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Internal Medicine > JH IM Board Review - Acute and Chronic Liver Disease I > Flashcards

JH IM Board Review - Acute and Chronic Liver Disease I Flashcards

1
Q

Evaluation of elevated liver tests - When to fully evaluate?

A

Persistently or markedly (more than 10 times normal for aminotransferases or more than 4 times normal for alkaline phosphatase [AP]) elevated liver tests should ALWAYS BE FULLY EVALUATED.

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2
Q

AST and ALT values can guide us how?

A

Greater than 1000 IU/mL ==> Indicative of ACUTE viral, toxic, or ischemic hep.

==> Alcoholic hep almost NEVER raises aminotransferases above 400 IU/mL.

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3
Q

Which tests are the liver function tests and what do they reflect?

A
  1. Bilirubin.
  2. PT.
  3. Albumin.

==> REFLECT SYNTHETIC CAPACITY OF THE LIVER.

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4
Q

ALBUMIN HALF-LIFE:

A

3 WEEKS.

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5
Q

Contrary to the popular term “LFTs” …?

A

Aminotransferases and AP are NOT true liver function tests.

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6
Q

Dx - Investigating elevated liver enzymes - 1st step:

A
  1. Look at PATTERN of elevation ==> Dictates the evaluation process and diseases to be considered.
  2. A careful history and a review of patient’s medications, both prescribed + OTC, are CRITICAL.
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7
Q

Dx - Investigating elevated liver enzymes - Elevated aminotransferases should first be evaluated by …?

A

Serologic and biochemical tests.

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8
Q

Dx - Investigating elevated liver enzymes - Elevated bilirubin OR AP should be evaluated by an …?

A

US of the biliary tree + Anti-mt antibody.

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9
Q

Dx - Investigating elevated liver enzymes - If ascites is present …?

A

DOPPLER studies of hepatic veins to r/o outflow obstruction of the liver.

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10
Q

Dx - Investigating elevated liver enzymes - When to liver Bx?

A

Should be considered when diagnostic confirmation in required or if serologic and biochemical tests have NOT revealed the cause of the liver enzyme abnormality.

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11
Q

Elevated AP + GGT or 5-nucleotidase - What to do next?

A
  1. US (w/ Doppler if ASCITES present) + AMA.
  2. If AMA (+) or US normal ==> LIVER Bx.
  3. If AMA (-) or US shows dilated ducts ==> MRCP +/- ERCP.
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12
Q

Elevated AST and ALT - What to do next?

A
  1. Viral serologies, ANA, SMA, Iron studies, ceruloplasmin, AAT.
  2. Bx if above not helpful or to stage disease.
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13
Q

Summary of common liver disorders - Autoimmune hep:

A
  1. Elevated AST, ALT.
  2. Dx ==> ANA, SMA, Igs.
  3. Give prednisone + aza, transplant.
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14
Q

Summary of common liver disorders - PBC:

A
  1. Elevated AP.
  2. AMA.
  3. UDCA, transplant.
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15
Q

Summary of common liver disorders - PSC:

A
  1. Elevated AP.
  2. ERCP, MRCP, pANCA.
  3. Stenting of strictures, transplant.
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16
Q

Acute liver failure (ALF) is defined as …?

A

An onset of coagulopathy (ie INR >1.5) and encephalopathy within 26 WEEKS of disease presentation + WITHOUT Hx of liver disease.

==> Jaundice is often present as well.

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17
Q

MCC of ALF in the USA and Worldwide?

A

USA ==> Acetaminophen (35-40%).

Worldwide ==> Viral hep.

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18
Q

No specific cause of ALF is identified in approx. …% of cases.

A

20%.

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19
Q

ALF presentation - Pts may present with encephalopathy, the severity of which is related to …?

A

THE PRESENCE OF CEREBRAL EDEMA.

==> Cerebral edema can result in BRAINSTEM HERNIATION ==> LEADING CAUSE OF DEATH IN ALF.

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20
Q

ALF presentation - Patients who present with jaundice and then develop encephalopathy after several days have …?

A

WORSE PROGNOSIS.

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21
Q

ALF Presentation - Other important key points:

A
  1. Often complicated by SEPSIS, MULTI-ORGAN FAILURE (renal failure, pancreatitis), GI BLEEDING, COAGULOPATHY ==> Spontaneous hemorrhage.
  2. Widespread hepatocyte necrosis leads to loss of glycogen stores and impaired gluconeogenesis, causing HYPOGLYCEMIA.
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22
Q

ALF - Prognosis can be made using which criteria?

A
  1. King’s college criteria.

2. Clichy criteria.

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23
Q

King’s college criteria - Indicators of poor prognosis in ALF - Acetaminophen toxicity:

A

Arterial pH <7.3 after adequate fluid resuscitation OR all of the following within a 24h period:

  1. PT >100 (INR >6.5).
  2. Serum Cr >3.4mg/dL.
  3. Grade 3 to 4 HE.
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24
Q

King’s college criteria - Indicators of poor prognosis in ALF - NON-acetaminophen causes of ALF:

A

PT >100sec (INR >6.5) and HE (irrespective of grade). OR ANY 3 of the following:

  1. Wilson, idiosyncratic drug reaction, seronegative, or indeterminate hepatitis.
  2. Jaundice >7days before HE.
  3. Age <10 OR >40.
  4. PT >50 (INR >3.5).
  5. Bilirubin >17mg/dL.
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25
Q

ALF - Tx - Monitor which parameters?

A
  1. PT.
  2. pH.
  3. Glucose.
  4. Liver enzymes.
  5. Cultures.
  6. Fluid and electrolytes balance + CVP.
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26
Q

ALF - Tx - What to give?

A
  1. Enteral feeding, dextrose infusion, thiamine.
  2. PPI or H2 antagonists.
  3. N-acetylcysteine for ALL causes.
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27
Q

ALF - Tx - Mechanical ventilation?

A

To protect airways in pts with delirium.

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28
Q

ALF - Tx - Other important actions to take?

A
  1. Elevate head of bed.
  2. Hyperventilate initially.
  3. Induce hypothermia.
  4. Administer mannitol if serum osmolarity is less than 320 mOsm to keep ICP low; avoid procedures that may elevate the ICP.
  5. ICP monitor, when available, should be used to monitor perfusion pressures and ICP.
  6. Continuous venovenous hemofiltration for renal failure.
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29
Q

ALF - Tx - Clotting factors:

A

Incl. recombinant VII ==> ONLY FOR ACTIVE BLEEDING or before invasive procedures.

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30
Q

ALF - Tx - Disease-specific Tx?

A
  1. Penicillin G and silibinin for Amanita poisoning.
  2. Acyclovir for herpes hep.

==> There is some evidence that supports empiric use of acyclovir in idiopathic cases.

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31
Q

ALF - Tx - Transplantation:

A

Early transfer to liver transplantation center results in improved survival.

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32
Q

Drug-induced liver injury (DILI):

A
  1. MCC of ALF (>50%) in the USA.
  2. 6% of all adverse reactions involve the liver.
  3. DILI is the MC REASON for postmarketing withdrawal of medications.
  4. Reactions can be dose-dependent OR idiosyncratic.
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33
Q

DILI - Symptoms:

A

Range from ASYMPTOMATIC to nonspecific complaints, such as fatigue, nausea, vomiting, and/or mild RUQ pain.

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34
Q

DILI - Can follow several patterns of injury:

A
  1. Hepatitis.
  2. Cholestasis.
  3. Mixed cholestatic hep.
  4. Progressive bile duct injury ==> VANISHING BILE DUCT SYNDROME.

==> Injury pattern can give clue to offending agent.

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35
Q

Hepatic injury caused by various medications - Nonspecific or viral-like hep?

A
  1. Aspirin.
  2. Amiodarone.
  3. Diclofenac.
  4. INH.
  5. Methyldopa.
  6. Nitrofurantoin.
  7. Phenytoin.
  8. PTU.
  9. Sulfonamides.
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36
Q

Hepatic injury caused by various medications - Cholestasis:

A
  1. Carbamazepine.
  2. Chlorpromazine.
  3. Cotrimoxazole.
  4. Haloperidol.
  5. TCAs.
  6. Estrogens.
  7. 17-alpha steroids.
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37
Q

Hepatic injury caused by various medications - Steatosis:

A
  1. Alcohol.
  2. Prednisone.
  3. Tetracycline.
  4. Valproic acid.
  5. Amiodarone.
  6. Zidovudine.
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38
Q

Hepatic injury caused by various medications - Granulomatous hepatitis:

A
  1. Allopurinol.
  2. Quinidine.
  3. Sulfonamides.
  4. Sulfonylureas.
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39
Q

Hepatic injury caused by various medications - Veno-occlusive disease:

A
  1. Antineoplastics.
  2. Azathioprine.
  3. Pyrrolizidine alkaloids.
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40
Q

Hepatic injury caused by various medications - Adenomas and HCC:

A

Estrogens and anabolic steroids.

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41
Q

DILI - Other key features to keep in mind:

A
  1. Some cases can be immune-mediated, and HYPEREOSINOPHILIA is present (both in serum and on liver biopsy).
  2. Most biochem parameters return to normal after eliminating the offending agent.
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42
Q

DILI - Dx:

A
  1. Dx OF EXCLUSION: First exclude other more common causes of liver disease.
  2. Rechallenging with the suspected drug is NOT recommended.
    ==> If the liver injury is immune-mediated, 2nd exposure may be more severe than the initial episode.
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43
Q

Liver monitoring schedule for hepatotoxic medications - Every month?

A
  1. Azathioprine.
  2. All azoles (eg fluconazole).
  3. Protease inhibitors.
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44
Q

Liver monitoring schedule for hepatotoxic medications - Every month for 3 months, then every 3 months?

A
  1. Niacin.

2. Tacrine.

45
Q

Liver monitoring schedule for hepatotoxic medications - Every 3 months?

A
  1. Amiodarone.
  2. Antiepileptics.
  3. Diclofenac.
  4. Statins.
  5. Herbal remedies.
  6. NSAIDs (other) ==> 3-6months.
46
Q

Autoimmune hep (AIH) should be considered when?

A

Aminotransferases are elevated, the patient has negative viral serologies, and no drug injury is implicated.

47
Q

2 types of AIH:

A
  1. BOTH more common in WOMEN.

2. Distinction between subtypes is NOT particularly useful with respect to management.

48
Q

Type 1 AIH:

A

80%.

==> Peak incidence between 16-30.

==> More than 20% of pts are >60yr.

49
Q

Type 2 AIH:

A

20%.

==> Typically presents ACUTELY IN CHILDHOOD.

50
Q

AIH - Concommitant autoimmune diseases:

A
  1. Thyroiditis.
  2. Type I DM.
  3. SLE.
  4. Sjogren syndrome.
51
Q

AIH - Dx:

A
  1. Elevated liver enzymes with negative viral hep serologies + Elevated gamma globulin (esp. IgG).
  2. Supported by histology of interface hep, plasma cells, portal tract inflammation.
  3. Autoantibodies NOT invariably present.
52
Q

Serologic features of AIH variants - Type 1 (classic):

A
  1. SMA +/-.
  2. ANA +/-.
  3. Anti-F actin +/-.
  4. Antisoluble liver antigen/ Liver pancreas antigen +/-.
53
Q

Serologic features of AIH variants - Type 2:

A
  1. Anti-liver kidney microsomal type 1 ab +.

2. Anti-liver cytosol 1 +/-.

54
Q

AIH - Tx indications:

A
  1. Aminotrans 10 times normal.
  2. Aminotrans 5 times normal + 2 times up gamma globulin.
  3. Significant inflammation +/- necrosis on liver biopsy.

==> Many clinicians treat AIH before the aminotrans reach this degree of elevation.

55
Q

AIH - Initial Tx:

A

Prednisone +/- aza for at least 18 to 36 months (majority of pts require lifelong Tx).

56
Q

AIH - Tx for pts not responsive to standard regimen:

A

May require more potent immunosuppressives ==> Mycophenolate mofetil, cyclosporine, or tacrolimus.

57
Q

AIH - After cessation of Tx …?

A

80% of pts in remission, eventually RELAPSE.

==> 50% within 6 months.

58
Q

AIH - Liver tranplantation for …?

A

Decompensated cirrhosis.

59
Q

AIH - After transplantation?

A

30% recurrence rate, with an average time to recurrence of 5 years.

60
Q

PBC - Disease of the small or large bile ducts?

A

SMALL bile ducts.

61
Q

PBC - 1st degree relatives have how higher risk?

A

50-100-fold higher relative risk compared to general population.

62
Q

PBC - Age?

A

Median = 50yrs.

Broad range ==> 20-90.

63
Q

PBC - Women or men?

A

90% are women.

64
Q

PBC - Long-term survival?

A

Excellent in those responding to treatment in the 1st year of Tx (70% survival after 20years).

65
Q

PBC - How is response to Tx measured?

A

By fall in AP to within 1.67x upper limit of normal.

66
Q

PBC - Elevated total cholesterol?

A

UNCLEAR effect on CV risk.

==> Mostly HDL. Classic dogma is no increased risk, but this has recently been challenged.

67
Q

PBC - Dx:

A

95% HAVE AMA.

==> Less than 1% of healthy population has AMA.

==> ANA also in most cases.

68
Q

PBC - Tx:

A

UDCA 13-15mg/kg/day.

  1. Improves transplant-free survival.
  2. Improves liver chemistries.
  3. Slows histological progression.
69
Q

UDCA - Exact mechanism is unclear:

A

Possibly:

  1. Incr. canalicular excretion of toxic bile acids.
  2. Inhibits intestinal bile acid reabsorption.
  3. Scavenges ROS.
70
Q

Should be UDCA stopped at some time?

A

NEVER. Continued indefinitely.

71
Q

PBC - What to give for pruritus?

A

Bile acid sequestrants (cholestyramine/colestipol) for pruritus.

==> 2nd line ==> Rifampin, opioid antagonists, SSRIs.

72
Q

PBC - Transplantation:

A

Should be considered once cirrhosis and jaundice develop.

==> 5yr post-transplant survival is 80% (among the highest for all liver diseases.

==> Recurrence rate POST-transplantation is 20-25%.

73
Q

PSC is a disease of …?

A

MEDIUM and LARGE bile ducts.

74
Q

PSC - Median age:

A

40.

75
Q

PSC - Most cases (80%) are associated with …?

A

IBD (particularly UC).

76
Q

PSC - What percentage of pts with UC have PSC?

A

2.5%-7.5%.

77
Q

UC + PSC and CRC?

A

INCREASED RISK OF COLON CANCER IN PTS WITH UC AND PSC.

78
Q

What percentage of PSC pts have Crohn?

A

10-15%.

79
Q

PSC and cholangiocarcinoma?

A

10y cumulative incidence is 7-9%.

80
Q

PSC - Median survival?

A

9.5-12 YEARS from diagnosis to death or liver transplantation.

81
Q

PSC - Small or large duct PSC has better prognosis?

A

SMALL.

82
Q

PSC - Diagnosis:

A

Made by ERCP and MRCP ==> demonstrates strictures or beading of the intrahepatic or extrahepatic bile ducts.

83
Q

PSC - Gold standard for Dx:

A

ERCP. (But invasive)

84
Q

PSC - Dx - MRCP:

A

Sens ==> 80% or more.

Spec ==> 87% or more.

85
Q

PSC - Role of liver Bx in Dx:

A

Classically shows periductal concentric fibrosis (“onion skin”) but is often nondiagnostic, especially in early disease.

  1. Not essential for the Dx of PSC.
  2. Can be helpful in assessing possible overlap syndromes and liver fibrosis.
86
Q

PSC - Tx - UDCA:

A
  1. Low dose (13-15mg/kg/day) may improve biochem tests but does NOT alter symptoms, progression to cirrhosis, or survival.
  2. Some experts advocate for the use of low-dose UDCA if there is a reduction in AP after 6 to 12 months of use.
  3. High-dose (28-30mg/kg/day) UDCA may be associated with increased serious adverse events and is NOT recommended.
87
Q

PSC - Screening for:

A
  1. IF CONCOMMITANT COLITIS ==> Annual screening for CRC.

2. ANNUAL screening for gallbladder mass lesions and cholangiocarcinoma with serum CA 19-9 and MRI/MRC.

88
Q

PSC - Liver transplantation:

A

Should be offered to those with advanced liver disease or repeated bouts of cholangitis.

89
Q

PSC - Recurrence after transplant:

A

20-25% of pts 5-10 yr after transplantation.

90
Q

Alcoholic liver disease (ALD) - How much drink?

A

> 60g/day ==>HEAVY drinkers.

==> 10-35% of heavy drinkers develop ALD.

91
Q

Cirrhosis develops in how many heavy drinkers?

A

8-20%.

92
Q

ALD - Variables contributing to higher likelihood of ALD:

A
  1. Incr. quantity of ingested alcohol.
  2. Malnutrition.
  3. Female gender.
  4. Concommitant HCV.
93
Q

Alcoholic cirrhosis - Prognosis:

A

WORSE than other causes of cirrhosis.

==> HRS is a frequent cause of death.

94
Q

Patient with ALD may have CO-EXISTING:

A
  1. CARDIOMYOPATHY.
  2. Pancreatic insufficiency.
  3. +/- neurotoxicity.
95
Q

ALD - Serum Igs?

A

IgA is often ELEVATED.

96
Q

ALD - Role of liver Bx:

A

Can be used to stage fibrosis + exclude other forms of liver disease.

97
Q

ALD - Histopathology:

A

Varies depending on the nature of injury:

  1. Macrovesicular steatosis.
  2. Lobular inflammation.
  3. Ballooning degeneration (in alcoholic hepatitis).
  4. Parenchymal necrosis (in alcoholic hepatitis).
  5. Periportal fibrosis, or cirrhosis.
  6. Mallory bodies are a classic finding on Bx, but are NOT specific for ALD.
98
Q

ALD - Tx - Most critical component of Tx:

A

ABSTINENCE.

99
Q

ALD - Tx - How to reduce alc craving and consumption?

A

BACLOFEN given orally 5mg 3 times a day for 3 days followed by 10mg 3 times a day can reduce alcohol craving and consumption.

100
Q

ALD - Tx - Reversal of portal HTN?

A

Possible after prolonged abstinence.

101
Q

ALD - Tx - Nutrition?

A

IMPORTANT.

==> Nutritional intervention may be at least as efficacious as corticosteroid therapy in the Tx of acute alcoholic hep.

102
Q

ALD - Tx - Steroids:

A

PREDNISOLONE 40mg/day for 4 weeks +/- taper over 2 to 4 weeks may offer MODEST benefit in improving short-term survival in acute alcoholic hep.

103
Q

The discriminant function (DF)= …?

A

4.6 x [PT - control (in seconds)] + Serum bilirubin (in mg per deciliter) determines the severity of disease.

104
Q

DF scores of …?

A

32 or GREATER predict 30-50% mortality at 1 month.

==> This signals the need to consider medical therapy.

105
Q

Long-term survival benefits of corticosteroids in acute alcoholic hep have …?

A

NOT BEEN SHOWN.

106
Q

ALD - Tx - Role of pentoxifylline:

A

400mg 3times daily for 4 weeks may improve short-term survival in acute alcoholic hep by decreasing the risk of HRS.

107
Q

ALD - Tx - When to consider pentoxifylline?

A

When DF score 32 or greater if steroids are CONTRAINDICATED (eg active infection).

108
Q

Pentoxifylline is …?

A

A PDE inhibitor ==> ALSO reduces the production of inflammatory cytokines such as TNF-alpha, IL-5, 10, 12.

Internal Medicine (106 decks)

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