

A

cholelitiasis, choledocholithiasis

HCC

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2
Q

hepatitis workup

A

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

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3
Q

hepatitis

common features??

A

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)
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4
Q

Acute Hepatitis

culminates in either ??

A

less than 6 months

  • Complete resolution of liver damage with return to normal function/structure
  • OR*
  • A rapid progression toward extensive necrosis and death
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5
Q

Chronic Hepatitis

A

longer than 6 months

-Difficult to differentiate from acute hepatitis on clinical or histologic criteria alone

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6
Q

Common Causes of acute hepatitis

A
Viral hepatitis (A through E)
Drugs (prescription, OTC and illicit)
Alcohol
Toxins
Autoimmune
Wilson Disease
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7
Q

What is Wilson Disease??

A

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

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8
Q

mechanism of Acute Hepatitis

A
  • 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
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9
Q

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

A

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

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10
Q

Hepatitis D is an ?? virus

Requires ?? for transmission

A

incomplete RNA virus

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

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11
Q

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

A

Hepatitis E

hepatitis A

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12
Q

Acute Viral Hepatitis Clinical Manifestations:

A
  • 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

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13
Q

acute viral hep labs

A
  • 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
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14
Q

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

A

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

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15
Q

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

A

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

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16
Q

Complications of Hepatitis

A
  • 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
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17
Q

more complications of hepatitis

A

-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)

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18
Q

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

Treatment of acute ?? is important

Antiviral therapy in ?? has not shown clear benefit

A

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
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19
Q

Treatment in all other cases of hepatitis is supportive

Hospitalization may be required in those with ??

A
  • 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

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20
Q

how to prevent hepatitis

Vaccination is available for: ??

Post-exposure immunoglobulin is available for: ??

A

-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

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21
Q

drugs that cause heptatitis

A
Analgesics
Antibiotics and antivirals
Central nervous system agents
Herbs
also Statins
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22
Q

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

other important causes

A

Acetaminophen OD- Mortality rate of close to 30%

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

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23
Q

?? 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 ??

A

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

24
Q

2nd to abx as causing drug-induced liver injury

A

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
Q

other causes of drug induced hepatitis: herbs

A

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
Q

etiology of chronic hepatitis

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

A

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
Q

several drugs such as ?? can lead to chronic hepatitis

etiologic agents difficult to ID

A

Methyldopa-safe in pregnancy

  • Quiescent autoimmune disease
  • Undetected past drug-induced injury
  • NASH, Antibody-negative viral infections
  • Misdiagnosed cholestatic liver injury
28
Q

classification of chronic hepatitis
Utilizes ??
Based upon ??

A

-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
Q

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

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

A

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
Q

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

A

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
Q

Autoimmune liver disease:

typically occurs in ??

A

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
Q

AI hepatitis Diagnosis based upon ??

how tx ??

A

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

Corticosteroids and azathioprine are main stay of treatment

33
Q

Nonalcoholic Fatty Liver Disease encompasses ??

A

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
Q

NAFLD most commonly occurs in ppl who are ??

A

Overweight, diabetic and have hyperlipidemia

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

35
Q

how to dx NAFLD ??

tx??

A

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
Q

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 ??

A

Fatty Liver and Alcoholic Hepatitis (reversible)

Cirrhosis (not reversible)

37
Q

Complex mechanism of injury by alcohol:

?? are directly hepatotoxic

A

Ethanol, Acetaldehyde and Nicotinamide adenine dinucleotide phosphate (NADP)

38
Q

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

A

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

39
Q

Risk for hepatotoxic effects from alcohol:

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

A

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
Q

clinical features of alcoholic LIVER

A
  • Tender hepatomegaly (incidental finding)

- Aminotransferases are mildly elevated (

41
Q

Clinical Features of Alcoholic HEPATITIS:

A
  • 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
Q

more clinical features of Alcoholic HEPATITIS:

A
  • 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
Q

Alcoholic Fatty Liver/Hepatitis dx

A
  • 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
Q

Histological findings of alcoholic hepatitis include:

A
  • Mallory bodies
  • Infiltration by PMNs
  • network of interlobular connective tissues surrounding hepatocytes and central veins
45
Q

Alcoholic Fatty Liver/Hepatitis prognosis ??

complications ??

A

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
Q

Alcoholic Fatty Liver/Hepatitis tx

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

A
  • 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
Q

causes of Liver Cirrhosis

what is it??

A

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
Q

Patients with cirrhosis are often ??

or may present with ??

A

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
Q

Liver Cirrhosis: typ nonspecific hx including ??

A

Fatigue, weight loss, anorexia, nausea

Increased abdominal girth, abdominal discomfort

50
Q

Liver Cirrhosis Physical exam findings include:

A
  • 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
Q

Liver Cirrhosis Diagnosis:

combine Clinical, Laboratory and radiologic findings for most reliable dx

A
  • Liver biopsy: More for staging and severity, px and response to tx (don’t need to start tx)
  • lab and radiologic findings
52
Q

Liver Cirrhosis lab findings

A

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
Q

Liver Cirrhosis imaging

A

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
Q

Liver Cirrhosis Major Complications:

A
  • 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
Q

hemochromotosis

A

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
Q

hemochromatosis tx and prognosis

A

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