L11: Hepatitis/Liver disease Flashcards
1
Q
Most prevalent liver disease
A
Nonalcoholic fatty liver disease
2
Q
Spectrum of AST or ALT values for liver disese
A
Shock liver/acetominophen (10,000) > Acute Hep A, B, C > ETOH> Chronic Hep B and C > Cirrhosis > normal (15-30)
3
Q
Hepatocellular pattern
A
Increased liver transaminases: ALT + AST
+/- Elevated ALP
4
Q
AST:ALT>2
A
Alcoholic liver disease
5
Q
ALT>AST (AST:ALT<1)
A
NASH
Acute or chronic viral hepatitis
6
Q
Cholestatic pattern
A
Elevated ALP and GGT
7
Q
Fatty liver aka
A
hepatic steatosis
8
Q
Non-alcoholic is defined as
A
<20 g ETOH/day (less than2-3 drinks/day)
9
Q
Non-alcoholic steatohepatitis (NASH)
A
fatty liver with inflammation of liver with hepatocyte injury→ higher risk of fibrosis, cirrhosis→ worse prognosis, progression
10
Q
Isolated steatohepatitis (NAFLD)
A
fatty liver without injury or fibrosis→ low risk of progression to cirrhosis (but still not considered benign)
11
Q
Diagnosis of NASH
A
Biopsy is gold standard
but Fibroscan, MRI, MRE used more often
12
Q
Presentation of NAFLD/NASH
A
Asymptomatic
Fatty infiltration incidentally seen on imaging→ exclude other causes, ETOH
13
Q
NAFLD/NASH on liver biopsy
A
biopsy is not necessary, but you would see: steatosis, inflammation, +/- fibrosis
14
Q
NAFLD/NASH labs
A
Hepatocellular pattern Mild Elevation ALT + AST <300 IU/ml Ferritin elevated (53-62%) → inflammation Hyperlipidemia Elevated fasting glucose ALP elevated in ⅓ GGT elevated \+/- Weakly positive autoimmune factors→ get bx to confirm Normal albumin, bilirubin and INR
15
Q
NAFLD/NASH
A
Exclude all other causes of elevation of liver tests Order Fibroscan/calculate FIB- 4 Exercise + weight loss (DOC) Body weight reduction associated with histological improvement Minimize ETOH, Modify CVD risk factors Control diabetes and hyperlipidemia → compensated cirrhotic→ Statins Monitor LFT/liver tests Vaccinate for Hep A & Hep B
Liver bx→ confirm dx (before tx w/ meds), exclude concomitant liver disease, assess degree
16
Q
DOC for NAFLD/NASH
A
Exercise + weight loss
17
Q
Hereditary disorder of iron metabolism→ genetic mutation → increased GI absorption of iron → accumulation of iron in the liver, pancreas, heart, adrenals, testes, pituitary, skin, kidney
A
Hereditary Hemochromatosis
18
Q
Bronze diabetes
A
Hereditary Hemochromatosis triad:
DM
Bronze pigmentation of skin
Cirrhosis
19
Q
Hereditary Hemochromatosis presentation
A
Family history or incidental note ↑ AST + ALT (Northern Europeans)
Initially non-specific symptoms
Fatigue, malaise, RUQ discomfort
20
Q
Hereditary Hemochromatosis labs
A
Elevated Liver tests AST, ALT, Alk Phos
Screen→ serum Fe + TIBC and ferritin
• Fe/TIBC = TS (transferrin saturation)
• TS > 45 and/or ferritin > 200 ng/mL (men) > 150 ng/mL (women) → GI- HFE* mutation analysis
Confirmed with genetic testing +/- liver biopsy
21
Q
Hereditary Hemochromatosis management
A
Regular phlebotomy (hematologist )
Prevent cirrhosis from iron overload
Cirrhosis screen q 6 months (US +/- AFP)
Avoid Vit C, iron supplements, ETOH
Avoid uncooked shellfish (oysters) while iron testing
22
Q
Hereditary Hemochromatosis screening guidelines
A
Genetic screen→ HFE genotype
Iron testing
Screen in pts with: Elevated Liver tests (AST/ALT) Abnormal iron studies First degree relative history Evidence of liver disease* Suggestive symptoms
23
Q
Late Hereditary Hemochromatosis
A
4th-5th decade Hepatomegaly hepatic insufficiency cirrhosis (+/-complications) DM impotence, arthralgia (2nd/3rd MCP joints) bronze pigmentation of skin Cardiomegaly with or without CHF Bronze Diabetes
24
Q
Very rare hereditary disorder of copper metabolism
Autosomal recessive mutation→ decreased excretion of copper into
bile→ accumulation of copper in liver→ liver capacity for copper exceeded→ released into bloodstream→ accumulates in brain, cornea, joints, kidney, heart, pancreas
A
Wilson’s Disease
25
Wilson's disease presentation
Ages 3-55
Hepatic Symptoms
Neurologic/psychiatric symptoms→ tremor, dysarthria, incoordination/ataxia, parkinsonism personality/behavioral changes
Kayser-Fleischer ring→ fine pigmented brownish/gray-green granular deposits on cornea
→ detected by naked eye or ophthalmoscope
26
Wilson's Disease treatment
Refer to GI with training in Hepatology
Chelating agents:
D-penicillamine
Trientine
27
Wilson's Disease labs
Mildly Elevated AST/ALT
Alk phos→ normal or low
Reduced <5 ug/dl *serum ceruloplasmin* (initial screen)
→ plasma copper-carrying protein
Ophthalmologist eval.
Increased *24 hour urinary copper*
Confirmed with liver biopsy +/- molecular testing*
First degree relative screening→ genetic analysis
28
Pathognomonic for Wilson's Disease
Kayser-Fleischer ring + neuro manifestations
29
D-penicillamine
Copper chelating agent
30
Trientine
Copper chelating agent
31
Severe alpha-1 antitrypsin deficiency
Severe→ < 11 umol/L
32
alpha-1 antitrypsin deficiency presentation
non-smoker with emphysema at a young age (<45 years)
neonatal cholestasis
childhood cirrhosis
33
alpha-1 antitrypsin deficiency screening
Emphysema in :
• Young patient (<45 yo)
• Non-smoker or minimal smoker
• Predominant basilar changes on CXR
Adult onset asthma
• Persistent airflow obstructive pattern on post bronchodilator spirometry testing
Clinical findings or history of unexplained chronic liver disease
• Current or prior elevation of liver tests
• Patient with cirrhosis +/- portal HTN (nodular small liver, splenomegaly, low platelets)
Family hx of emphysema and/or liver disease
History of panniculitis (skin)
34
alpha-1 antitrypsin deficiency labs
Mild elevation of AST/ALT
Decreased serum alpha-1 antitrypsin
Alpha-1 antitrypsin genotype (MM=wildtype)
Rule out other causes
+/- Liver biopsy
35
alpha-1 antitrypsin deficiency treatment
Liver transplant
Genetic counseling
36
Autoimmune hepatitis presentation
Variable
Asymptomatic w/ elevated liver enzymes
Cirrhosis
Non-specific symptoms→ Fatigue, Malaise, Anorexia, Pruritus, Abdominal Pain, Arthritis
Acute severe liver disease→ Acute hepatitis +/- liver failure (⅓)
→ Hepatosplenomegaly
→ Jaundice, Fever
37
Labs for autoimmune hepatitis
* Antinuclear antibodies (ANA) (10%)
* *Anti-smooth muscle antibodies* (ASMA) (90%)
* +/- Liver kidney microsomal antibody (LKMA)
* antibody to liver cytosol (LKC-1 (30-50%)
* Anti-soluble Liver Antigen (SLA) → children
* Anti-liver pancreas antigen (LPA) → children
* Elevated bilirubin
* Elevated ALP→ 3x ULN
* Elevated PT/INR
* Albumin (decreased)
* *AST/ALT*→ 7-10x ULD
* High IgG titer
38
Autoimmune hepatitis management
Refer to Gastroenterologist/ hepatologist
Depends on disease activity
Prednisone +/- Azothioprine (Imuran)
• Continue until remission (normalization of LFT)
• Watch for side effects from steroids/Imuran with labs and follow-up
• Maintain on lowest dose of Imuran for continued remission
• Monitor bone density (DEXA)
Liver transplant→ fulminant liver failure
Vaccinate for Hep A and Hep B
39
Prednisone +/- Azothioprine (Imuran)
mainstay of tx for Autoimmune hepatitis
40
Acute hepatitis
Hep A, E
41
Fecal-oral hepatitis
Hep A, E
42
Vaccines for hepatitis
Hep A, B
43
Hepatitis that's fatal in pregnancy
Hep E
44
Hep A background/transmission
Inadequate sanitation/clean water
Endemic→ Asia + Africa
Recent homeless outbreaks
Fecal-oral, person to person (oral-anal sex), contaminated food or water
45
Hep A presentation
```
Acute
Children <6 years asymptomatic
Adults symptomatic
Incubation→ 15-50 days (avg 28)
Prodrome
Flu-like→ fever, N/V/A, malaise, RUQ pain
Icteric phase
Jaundice→ 1 week after symptom onset
*Hepatomegaly*, dark urine, pruritus, light colored stool
```
46
Hep A labs
Increased AST/ALT (>1000 or 15x ULN)
Increase bilirubin + ALP
(+) IgM anti-HAV→ acute
(4 months)
(+) IgG anti-HAV→ immunity
47
Hep A management
Supportive→ fluids, rest→ recovery in 6 months
Hospitalize→ elderly, multiple comorbidities, underlying liver disease, fulminant liver failure
Infection precautions→ hand washing, food handling, food prep/cook temp >185 F, chlorine/bleach for cleaning
Notify local health department
Non immune contacts→ HAV IgG and/or vaccination
Prevention→ vaccination
48
Hep A patients who get hospitalized
Elderly
multiple comorbidities
underlying liver disease
fulminant liver failure
49
Nonimmune contacts can get ____ as Hep A prophylaxis
HAV IgG
| Vaccine
50
Hep B transmission
DNA virus
| Blood/blood derived body fluid, sexual, parenteral contact (needle sharing), perinatal transmission during delivery
51
Hep B is a ____ virus, Hep C is a ____ virus
Hep B: DNA virus
Hep C: RNA virus
This means Chronic Hep C can be cured/cleared from the body because it doesn't have DNA intermediates. Chronic Hep B has no cure.
52
Hep B presentation
```
Incubation→ 45-160 days
Symptomatic (30%)→ N/V, RUQ pain, jaundice, malaise, arthralgias, fever.
Increased bilirubin, ALP
Increased ALT >15x
Subclinical (70% adults, 90% children)
Chronic→ <5% adults, most infants
Fulminant hepatic failure (rare)
```
53
Leading cause of cirrhosis + hepatocellular carcinoma
Chronic Hep B
54
Hep B management
Supportive→ 95% of adults recover with immunity
| +/- antiviral therapy→ acute liver failure or protracted course
55
Hospitalize these patients with Hep B
Underlying liver disease
Multiple comorbidities
Older/Elderly→ more severe in age >60 years
Signs of liver failure→ transfer to liver transplant center (rare)
56
Who most commonly gets chronic hepatitis B?
Children <5 years
| Immunocompromised
57
HBsAg
(+) active disease→ acute or chronic
(+) >6 months→ chronic
1st detectable marker of infection→ 1-9 weeks after exposure→ before onset of symptoms
*Hallmark of active infection*
58
Anti-HBs/HBsAb
(+) immune→ vaccine or resolved infection
Appears after disappearance of HBsAG→ indicates end of acute infection phase→ recovery & immunity
Hep B vaccine→ exposure to HBsAg→ (+)
59
Anti-HBc
(+) IgM→ acute
(+) IgG→ previous
(+) Total→ previous
IgM→ shortly after HBsAg detected, or HBsAg cleared but Anti-HBs not yet detected
*Acute/recent infection*→ 4 months
IgG→ *prior or resolving infection*→ forever
Total= IgM + IgG → *prior exposure*
60
HBeAg
(+) → high viral load, actively replicating
(-) → low viral load
Marker of infection→ higher levels of HBV DNA
61
Anti-HBe
(+) → predictor of long term clearance
(+) anti-HBe + (-) HBeAg→ lower levels of HBV DNA
62
HBsAg (-)
Total anti HBc (-)
Anti-HBs (-)
Susceptible to HBV infection
63
HBsAg (-)
Total anti HBc (+)
Anti-HBs (+)
Immune to HBV by natural infection
64
HBsAg (+)
Total anti HBc (+)
Anti-HBs (-)
IgM anti-HBc (+)
Acute infection with HBV
65
HBsAg (+)
Total anti HBc (+)
Anti-HBs (-)
IgM anti-HBc (-)
Chronic infection with HBV
66
HBsAg (-)
Total anti HBc (+)
Anti-HBs (-)
Interpretation unclear:
* **1. Resolved infection (most common)***
2. False (+) anti-HBc→ susceptible
3. Low level chronic infection
4. Resolving acute infection
67
HBsAg (-)
Total anti HBc (-)
Anti-HBs (+)
Immune to HBV by vaccination
68
most common cause of liver transplantation with hepatocellular carcinoma
Hep C
69
Hep C
RNA virus
Blood/blood derived body fluid transmission
Most develop chronic infection
```
Risk:
IVDU, tattoos, piercings
Transfusion <1992
Received clotting factors <1987
Know exposure (needle stick)
Children born to HVC (+) mother (rare)
Sexual contact (rare, >MSM)
```
70
Acute Hep C infection
```
14-180 days post exposure
Asymptomatic (most)
Symptomatic→ jaundice, fatigue, fever, nausea, vomiting, RUQ discomfort (10-20%)
AST/ALT→ elevated, <300 IU/l )
Bilirubin elevated
```
(-) Hep C Ab with (+) RNA viral load
OR
(+) Hep C Ab prior had (-) Hep C Ab
71
Chronic Hep C
Most asymptomatic and diagnosed by ↑LFT/liver tests→ AST + ALT <100
+/-fatigue, wt. loss, anorexia, nausea, RUQ discomfort
Cirrhosis w/in 20-30 years (10-20%) → watch for complications
Many present in 20s due to IVDU
72
Screening for Hep C
*Born 1945-1965 w/o prior assessment of risk*
Received a blood transfusion or organ transplant before July 1992 or clotting factor concentrates before 1987
Injected/intra-nasal illegal drugs
Long term dialysis
Children born to HCV positive women
Healthcare workers and public safety workers after needle sticks, sharps or mucosal exposure to HCV (+) blood
Evidence of chronic liver disease (PE or labs)
IVDU→ annually
Pregnant women
Unregulated Tattoo or body piercings
Past incarceration
HIV infection (annually if they have unprotected sex)
Sexually active persons about to start PEP (post exposure prophylaxis)
73
Hep C labs
```
Varying ALT patterns:
Normal→ Chronic
Acute→ 100s
Cirrhosis→ AST>ALT
LFTs can rise and fall
```
74
Hep C management: lifestyle
Screen for HAV + HBV→ not immune→ Vaccinate
Non-infected sexual partner testing→ Sexual transmission risk low(<2%, higher MSM)
Avoid ETOH intake
Don’t donate blood, organs, share toothbrushes, nail clippers, razors
Cover open cuts on skin
75
Hep C management: preventing complications/cure
Monitor signs/complications of cirrhosis
Check for co-infection with HBV (HBsAg and HB core Ab), other causes of liver disease, HIV
Refer to GI for treatment→ *Cure of Hepatitis C does not preclude re-infection*
Direct-acting antiviral agents→ oral, 8-16 weeks
Regime based on: genotype, treatment (naïve or experienced), cirrhotic and non-cirrhotic +/- viral load
Treatable and curable in most patients
*Resistance Associated Variant Analysis sometimes needed prior to treatment*
HVC→ no known intracellular reserves, no DNA intermediates→ impact viral replication→ clearance→ cure
76
Hep C serology basics
Hep C Ab takes 8-12 weeks to develop
| RNA viral load develops 2-4 weeks after infection
77
(-) Hep C Ab with (+) RNA viral load
Acute Hep C infection
78
(+) Hep C Ab prior had (-) Hep C Ab
Acute Hep C infection
79
(+) Hep C ab (-) RNA viral load
****resolved (treated) Hep C****
80
Hepatitis D
Acute hepatitis symptoms
Seen only in conjunction with Hep B→ Associated with more severe course
Always test Hep B pts
Management→ Eradicate Hepatitis B (refer to GI/hepatology)
81
Hep D serology
Delta virus RNA with +HBsAg
| Used to diagnose Hep D in Hep B pts
82
Hep E
Transmission→ Fecal-oral
Presentation→ Acute hepatitis symptoms
similar to Hep A.
Travel to developing countries in last 1-2 months (highest in East + South Asia).
Fatal in approx 20% of infected pregnant women, <1% otherwise
More severe and greater mortality in 2nd in 3rd trimester
Management→ Supportive
83
Hep E serology
Hepatitis E RNA
84
Metabolic syndrome criteria
```
3 of the 5:
Obesity
HTN
DM
Hyperlipidemia
Hypertriglyceridemia
```
*big risk for NASH/NAFLD*
