Liver Flashcards
1
Q
What is acute liver failure?
A
onset of liver injury, hepatic encephalopathy, & coagulopathy (INR > 1.5) in patients with no prior hx of liver disease
rapid decline of liver func.
2
Q
MCC of liver acute liver failure?
A
Tylenol OF
3
Q
s/s of acute liver failure?
A
AMS (early: personality change > lethargy> coma)
Cerebral Edema
Coagulopathy
Multiple Organ Failure
Ascites and anasarca
Serial Physical Exams: shrinking liver
4
Q
Clinical features of acute v. subacute hepatic failure?
A
Encephalopathy develops within 1- 4 weeks of onset of liver injury
Encephalopathy develops 12- 24 weeks after onset of liver injury
5
Q
lab findings in acute liver failure?
A
Severe coagulopathy ( increased PT/INR)
CBC: leukocytosis
BMP: hyponatremia, hypokalemia, hypoglycemia
LFTs: marked elevation of bilirubin, ALT, AST
6
Q
Tx of acute liver failure?
A
Admit: transfer to a liver transplant center
Continuous monitoring and supportive care
Await spontaneous resolution
If recovery seems unlikely: prepare for liver transplantation
7
Q
What is hepatitis? MCC?
A
Acute or chronic hepatocellular damage
lots of causes
MCC acute &chronic: viral
8
Q
How are Hepatitis A& E transmitted?
A
by fecal-oral route, do not cause chronic infection
9
Q
How are viral Hep B,C & D transmitted?
A
transmitted parenterally or via mucous membrane contact, can progress to chronic infection
hx: IVDA, tattoos, infx mother, blood transfusion
10
Q
What are the dif. categories of acute hepatitis?
A
self limited (HAV, HEV)
acute liver failure
cholestatic hep (HAV)
Relapsing hep (HAV)
11
Q
patho of acute viral hep?
A
Cell-mediated immune mechanisms hepatocyte injury (degeneration and apoptosis)
12
Q
s/s of self limited acute viral hep?
A
asxs-> lots
prodromal: GI sxs, flu like sxs, abrupt onset in HAV & HEV
Then: jaundice, pruritis
13
Q
PE findings in acute self limited hep?
A
Mild enlargement/slight tenderness of liver
Mild splenomegaly and posterior cervical lymphadenopathy
14
Q
s/s of acute cholestatic viral hep?
A
Severe jaundice for several months
Prominent pruritis
Persistent anorexia and diarrhea (small percentage of patients)
Excellent px for complete recovery
15
Q
s/s of relapsing acute hepatitis?
A
Sxs recur weeks – months after improvement/apparent recovery
Arthritis, vasculitis, and cryoglobulinemia (excess proteins/cryglobulins in the blood) may be seen
Px is excellent for eventual complete recovery ( may have multiple relapses)
16
Q
lab findings in self limited acute viral hepatitis?
A
ALT & AST > 500 units/L, ALT>AST
Total bilirubin: norm
Alkaline phos: normal to mild elevation
Prolonged PT/INR: normal to mild elevation
Albumin: normal to mild decrease
CBC: +/- mild leukopenia
Possible lymphocytosis
17
Q
Labs seen in cholestatic viral hep?
A
Bilirubin ≥20 mg/dL
Elevation of alkaline phos
Initial elevation of ALT/AST may decrease despite persistent cholestasis
18
Q
labs seen in relapsing viral hepatitis?
A
Elevation of ALT, AST, Bilirubin recurs after normalization
Usually relapses do not exceed previous levels
19
Q
Tx for self limited and relapsing acute hepatitis?
A
Outpt unless severe dehydration
Adequate POs
No etoh
Rest
DC non-essential drugs
20
Q
Pharm tx for self limited and relapsing acute hepatitis
A
HAV, HEV, HDV – no specific drug treatment
HCV – if spontaneous resolution does not occur in 3 months use oral antiviral as per chronic HCV tx guidelines
HBV – tenofovir or entecavir only indicated in severe cases
21
Q
25
A
25
22
Q
Risk factors for Hep A?
A
living in endemic region
High prevalence areas = Africa and parts of Asia and Latin America
close personal contact with an infx person
men who have sex with men
known foodborne outbreak
23
Q
s/s of Hep A?
A
Incubation: ~28 days
preicteric phase 5-7 d > Fever likely to occur with HAV
icteric phase Jaundice peaks typically at 2 weeks
24
Q
Dx tests for Hep A?
A
IgM Antibody to HAV (Anti-HAV)
-detected 5-10 days before sxs onset and stay for 3-6mo
IgM is replaced with IgG anti-HAV
-stays helpful for life
25
Tx for Hep A?
supportive
nearly all recovered in 6 months
26
Pt Ed for Hep A?
good handwashing, disposal of wastes
careful food handling
Immunizations: HAV vaccination
Avoid Tylenol and ETOH
children should stay home for 1 wk
27
Hep A post-exposure prophylaxis?
for anyone recently exposed?
give ASAP, within 2 wks
Healthy persons 12mos – 40 yo: HAV vaccine
>40yo, <12 mos., chronic liver disease, immunocompromised: Immune globulin
28
Epidemiology of Hep E?
Highly endemic in Mexico, Cuba, Asia, Africa, and the Middle East
29
How is Hep E transmitted?
Can be spread by animals, most commonly swine
Contaminated drinking water is common source of infection
Consumption of undercooked pork, deer meat, shellfish
30
Clinical features of Hep E?
Abrupt onset of prodromal sxs
Acute liver failure occurs in high frequency (10-20%) in pregnant women with HEV (especially in 3rd trimester)
31
Dx of Hep E?
IgM Anti-HEV detectable for at least 6 wks (usu. first few months)
IgM is replaced with IgG Anti-HEV which is usually only detectable for 12 – 20 mos
HEV RNA test confirms and quantifies presence of HEV
- stool sample
- good for immunocompromised
32
Prevention of Hep E?
NO vaccine in US, no immune globulin
- good sanitation
- avoid unpurified water
- avoid raw pork and venison
33
What are the blood-borne hepatits?
HBV, HDV, HCV
Linked to chronic liver disease
Associated with persistent viremia
34
What is HBV?
DNA virus transmitted by percutaneous and permucosal routes
sexually transmitted disease
may result in a self-limited disease requiring no treatment
may also result in chronically infx state
35
Characteristics of HBV infx?
neonates: asxs, most chronic carries
adult: asxs, some have sxs icteric hepatitis
10-30% risk of developing cirrhosis
36
Patho of HBV?
Most of the liver injury occurs due to the host immune response to HBV, a cell-mediated response against HBcAg
37
What are some sig. risk factors for Hep B?
infant born to an HBV-infected mother
Multiple sexual partners
MSM
IVDA
Asian, eastern European, or African ancestry
FHx of HBV and/or chronic liver disease
FHx HCC
Household contact with HBV
38
Dx of HBV?
70% have norm PE
Acute:
- elevated ALT
- HBsAg and Anti-HBc
Prior HBV:
-Anti-HBs, IgG anti-HBc, Anti HBe
Chronic:
- HBsAg >6 mo
- Persistence of HBeAg & HBV DNA
Inactive carries:
asxs, normal ALT, low level HBV DNA, anti-HBe, negligible infectivity
39
acute s/s of HBV?
```
Fever/chills
Malaise
Maculopapular or urticarial rash
Nausea/vomiting
Arthralgia/arthritis
```
40
Tx of HBV?
Acute – self-limiting
Fulminant – liver transplant
Chronic – anti-viral therapy, liver bx, refer to hepatology
41
Tx options for chronic Hep B?
Peginterferon alfa-2a– anti-viral, weekly SQ injections for 48 wks
-For: young, non-cirrhotic, low HBV DNA level
Nuceloside analogues– inhibit HBV replication, daily po, may require indefinite therapy
42
Goals for anti-viral HBV therapy?
Primary: sustained low or undetectable HBV DNA
Secondary: seroconvert HBeAg and HBsAg and normalize ALT
43
When dx-ing Hep B, what else should you r/o?
HIV
44
What types of Hepatitis vaccinations for we have?
A and B
Hep B: recombinant inactive HBsAg at birth and 6 mo
45
What other prevention options are there?
Hep B immune globulin (post exposure prophylaxis, new borns of + moms)
those with HBV: avoid heavy ETOH, barrier protection during sex, cover open cuts/scratches, no blood/organ/semen donations
46
Presentation of Hep B?
Most asxs, although some will present with complications such as cirrhosis, hepatocellular carcinoma, or liver failure.
47
What is HDV?
A defective RNA virus that requires presence of HBV, specifically only in the presence of HBsAg
48
When should you suspect HDV?
Fulminant HBV infection
Acute HBV infection that improves and then relapses
Progressive chronic HBV without active HBV replication
49
Labs for HDV?
anti-HDV, HDV RNA
Acute vs chronic: IgM and IgG anti-HBc
IgM Anti-HBc = co-infection
IgG Anti-HBc = HDV superinfection
50
Tx for HDV?
High dose interferon alpha and PEG IFN only approved treatments for chronic disease
Therapy is not optimal (high risk of relapse), better regimes are under investigation
51
What is HepC?
An infectious, hepatotropic virus belonging to the Flavivirus family
ss-enveloped RNA virus
52
USPSTF screening recommendations for Hep C?
high risk groups
all people born between the years of 1945 and 1965, regardless of perceived risk
53
Presentation of HCV?
Acute infection (self-limited in 15-45% of cases): Almost all patients develop a vigorous antibody and cell-mediated immune response
Persistent viremia: accompanied by variable degrees of hepatic inflammation and fibrosis over time
chronic infections
54
What can accelerate liver cirrhosis in HCV?
chronic alcohol consumption
coincidental viral infections
55
What is the main HCV genotype seen in the US, Western Europe and Japan?
Genotype 1
56
How is Hep C transmitted?
transmitted by any percutaneous blood exposure
MCly around IVDA
less freq: sexual activity, perinatally, after accidental blood contact
57
RF for HCV?
IVDA, blood transfusion (before 1992), HIV
58
Presentation of HCV?
most asxs
Prodromal/jaudice sxs
young women: many clr virus
majority will dvelop chronic infx
African Americans: less likely to spontaneously clear
59
Acute HCV infx tests?
hepatitis C antibody (Anti- HCV)- several wks after exposure
HCV RNA testing is needed to diagnose acute infection
Others:
Human interleukin-28B (IL28B) genotype CC: more frequent spontaneous resolution
IL28B genotypes CT and TT: less frequent spontaneous resolution
60
Time period for acute HCV testing?
HCV RNA detectable days from exposure – 8 wks after
ALT and AST elevated 6 -12 weeks from exposure
Anti-HCV detectable 8 weeks – several months
61
Dx of chronic Hep C?
detection of HCV RNA in the blood for at least 6 mos
usually asxs
62
What are some factors that influence the development of chronic/ progressive liver disease?
older
male
Concurrent chronic hepatitis B
HIV infection
high alcohol intake
63
Tests for chronic HCV?
EIA detects antibodies against the virus
(+) = presence of active infx
Qualitative studies used to confirm viremia, generally low limits of detection
Quantitative tests give wide dynamic range of viral loads
64
Work up for HCV?
Confirm HCV viremia (Quantitative)
Eval for co-existent liver disease and HIV
Vaccinate for HAV / HBV
Obtain viral genotype
Consider co-existent cirrhosis
Eval for ongoing substance use
Discuss transmission to spouse/sexual partners
65
Why do you care about genotype for HCV?
helps to determine tx type
66
Goal of Hep C antiviral tx?
clr virus
stabilize
sxs control
prevent comps of progressive liver disease
if already cirrhotic: clr virus before transplant
67
Pharm tx for Hep C?
antiviral therapy
1st Line: Sofosbuvir (new)
-NS5B polymerase inhibitors
usually Sofosbuvir + some other antiviral
68
What information determines tx regimen for Hep C?
HCV genotype
Has the patient been treated before?
Does the patient have cirrhosis?
69
HCV chronic infx response to tx?
RVR (rapid viral response): HCV RNA undetectable by wk 4 of trx
EOT (end of tx response): HCV RNA undetectable at the end of treatment
**SVR (sustained virologic response): undetectable HCV RNA at 12 wks after treatment completion
Nonresponse: failure to attain undetectable HCV RNA at any point during therapy
Relapse: EOT response followed by return of HCV RNA after completion of treatment
70
Factors that reduce likelihood of attaining HCV SVR?
Cirrhosis
Previous nonresponse to interferon therapy
HCV genotype 3
If Yes --> tx extended to 24 wks, adding Ribavirin
71
What is Drug-induced Liver Injury (DILI)/
Toxic Hepatitis?
one of the MCC of elevated LFTs
greater incidence in older pts
72
What drugs commonly cause drug induced liver injury?
Antimicrobials (46%)
CNS Agents
Immunomodulating agents
Analgesics
Lipid-lowering agents
LOTS more
73
Presentation of DILI?
subclinical LFT elevation --> acute liver failure
May develop in days or within several wks of substance ingestion
Liver labs may reveal: hepatoxic injury, cholestatic, or mixed
74
Dx of DILI?
hx of patient consuming a causative drug or toxin
Exclude other causes of liver disease
75
Tx of DILI?
Remove causative agent and monitor for resolution of liver injury
In severe cases of Acute Liver Failure – liver transplantation may be required
76
What is the MCC of ALF from DILI?
OD of Tylenol
toxic dose: 10-20g (lower in alcoholics or pts w/ liver disease)
77
Presentation of toxic ingestion of Acetaminophen?
30mins – 24 hrs after ingestion: GI sxs
2 days after: R sided abd pain & oliguira, elevated LFTs and prolonged PT/INR
3-5 days after: hepatic necrosis with elevated aminotransferases, renal failure in 20% of cases, ALF in 30% of cases
5-10 days after: recovery phase
78
What can indicate likelihood of death/need for liver transplant after Tylenol OD?
pH lower than 7.3
Stage 3-4 encephalopathy with PT/INR > 6.5 and Cr >3.4
Factor V level of 10% or less
79
Management of toxic Tylenol ingestion?
Obtain serum acetaminophen level
IV N-acetylcysteine (NAC) for serial doses
Charcoal can be used if it is within 1 hr of ingestion
Gastric lavage can be used within 4 hrs of ingestion
80
Spectrum of alcoholic liver disease?
Steatosis (fatty liver)
Steatohepatitis (alcoholic hepatitis)
Cirrhosis (predominate fibrogensis/scarring)
due to: chronic/excessive alcohol intake
81
Clinical features of alcoholic liver disease?
asxs-advanced liver failure
Portal hypertension can occur in alcoholic hepatitis without cirrhosis
Other sxs: fever, anorexia, nausea, RUQ pain, tender hepatomegaly, jaundice
82
Labs seen in alcoholic liver disease?
AST is usually elevated (usually not above 300)
AST > ALT, usually by a factor of 2 or more.
Alk Phos…increased
+/- other LFTs elevated
High TGs
Low: Potassium, phosphate, magnesium
High glucose
83
Dx of alcoholic liver disease? Tx?
hx alcohol abuse
exclude other liver disease
liver bx
Abstinence!
84
What can be used to dx short term px w/ worsening alcohol hepatitis?
Maddrey’s discrimination function (DF)
DF = 4.6 x (the difference between the patient’s and control prothrombin time) + serum bilirubin
> 32 = 50% mortality
85
Management of acute worsening of alcoholic hepatitis?
Alcohol Abstinence!
sufficient carbs/calories
Nutrional support
Admin micronutrients
Methoprenisone DF >32
Pentoxifylline
86
What is included in Nonalcoholic Fatty Liver Disease (NAFLD)?
Hepatic steatosis
Non-alcoholic steatohepatitis(NASH)
87
What is Hepatic Steatosis?
accumulation of triglyceride droplets in hepatocytes
If no significant inflammation or fibrosis on bx = benign condition
88
What is NASH?
necroinflammatory changes on liver bx, may progress to cirrhosis
Pathogenesis: lipotoxic injury to hepatocytes
89
RF for NASH?
Insulin resistance
Obesity
DM2
Lipid abnormalities
Medications such Tamoxifen and corticosteroids
90
Presentation of NAFLD and NASH?
usually asxs, +/- RUQ pain
elevated aminotransferase levels and/or hepatomegaly
bx needed
91
Tx NASH?
lifestyle changes:
Weight loss
dietary fat restriction
exercise
92
What is autoimmune hepatitis?
Usually young to middle-aged women
Chronic hepatitis with high serum globulins and characteristic liver histology.
Positive antinuclear antibody (ANA) and/or smooth muscle antibody in most common type
93
Autoimmune hepatitis responds to...
corticosteroids
94
s/s of autoimmune hepatitis?
onset is usually insidious
If sxs/signs do occur, may include fatigue, jaundice, and/or hepatomegaly
May present as acutely severe/fulminant
95
Labs seen in autoimmune hepatitis?
Serum aminotransferase levels may be > 1000
total bilirubin is usually increased
Alkaline phos: usually elevated
Serum gamma-globulin levels are typically elevated
Auto abs (need at least 1: ANA or smooth muscle abs, auto abs to soluble liver antigen, Anti-LMKK1)
+/- elevated serum gamma globulin
liver bx: dx, eval severity
96
Tx of autoimmune hepatitis?
Prednisone with or without azathioprine improves symptoms
97
Standard tx for autoimmune hepatits?
Prednisone taper from 30mg QD down to 10mg QD over 1 month. Then 10mg maintenance until end point.
+
Azathioprine 50mg daily until endpoint
OR
-Prednisone taper from 60mg QD to 20mg QD over 1 month. Then 20mg maintenance.
98
When do you stop tx for autoimmune hepatitis?
Ideal (satisfactory) Remission: no sxs, nl liver tests (AST/ALT ≤2 ULN, nl liver tissue (no interface hepatitis)
99
FU for autoimmune hepatitis?
If remission is achieved will need to follow with hepatologist every 3-6 months due to high-likelihood of relapse
100
What is wilson's disease?
due to a genetic abnormality inherited in an autosomal recessive manner that leads to impairment of cellular copper transport.
101
Classic presentation for wilson's disease?
age 5 -35 years
decreased serum ceruloplasmin
detectable Kayser-Fleischer rings
102
Tx for wilson's disease?
D-penicillamine
Liver transplant: indications -->
Fulminant hepatitis
Hepatic insufficiency unresponsive to medical therapy
Severe neurologic sxs
103
What is Hereditary Hemochromatosis?
An inherited disorder with impaired intestinal iron absorption that leads to iron-mediated tissue injury, iron is deposited in multiple organs
Usually suspected because of elevated iron saturation or serum ferritin or a family history.
104
Presentation of hereditary hemochromatosis?
most sxs
Cardiac disease, DM, joint disease, infx
105
What gene mutation is seen with Hereditary Hemochromatosis?
HFE gene mutation (usually C282Y/C282Y)
106
Tx for Hereditary Hemochromatosis?
serial phlebotomy to achieve iron depletion
107
What is Alpha-1 antitrypsin (AAT) deficiency?
174
108
Dx of Alpha-1 antitrypsin (AAT) deficiency?
174
109
Tx of Alpha-1 antitrypsin (AAT) deficiency?
174
110
Patho of primary biliary cirrhosis?
T-cell attack on bile ducts those genetically susceptible cannot suppress the attack gradual bile duct loss and portal scarring cirrhosis
111
Presentation of primary biliary cirrhosis?
middle-aged women
Often asxs
Fatigue and pruritis
+/-jaundice, features of cirrhosis, xanthelasma (yellow plaques on eyelid), xanthoma (yellow deposits throughout skin) , steatorrhea.
112
Labs seen in primary biliary cirrhosis?
elevated alk phos
(+) antimitochondrial antibodies (AMA)- 95%
elevated IgM
increased cholesterol.
norm biliary imaging
liver bx
113
Tx for primary biliary cirrhosis?
Cholestyramine (a bile acid resin) taking 4 g in water or juice three times daily may be beneficial for pruritus
Ursodeoxycholic acid (slows progression of damage to cells)
Liver transplant for intractable pruritis or liver failure
114
What is PSC?
181
115
PSC has a strong assoc with...
ulcerative colitis (UC) and cholangiocarcinoma
116
Presentation for PSC?
182
117
What labs are seen with PSC?
183
118
Dx for PSC?
184
119
Management for PSC?
187
120
Comps of PSC?
190
121
Px for PSC?
191
122
What diseases can lead to cirrhosis (ESLD)?
192
123
Comps of ESLD?
jaundice
palmar erythema
spider angioma
encephalopathy w/ asterixis
portal HTN
Ascites and muscle wasting
Spontaneous bacterial peritonitis
124
What causes hepatic encephalopathy?
portosystemic and hepatocellular dysfunc that leads to increased serum ammonia levels.
Ammonia in a normal liver would have been converted to urea, but in HE crosses into the blood brain barrier.
125
Tx of HE?
aimed at reducing ammonia derived from gut/gut bacteria
Grade I – II: Lactulose 30mL BID or TID with a goal of 2 bowel movements per day and/or Rifaximin 550mg BID
Grade III – IV: in hospital, lactulose 15mL oral or via NG tube q 2hours until patient has BM and mental status improving
126
What causes portal vein thrombosis?
200
127
Dx of portal vein thrombosis? tx?
Doppler US, CT, or MRI
anticoagulation with heparin or low-molecular-weight heparin
128
tx for Fluid Overload: Ascites, LE edema and pleural effusion secondary to ESLD?
1st line: Diuretics: furosemide and spironolactone, usu. at a ratio of 40mg and 100mg respectively
Compression stockings for LE edema
2nd line: paracentesis/thoracentesis
3rd line: Transjugular Intrahepatic Portosystemic Shunt (TIPS)
129
What is spontaneous bacterial peritonitis?
An infection in the abdominal ascites fluid and/or the pleural fluid
130
s/s of spontaneous bacterial peritonitis?
fever, abdominal pain, change in mental status, or asymptomatic
131
Dx of SBP?
204
132
tx of SBP?
204
133
What labs do you want to monitor in a pt with ESLD?
PT-INR, Na, Cr
134
What can be used to determine deg of ESLD?
Model of End-Stage Liver Disease (MELD)
mortality
135
MC risk factor for HCC?
cirrhosis
136
Dx of HCC?
US and/or CT
AFP
Liver biopsy to confirm
137
Tx of HCC?
If cancer is not metastatic and lesion/s are within a certain size criteria can be treated with liver transplant
monitor with alternative CT/MR Q6mo
prevention of growth with TACE
138
What is Cholangiocarcinoma?
CA arising from the bile duct epithelium
139
Epidemiology of Cholangiocarcinoma?
225
140
Etiology of cholangiocarcinoma?
226
141
s/s of cholangiocarcinoma?
Painless jaundice, weight loss, and abdominal pain in patient >55 years old
pruritus, triad of fever/jaundice, RUQ pain
