JH IM Board Review - Acute and Chronic Liver Disease II Flashcards
1
Q
MC liver disorder causing elevated liver enzymes in the USA?
A
NAFLD.
2
Q
NAFLD - Prevalence:
A
40%, depending on definition used and population studied.
3
Q
NAFLD - Epidemiology and race:
A
1/3 of cases of chronic liver disease in the primary care setting.
==> HISPANICS HIGH, AFRICAN AMERICANS LOW.
4
Q
NAFLD - Leading cause of death:
A
Cardiovascular disease.
5
Q
How many pts with NASH eventually progress to cirrhosis?
A
15-20%.
6
Q
MAIN risk factor for NAFLD:
A
Metabolic syndrome ==> Mainly, OBESITY + DM.
==> Insulin resistance is a hallmark.
7
Q
NAFLD - AST and ALT:
A
Usually AST/ALT <1, UNLESS ADVANCED FIBROSIS OR CIRRHOSIS ==> Then AST/ALT >1.
8
Q
NAFLD - Hepatomegaly caused by …?
A
Steatosis.
9
Q
NAFLD - How to Dx:
A
LIVER BIOPSY = GOLD STANDARD.
==> Reveals either steatosis or steatonecrosis +/- fibrosis.
==> In advanced stages, histology loses characteristic fatty infiltration and may be called “cryptogenic” cirrhosis.
10
Q
NALFD - Tx:
A
- Weight loss, strict glucose control, Tx of HTN, and lipid management are recommended.
- Vitamin E (800 IU/day) ==> Improves liver histology in biopsy-proven NASH. Unknown effects in pts with DM or cirrhosis.
11
Q
NAFLD - Insulin sensitizers and lipid-lowering agents?
A
NOT CONCLUSIVELY SHOWN BENEFIT.
12
Q
NAFLD - Liver transplantation:
A
Prognosis is worse in:
- Pts aged 60 or older.
- BMI 30 or greater.
- DM.
==> Recurrence of NAFLD and NASH after transplantation is well-described.
13
Q
Hereditary hemochromatosis (HH) - Genetics:
A
- C282Y homozygotes ==> 85-90%.
- H63D homozygotes.
- C282Y/H63D compound heterozygotes.
==> Numerous other mutations eg S65C, G93R.
14
Q
HH - Pathogenesis:
A
Incr. intestinal iron ABSORPTION:
==> Possibly caused by decr. production of the hepatic hormone HEPCIDIN, resulting in hepatic accumulation of iron.
15
Q
HH - NON-HFE-related HH include mutations of:
A
- Hemojuvelin (HJV) gene.
- Hepcidin (HAMP) gene.
- Transferrin receptor 2 (TfR2) gene.
==> AFRICAN IRON OVERLOAD (Bantu siderosis) is a non-HFE-related HH that is worsened by dietary iron loading.
16
Q
HH more common in men or women?
A
10X more common in men.
17
Q
HH - Hepatomegaly when?
A
EARLY in the disease.
18
Q
HH - HCC risk?
A
SIGNIFICANT once cirrhosis develops.
==> 5%/y.
19
Q
HH - Dx - Which clues should prompt HFE mutation analysis?
A
- Transferrin saturation >45%.
- Elevated FERRITIN in high-risk groups.
==> Gene analysis to detect C282Y or H63D mutations.
20
Q
HH - Dx - What is the next step if compound heterozygote (C282Y/H63D), C282Y heterozygote, or non-C282Y is found?
A
Need to r/o CONCOMITANT liver or hematologic conditions that may lead to 2o iron overload.
- LIVER ==> HCV, HBV, ALD, NAFLD.
- HEMATOLOGIC ==> Thal major, frequent blood transfusions, chronic hemodialysis.
21
Q
HH - Dx - Liver Bx:
A
When:
- Ferritin >1000μg/L.
- Elevated liver enzymes.
==> To stage degree of fibrosis or cirrhosis, or when not C282Y homozygote to r/o other liver diseases.
22
Q
HH - Dx - Screen 1st-degree members:
A
Either via serum transferrin saturation and ferritin.
==> Or by genetic testing.
23
Q
HH - Tx - Phlebotomy:
A
1 unit WEEKLY or BIWEEKLY (as tolerated) until goal serum ferritin of 50 to 100μg/L, followed by maintenance phlebotomy at intervals.
24
Q
HH - Phlebotomy can improve:
A
- Cardiac function.
- Diabetes.
- Skin hyperpigmentation.
25
HH - Phlebotomy CANNOT improve:
1. Arthropathy.
2. Established cirrhosis.
3. Testicular atrophy.
4. Cardiomyopathy.
26
HH - Tx - Iron chelation (deferoxamine):
Reasonable alternative when phlebotomy IS RESTRICTED BY ANEMIA.
==> It is also the 1st line therapy for iron overload because of ineffective erythropoiesis.
27
HH - Tx - What to avoid?
VITAMIN C.
28
AAT Def. - Lung and liver disease?
1. ABSOLUTE AAT deficiency leads to LUNG disease ALONE.
| 2. RELATIVE AAT deficiency leads to LIVER +/- LUNG disease.
29
AAT def. - Lung disease results from ...?
An imbalance between destructive neutrophil elastase + protective AAT in the lung.
30
AAT def. - Liver injury results from ...?
Intrahepatocytic AAT accumulation within the RER.
31
MC GENETIC cause of PEDIATRIC LIVER DISEASE:
AAT deficiency.
32
MC genetic cause of COPD:
AAT def.
33
AAT def. - Clinical presentation as early as?
4-8 weeks.
1. Persistent jaundice.
2. Elevated aminotransferases.
3. Hepatomegaly.
34
AAT def. - Portal HTN may develop in ...?
Late childhood or early adolescence.
35
AAT def. may rarely be associated with:
1. Necrotizing panniculitis.
| 2. WEGENER.
36
AAT def. - Dx - When to consider screening?
In adults with chronic idiopathic hepatitis OR cryptogenic cirrhosis.
37
AAT def. - Dx - How to screen first?
Using SERUM AAT levels.
38
AAT def. - Dx - When to obtain the phenotype?
Phenotype analysis if AAT level is below normal.
==> ZZ phenotype associated with advanced liver disease.
39
AAT def. - Histopathology:
PAS(+) + Diastase-resistant globules in hepatocytic ER.
40
AAT def. - Tx - Under investigation?
IV infusions of AAT derived from pooled plasma or obtained by recombinant DNA methods.
==> Under investigation for LUNG disease.
==> NOT successful for LIVER disease.
41
AAT def. - Tx - Liver transplantation?
The ONLY VIABLE THERAPY for the liver disease component ==> CURATIVE.
==> 5y post-transplant survival of 80-85% in adults.
42
Wilson - ATP7B mutation:
==> Decr. biliary EXCRETION of hepatocellular copper.
==> Cu accumulation in the liver + brain + cornea + kidneys with subsequent injury thought to caused by oxidative stress.
43
ATP7B mutation also prevents integration ...?
Of copper into ceruloplasmin (ie apoceruloplasmin).
==> Shortens ceruloplasmin's half-life ==> Causing lower blood concentration.
44
Wilson - Prevalence:
30/ million.
45
Wilson disease - Acute liver failure can present with ...?
1. COOMBS-NEGATIVE hemolytic anemia.
| 2. Acute renal failure.
46
Wilson - AP?
Inappropriately SUBNORMAL.
47
Wilson - In 1 study, AP/Bilirubin ratio ...?
AP/Bil <4 + AST/ALT >2.2 ==> 100% sens and spec for identifying acute liver failure because of Wilson disease.
48
Wilson - Can also affect with other organs (besides liver and neuro/psychiatric abnormalities):
1. Kidneys (nephrolithiasis).
2. Heart (cardiomyopathy).
3. Pancreas (pancreatitis).
4. Endocrine system (hypoparathyroidism, infertility).
5. Skeletal system (osteoporosis).
49
Wilson - Dx - When to suspect?
Consider in ANY individual between ages 3 and 55 with acute hepatitis or jaundice of unclear causes.
50
Wilson - Dx - Kayser-Fleischer rings are present in ...?
95% of pts with NEUROLOGIC manifestations.
==> ONLY 40-60% of pts with mainly HEPATIC manifestations.
51
Kayser-Fleischer rings specific for Wilson?
NOT specific ==> Can manifest in CHRONIC CHOLESTATIC DISEASES.
52
Wilson - Dx - Serum ceruloplasmin?
Usually markedly LOW.
==> May be NORMAL or even MILDLY ELEVATED in the setting of acute inflammation.
53
Wilson - Dx - Urine copper excretion?
Typically >100μg, but even levels greater than 40μg warrant further work-up
==> NOT specific; levels greater than 100μg can be seen in AIH + other chronic liver diseases.
54
Wilson - Dx - Penicillamine challenge during 24h urine collection?
Has only been standardized for children.
55
Wilson - When to liver Bx?
When biochem is indeterminate.
==> Liver Bx for copper quantification and histology.
56
Wilson - Liver Bx results?
1. Copper >250μg/g of dry liver weight confirms diagnosis.
| 2. Copper <50μg/g in UNTREATED pts EXCLUDES Wilson.
57
Wilson - Histopathology:
Early histology shows:
1. Micro/macrovesicular steatosis.
2. Glycogenated hepatocytic nuclei.
3. Focal necrosis.
58
Wilson - Tx - Primary Tx:
CHELATION with oral D-penicillamine or trientine.
==> TRIENTINE is better tolerated and more commonly used in the USA.
==> Neurologic exacerbation after starting Tx is more common with D-penicillamine.
==> Monitor Tx using 24h urinary copper excretion.
59
Wilson - Tx - Role of oral zinc?
Induces enterocyte METALLOTHIONEIN ==> Binds dietary copper and prevents its GI absorption.
==> Use in PREsymptomatic pts or those on maintenance Tx.
60
Wilson - Which foods to avoid?
Shellfish, mushrooms, chocolate, organ meats ==> High Cu concentrations.
61
Wilson - Liver transplantation?
Corrects the fundamental defect in hepatic copper excretion and should be offered to pts with advanced or acute fulminant disease.
62
Pregnancy-specific liver diseases - Abnormal liver tests occur in ...?
3-5% of all pregnancies.
63
Pregnancy-specific liver diseases - Etiology:
Several different disease processes but NO clearly defined causes.
64
Pregnancy-specific liver diseases - Pathogenesis?
Abnormal INTRAMITOCHONDRIAL fatty acid oxidation has been linked to acute fatty liver of pregnancy (AFLP).
==> This is LESS established in HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome.
65
Pregnancy-specific liver diseases - Mutations?
1. Several possible mutations, particularly of long-chain 3-hydroxyachyl-CoA dehydrogenase (LCHAD).
2. Babies of mothers with AFLP should undergo genetic screening for LCHAD mutations.
66
Pregnancy-specific liver diseases - All pregnancy-specific liver diseases tend to be recurrent in subsequent pregnancies, except for ...?
AFLP.
==> Notable exception is women who carry LCHAD mutation ==> Recurrence in 20-70% of subsequent pregnancies.
67
Viral hep - MC CHRONIC VIRAL HEP WORLDWIDE?
HBV.
68
Viral hep - MC CHRONIC VIRAL HEP IN THE USA?
HCV.
69
HAV - How many are positive for Anti-HAV in the USA?
37%.
70
HAV - Incubation period:
2 to 6 weeks.
71
HAV - Transmission:
F-O transmission.
72
HAV - Several clinical patterns:
1. Self-limited hep +/- jaundice (typical).
2. Prolonged cholestasis (uncommon).
3. Protracted relapsing course (uncommon).
4. Fulminant liver failure (rare).
73
HAV - What percentage of pts develops a prolonged and relapsing course and with what is it associated?
2-15%.
1. Arthritis.
2. Vasculitis.
3. Cryoglobulinemia.
==> Relapses resemble the original episode, including serum anti-HAV IgM positivity.
74
HAV - Who is at risk for fulminant liver failure?
1. Elderly.
| 2. Those with concomitant chronic liver disease.
75
HAV - Chronic infection?
NEVER results in chronic infection.
76
HAV vaccines for:
1. Travelers to endemic areas.
2. Military workers.
3. IV drug users.
4. Chronic liver disease.
5. Family members of infected pts.
77
HAV - Post exposure proph?
Ig prophylaxis is 80-90% effective if given WITHIN 2 WEEKS following exposure.
78
HAV - Role of prednisolone?
In the PROLONGED CHOLESTATIC variant.
==> 30mg daily tapered over 21 days ==> MAY shorten the duration of JAUNDICE/PRURITUS.
79
HBV - Epidemiology:
350 million individuals chronically infected worldwide.
==> Carrier rates vary greatly depending on geographic region.
80
HBV - 3 categories of prevalence:
1. LOW (0.1-2%) ==> USA, Australia, Western Europe.
2. INTERMEDIATE (3-7%) ==> Japan, Mediterranean basin, Latin America, Middle East.
3. HIGH (8-20%) ==> China, Southeast Asia, sub-Saharan Africa.
81
What percentage of chronic HBV carriers eventually develops serious complications?
15-40%.
82
High risk for vertical transmission?
85-90% in mothers with HIGH SERUM HBV DNA levels + Presence of HBeAg.
83
HBV - High-risk adults:
1. Health care workers.
2. IVDA.
3. Hemodialysis pts.
4. MSM.
5. Sexually promiscuous individuals.
6. Institutionalized pts.
7. Immigrants from HBV-endemic regions.
8. Household members of chronic carriers.
84
HBV - Chronic hep and fulminant liver failure?
<5% ==> Chronic hep.
0.1-0.5% ==> Fulminant liver failure.
85
HBV - Chronicity for neonates and 1-5yo?
Neonates ==> 90% chronic hep B AT BIRTH.
1-5yo ==> 25-50%.
86
HBV - Mortality from fulminant course?
80%.
87
HBV - What is associated with an increased risk of HCC, even without cirrhosis?
Persistent presence of HBeAg + Elevated serum HBV DNA.
88
HBV - Incubation?
1-4 months.
89
HBV - Symptomatic acute hep (eg abdominal pain, low-grade fever, nausea, jaundice) occurs in ...?
30% OF ADULTS.
10% OF CHILDREN younger than 4 years of age.
==> Clinical symptoms usually normalize after 1 to 3 months.
90
HBV - Chronic inactive carriers with normal liver chemistries?
1. Presence of anti-HBe.
2. Minimal serum HBV DNA.
3. At risk for HCC.
==> This phase of the disease is also known as IMMUNE TOLERANCE.
91
HBV reactivation:
1. Presence of anti-HBe.
2. High serum HBV DNA.
3. Intermittently elevated ALT.
==> Can occur in immunosuppression.
92
HBV - Extrahepatic manifestations:
10-20% of chronic HBV.
1. PAN.
2. Membranous or MPGN.
3. Mixed cryoglobulinemia.
93
HBV - Dx:
1. Serology.
| 2. Positive HBV DNA PCR.
94
Serologic Dx of HBV - HBsAg seen in:
1. Acute infection - Early period.
2. Chronic infection.
3. Reactivation/Exacerbation.
95
Serologic Dx of HBV - Anti-HBs:
1. Acute infection, recovery period.
2. Resolved previous infection.
3. HBV immunization.
96
Serologic Dx of HBV - HBc-IgM:
1. Acute infection, early period.
2. Acute infection, window period.
3. Reactivation/Exacerbation (+/-).
97
Serologic Dx of HBV - HBc-IgG:
1. Acute infection, window period.
2. Acute infection, recovery period.
3. Chronic infection.
4. Reactivation/exacerbation.
5. Resolved prenious infection.
98
Serologic Dx of HBV - HBeAg:
1. Acute infection, early period.
2. Chronic infection (+/-).
3. Reactivation/exacerbation (+/-).
99
Serologic Dx of HBV - Anti-HBe:
1. Acute infection, window period.
2. Acute infection, recovery period.
3. Chronic infection (+/-).
4. Reactivation/Exacerbation.
5. Resolved previous infection.
100
Serologic Dx of HBV - HBV DNA:
1. Acute infection, early period.
2. Acute infection, window period.
3. Acute infection, recovery period.
4. Chronic infection (variable).
5. Reactivation/exacerbation.
101
HBV - Indications for treatment - HBeAg (+):
HBV DNA >20.000 IU/mL +
ALT >2X normal OR moderate inflammation/significant fibrosis on liver Bx.
102
HBV - Indiciations for Tx - HBeAg (-):
HBV DNA >2.000 IU/mL +
ALT greater than 2x normal OR moderate inflammation/significant fibrosis on liver Bx.
103
HBV - Indications for treatment - Presence of cirrhosis:
Presence of cirrhosis +
HBV DNA >2.000 IU/mL OR persistent ALT elevation.
104
HBV - Tx - Drugs:
1. Standard IFN-a.
2. Peg IFN-a.
3. Nucleos(t)ide analogues ==> Lamivudine, adefovir, entecavir, tenofovir, telbivudine.
==> Are all USA FDA-approved for the Tx of chronic HBV.
105
HBV - Tx - Role of IFN-a:
Administered for a PREDEFINED duration and has the HIGHEST rate of HBeAg seroconversion (up to 50%).
==> Significant side effects (eg flu-like symptoms, bone marrow suppression, hair loss, and mood changes).
106
HBV - Tx - Role of IFN-a - Predictors of HBeAg seroconversion include:
1. Elevated pretreatment ALT.
2. High histologic activity index.
3. Low serum HBV DNA.
4. HBV genotypes A and B.
107
HBV - Tx - Role of IFN-a - Contraindications?
In decompensated liver disease.
108
HBV - Tx - Role of entecavir and tenofovir:
Most impressive reductions in HBV DNA + The LOWEST resistance rates among the nucleos(t)ide analogues.
==> Variable durations of Tx depend on pretreatment HBeAg status and viral response.
109
HBV - Tx - Role of entecavir and tenofovir - Durations of therapy:
1. HBeAg (+) ==> Continue for AT LEAST 6 MONTHS AFTER HBeAg seroconversion + Undetectable HBV DNA.
2. HBeAg (-) ==> Continue INDEFINITELY until HBsAg clearance.
3. Decompensated cirrhosis ==> LIFELONG Tx.
110
Acute HBV - Antiviral Tx?
NOT NEEDED.
>95% spontaneous recovery among immunocompetent individuals.
111
Acute HBV - When to use antiviral Tx?
Fulminant liver disease and protracted severe course.
112
Acute HBV - WHAT antivirals to use?
1. May use lamivudine or telbivudine when anticipating short Tx duration.
2. Less preferable ==> Adefovir (weak antiviral activity, nephrotoxic potential) + Tenofovir (nephrotoxic potential).
113
Acute HBV - IFN-a?
CONTRAINDICATED.
114
HBV and HCC screening?
Routine HCC screening in HIGH RISK HBV carriers:
1. Asian men >40.
2. Asian women >50.
3. Africans >20.
4. Cirrhotic pts.
