Download Liver Disease - University of Toledo

Liver Disease
Thomas C Sodeman MD FACP
Associate Professor of Medicine
Chief, Division of Hepatology
University of Toledo
Liver Disease
• Approach to abnormal labs
– AST
– ALT
– Alkaline phosphatase
– Bilirubin
2
Liver Disease
• Laboratory patterns
– Hepatitis
• AST/ALT//Alkaline phosphatase
– Cholestatic
• Bilirubin/alkaline phosphatase//AST/ALT
3
Liver Disease
• Laboratory patterns
– Hepatitis
• AST/ALT < 1000 viral
– Hepatitis
• AST/ALT > 5000 fulminant hepatitis
4
You are seeing a 24 year old male to establish care. He
states he has had no medical issues, but has noticed
his eyes will turn yellow when he has a cold. He is
concerned that he may develop cirrhosis like his father,
who drank heavily. He is on no medications, and his
examination is normal. His total bilirubin is 2.3 mg/dL,
direct bilirubin 0.2 mg/dL. Your next evaluations should
be:
a. Reassurance
b. CT scan of the liver
c. Hepatitis serologies
d. Liver biopsy
e. HFE gene study
5
Liver Disease
• Hyperbilirubinemia
– Unconjugated – increased production
• Hemolysis
– Conjugated - dysfunction
– Gilbert’s syndrome
– Elevated total bilirubin – unconjugated
– Fasting / illness
6
You are asked to see a 67 year old male found at home
and hospitalized. He has a past history of hypertension
and dementia. His diet recently had consisted of only
prune juice and celery. He is disheveled looking,
emaciated, and has multiple bruises on his upper and
lower extremities. His labs show an albumen of 1.3,
normal transaminases, a microcytic anemia, and an
INR of 2.5. He takes no medications at home. Your
next step to evaluate his elevated INR would be:
a. Hepatitis serologies
b. Ceruloplasmin
c. Ultrasound of the liver
d. Vitamin K supplementation
e. Liver biopsy
7
Liver Disease
• Measures of synthetic function
– Short term
• PT/INR
– Longer term
• Albumen
8
Liver Disease
• Measures of synthetic function
– INR elevation due to malabsorption vs.
dysfunction
– Malabsorption responds to vitamin K
9
Liver Disease
• Other evaluations
– Radiologic
– Pathologic
– Functional
• HIDA
10
Liver Disease
• Radiologic
– Ultrasound – masses, flow, fat
– CT – masses, fat
– MR – masses, fat
– PET – malignancy
– ERCP – ‘plumbing’
11
Liver Disease
• Pathologic
– Diagnosis – used when labs / imaging unclear
– Staging – degree of fibrosis – important for
treatment decisions and prognosis
12
Your patient, a 25 year old female, just returned from a
vacation in Mexico a month ago. Recently she has
been feeling fatigued, and has had modest right upper
quadrant discomfort. Yesterday she noticed that her
eyes were yellow. Past medical history is significant for
asthma, current medication is an inhaler. Physical
exam reveals scleral icterus, and a slightly enlarged
liver. Laboratories show an INR of 1.0, AST 450 U/L,
ALT 435 U/L, and bilirubin of 3.2 mg/dL. Your next
evaluation would be:
a. Intravenous immunoglobulin
b. Referral for liver transplantation
c. Referral for alcohol treatment
d. Lamivudine 100mg po QD
e. HAV IgM
13
Liver Disease
• Hepatitis A
– Incubation 2-6 weeks
– Fecal oral
– IgM anti HAV
– No treatment
– No chronic condition
– Ig for contacts
– Vaccine for travelers
14
Your patient comes in with jaundice. He is a 30 year old
male with a history of intravenous drug abuse. He has
not recently traveled, and drinks 2 to 3 beers a day. On
examination he has scleral icterus and jaundice, no
asterixis, no ascites or edema, and no stigmata of
chronic liver disease. Past screening has been
negative for viral hepatitis, and past medical history is
unremarkable. Labs show as AST of 1000 U/L, ALT
1200 U/L, alkaline phosphatase of 150 U/L, total
bilirubin of 3.0 mg/DL, and an INR of 1.2. Your next
step should be:
a. Referral for liver transplantation
b. CT scan of the liver
c. Hepatitis serologies
d. Liver biopsy
e. Lamivudine 100 mg PO QD
15
Liver Disease
• Hepatitis B
– Incubation 4 – 24 weeks
– Parenteral
– HBsAg, HBsAb
– HB core Ab
– HB e Ag, Ab
– HBV DNA
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Liver Disease
HBsAg
Anti HBs
IgM anti
HBc
IgG anti
HBc
HBeAg
Anti HBe
DNA
+
-
+
-
+
-
+
Acute
-
+
-
+
-
-/+
-
Immune
-
+
-
-
-
-
-
Vaccinated
+
-
-
+
-
+
<105/mL
Carrier
+
-
-
+
+
-
>105/mL
Chronic
replicating
17
Your patient comes for evaluation of her chronic hepatitis.
She is a 53 year old nurse who contracted hepatitis B
via a needle stick. She does not drink alcohol, and has
well controlled hypertension. Examination is normal,
labs show AST and ALT twice normal, and HBV DNA
PCR shows 1,300,000 copies / mL. Liver biopsy
showed minimal fibrosis and moderate portal and
parenchymal inflammation. Your next step would be:
a. Reassurance
b. CT scan of the liver
c. Referral for liver transplantation
d. Tenofovir
e. Repeat liver biopsy in one year
18
Liver Disease
• Hepatitis B
– Fulminant
• Initial or reactivation
– Chronic
• Cirrhosis
• Hepatocellular carcinoma
19
Liver Disease
• Hepatitis B
– Treatment
• Evidence of inflammation (biopsy, enzymes)
• Elevated DNA (<10000 copies / mL)
20
Liver Disease
• Hepatitis B
– Treatment
•
•
•
•
Interferon – not in cirrhosis
Lamivudine - resistance
Adefovir
Entecavir
21
Your patient presents for further evaluation of hepatitis C
found at blood donation. He is a 54 year old male in
otherwise good health, and his route of acquisition is a
transfusion at age 10. His examination is normal, labs
show AST and ALT 1.5 times normal, genotype of 1a,
and a viral load of 2,300,000 IU/mL. Testing at
donation showed a viral level of 1,400,000 IU/mL 4
months ago. Your next step is:
a. Pegylated interferon and ribavirin
b. CT scan of the liver
c. reassurance
d. Liver biopsy
e. HFE gene study
22
Liver Disease
• Hepatitis C
– Incubation 2-10 weeks
– Parenteral
– Pre late 1980’s – transfusion / IVDU
– Now - IVDU
23
Liver Disease
• Hepatitis C
– Diagnosis
•
•
•
•
Initial – anti HCV
Confirmation – RNA PCR – not RIBA
Additional – genotype, viral load
Biopsy – long duration, duration unknown,
confounding factors (alcohol)
24
Liver Disease
• Hepatitis C
– Treatment
• Stage ≥2
• Not viral load
– Interferon / ribavirin
• Length depends upon genotype
– 1 – 48 weeks
– 2,3 – 24 weeks
25
Liver Disease
• Hepatitis C
– Treatment
• Side effects
–
–
–
–
–
–
–
Depression – (suicide)
Fatigue
Aches
Cytopenias (RBC / WBC / plt)
Thyroid
Hair loss
Weight loss
26
Liver Disease
• Hepatitis C
– Treatment
• Reasons to stop treatment
–
–
–
–
Suicidal ideation
No response at 3 months (2 log drop viral load)
Intolerance of side effects
Not cytopenias unless severe
» First try growth agents
» PLT < 10,000
» ANC <750
» Severe anemia
27
Liver Disease
• Hepatitis D
– Incubation 4-24 weeks
– Parenteral - IVDU
– Coinfection
– Superinfection
– Treat HBV
28
Liver Disease
• Hepatitis E
– Incubation 2 – 9 weeks
– Parenteral
– Rare in US
– Similar to HAV
– 20% mortality in pregnancy
29
Liver Disease
•
•
•
•
CMV
EBV
HZV - pregnancy
Adenovirus
30
Your patient presents for evaluation of fatigue, She is a 65
year old retired teacher with a past medical history of
hypothyroidism and hypertension, under control.
Examination reveals slight hepatomegaly and 1+
pitting edema at the ankles. Laboratories show AST
and ALT 1.5 times normal, normal bilirubin and alkaline
phosphatase, and a normal CBC. Your next step is:
a. Reassurance
b. CT scan of the liver
c. Hepatitis serologies
d. ANA and serum protein electrophoresis
e. Alcohol counseling
31
Liver Disease
• Autoimmune hepatitis
– Distribution 3:1 F:M
– Peaks 10-20 years, 50 years
– Presentation
• Chronic
• Fulminant
– 1/3 with another autoimmune disorder
32
Liver Disease
• Autoimmune hepatitis
– Fatigue
– Jaundice
– Anorexia
– Myalgia
33
Liver Disease
• Autoimmune hepatitis
– Ast Alt ≈ 500 (>1000)
– ANA >1:80
– ASMA > 1:80
– LKM1 >1:80
– Gamma globulin > 1.5x normal
34
Liver Disease
• Autoimmune hepatitis
– Biopsy
– Interface hepatitis
– Plasma cells
35
Liver Disease
• Autoimmune hepatitis
– Treatment
• Prednisone / imuran
–
–
–
–
80% remission
2 years
Relapse in 50%
Retreat relapsers
• 90% mortality untreated
36
Your patient, a 58 year old woman, presents with one
month of pruritus. She has no significant past medical
or exposure history, no recent travel or new pets.
Examination shows xanthomas and excoriations, and
otherwise is normal. Labs show AST and ALT twice
normal, and alkaline phosphatase of 450 U/L, total
bilirubin of 1.2 mg/dL. The your next step should be:
a. Reassurance
b. CT scan of the liver
c. Hepatitis serologies
d. Liver biopsy
e. Anti mitochondrial antibody
37
Liver Disease
• Primary biliary cirrhosis
– Small bile duct
– 9:1 M:F
– Age 40-60
– Elevated alkaline phosphatase
– Pruritus / fatigue
– AMA > 1:40
– Ursodeoxycholic acid 12 -15 mg/kg
– Osteoporosis
38
Your patient, a 24 year old male with a 10 year history of
ulcerative colitis, presents for a routine evaluation. His
colitis has been under control with Asacol, and he has
no other significant medical issues. Examination is
unremarkable. Laboratories show AST and ALT twice
normal, Alkaline phosphatase 450, total bilirubin of 1.4
mg/dL, and a normal CBC. Your next step is:
a. Reassurance
b. CT scan of the liver
c. Hepatitis serologies
d. ERCP
e. Liver biopsy
39
Liver Disease
• Primary sclerosing cholangitis
– Medium and large duct disease
– 80% associated with ulcerative colitis
– Increased alkaline phosphatase
– Dominant strictures
– Cholangiocarcinoma / colon ca
– Osteoporosis
– No effective treatment
40
Your patient presents for routine follow up. He is a 53 year
old lawyer with a past medical history of hypertension,
elevated cholesterol and type 2 diabetes. He is on
therapy for all three diseases. Examination is normal
except for obesity. Labs show a normal AST, ALT of 60
U/L, normal alkaline phosphatase and bilirubin.
Previous labs have been normal. Your next step
should be:
a. Reassurance
b. CT scan of the liver
c. Hepatitis serologies
d. Liver biopsy
e. Repeat labs in 3 months
41
Liver Disease
• NASH
– Fatty liver – cirrhosis
– Obesity
– DM
– Hyperlipidemia
– TPN
– ALT>AST <200
– Diagnosis of exclusion
42
Liver Disease
• NASH
– Treatment
•
•
•
•
Weight loss
Control of diabetes / lipids
Gastric bypass
PPAR-g agents
43
Liver Disease
• Alcoholic liver disease
– Alcoholic liver disease
• 80 g / d men
• 40 g / d women
• AST 2x ALT <300
44
Liver Disease
• Alcoholic liver disease
– Alcoholic hepatitis
•
•
•
•
•
Elevated AST>ALT bilirubin INR WBC
Discriminant function >35
4.6[Pt-Ptcontrol] + bil (mg/dL)
Neutrophils on biopsy
Treatment
– Prednisone / pentoxyphylline / TNF a agents
45
You are seeing a new patient, a 35 year old male. He
complains of some fatigue, but otherwise is in good
health. Examination is normal. His family history
includes cirrhosis in an uncle and CAD. Labs show
normal liver enzymes, a ferritin of 750 mg/L, and iron
saturation of 88%. Your next step is:
a. Reassurance
b. CT scan of the liver
c. HFE gene study
d. Hepatitis serologies
e. Liver biopsy with quantitative iron level
46
Liver Disease
• Hereditary Hemochromatosis
– Most common inherited disorder in Europeans
– C282Y
H63D
– Autosomal recessive
– Ferritin elevation
• 400
– Iron saturation
• 50%
47
Liver Disease
• Hereditary Hemochromatosis
– Diabetes
– Cardiomyopathy
– Arthritis PIP/DIP
48
Liver Disease
• Hereditary Hemochromatosis
– Ferritin > 1000 / elevated AST – biopsy
– No role for iron index
49
Your patient , a 35 year old male with hereditary
hemochromatosis (C282Y/C282Y) presents asking
about therapeutic options. His labs showed AST and
ALT twice normal, ferritin of 1300 mg/L, iron saturation
of 92%. Liver biopsy showed minimally increased
fibrosis. Your next step is:
a. Reassurance
b. Chelation with desferroximine
c. Weekly therapeutic phlebotomy
d. Low iron diet and observation
e. Penicillamine therapy
50
Liver Disease
• Hereditary Hemochromatosis
– Phlebotomy
• Initially weekly
– Ferritin<50
• Q three months
51
You are seeing a 22 year old female in the hospital for
elevated liver enzymes. She was hospitalized for acute
psychosis a week earlier. On examination she has
choreaform movements of her hands, and otherwise
examination is normal. Labs show AST and ALT twice
normal, an alkaline phosphatase of 50 U/L, and is
otherwise normal. Your next step is:
a. No further testing
b. Serum ceruloplasmin
c. Spot urine copper
d. Liver biopsy
e. Hepatitis serologies
52
Liver Disease
• Wilson’s disease
– Age 15-40
• Acute – fulminant failure
– Hemolytic anemia
•
•
•
•
Chronic – cirrhosis
Ceruloplasmin <20 mg/dL
24 hour urine copper >80 mg/24h (>250)
Psychiatric symptoms
53
Liver Disease
• Wilson’s disease
– ATPB7
• Treatment
– Penicillamine
– Trientine
lifetime
– Zinc
– Transplant – FHF, cirrhosis
• curative
54
Liver Disease
• Alpha-1 antitrypsin
– Phenotype
– ZZ
– SS
– SZ
– MZ
– MM
– Null / null
55
Liver Disease
• Alpha -1 antitrypsin
– Variable presentation
– Cirrhosis
– Emphysema
– Neither
– HCC
56
Liver Disease
• Storage diseases
– Amyloid
– Glycogen storage
– Lipopolysaccharidoses
57
Liver Disease
• Liver masses
– Benign
• Usually asymptomatic unless very large
• Found incidentally
– Malignant
• Metastatic / primary
• Primary more likely with cirrhosis
58
You are seeing your patient in follow up for an abnormal
CT. She is 45 and had a CT in the emergency room for
nephrolithiasis, which has resolved. She has no
significant past medical history, and is on no
medications. Repeat CT with contrast shows a 2cm
mass with peripheral enhancement in the left lobe, and
a 3cm mass in the right, also with the same
enhancement. Your next step is:
a. Reassurance
b. CT guided liver biopsy
c. Serum E. histolytica antibodies
d. Referral for surgery
e. Serum alpha fetoprotein
59
Liver Disease
• Liver masses
– Benign - CT
• Adenoma – OCP / hormones
– Irregular enhancement
• Hemangioma – most common
– Peripheral enhancement
• Focal nodular hyperplasia
– Central scar
• Cysts
– Hypodense
60
Your patient presents for follow up of an abnormal CT scan.
He is a 54 year old with a history of alcoholic cirrhosis,
complicated by ascites and modest encephalopathy.
CT showed a 3cm mass in the right lobe with arterial
enhancement, and nodularity of the liver consistent
with cirrhosis. INR is 2.2, bilirubin is 3.1 mg/dL, and
ascites was present. Your next step is:
a. Referral for hospice
b. CT guided liver biopsy of the mass
c. Referral for systemic chemotherapy
d. Referral for liver transplantation
e. Referral for surgical removal of mass
61
Liver Disease
• Liver masses
– Malignant
• Metastatic
• Hepatocellular carcinoma
– Arterial phase enhancement
– Underlying disease
• Cholangiocarcinoma
62
Liver Disease
• Liver masses
– Abscesses
• Amoebic
– Often not associated with colitis
– Metronidazole
• Pyogenic
– Diverticulitis
– Non-enhancing
– Drainage
63
Liver Disease
• Drug hepatotoxicity
– Acute
– Chronic
– Idiopathic
64
Liver Disease
• Drug hepatotoxicity
– Acute
– Chronic
– Idiopathic
65
Liver Disease
• Drug hepatotoxicity
– Acute
•
•
•
•
•
•
•
•
Acetaminophen
Isoniazid
Dantrolene
Nitrofurantoin
Sulfonamides
Phenytoin
Disulfiram
Ketoconazole
66
Liver Disease
• Drug hepatotoxicity
– Chronic
•
•
•
•
•
Nitrofurantoin
Etretinate
Diclofenac
Minocycline
Trazadone
67
Liver Disease
• Drug hepatotoxicity
– Chronic
– Granulomatous – alkaline phosphatase
•
•
•
•
Allopurinol
Carbamazepine
Hydralazine
Quinidine
68
Liver Disease
• Fulminant failure
– Acute liver failure (jaundice, INR)
– Encephalopathy
– No pre-existing liver disease
69
Liver Disease
• Fulminant failure
– Acetaminophen
• 24 hour nomogram
• Mucomyst
– Viral
• HAV, HBV
– Ischemic
– Wilson’s
70
Liver Disease
• Cirrhosis
– Encephalopathy
– Ascites
– Varices
– Hepatorenal syndrome
– Hepatocellular carcinoma
– Transplant
71
Your patient present for follow up She is a 45 year old with
a history of cirrhosis secondary to alcohol and hepatitis
C. her manifestations have included ascites, treated
with furosemide and aldactone, and encephalopathy,
treated with lactulose. She denies any forgetfulness as
does her husband. Her labs show an ammonia of 120
mg/dL, up from 98 mg/dL last month. Your next step is:
a. Reassurance
b. Increase lactulose
c. Add oral neomycin
d. Restrict dietary protein
e. Increase diuretics
72
Liver Disease
• Encephalopathy
– Elevated ammonia
– Predisposing factors
•
•
•
•
Bleeding
Diet
Constipation
Infection
73
Liver Disease
• Encephalopathy
– Treatment
•
•
•
•
•
Lactulose - compliance
Neomycin – ototoxicity
Flagyl
Xifaxin
Zinc
74
Liver Disease
• Varices
– Esophageal
– Gastric
– Rectal
– Screening
• Dx of cirrhosis
• Grade 1-2 – repeat 1-2 years
• Grade 3-4 – banding / b blockers
75
You are seeing a patient in the emergency room. He is a 28
year old with a history of excessive alcohol intake for
12 years. He presented with large volume emesis of
bright red blood. His hemoglobin is 6.2 g/dL, INR 3.4,
platelets 22,000 / mL. A central line has been placed,
fluid resuscitation has been started, and the
gastroenterologist has been called. Your next step is:
a. Placement of a Sengstaken-Blakemore tube
b. Endotracheal intubation
c. Platelet transfusion
d. Fresh frozen plasma
e. Emergent TIPS placement
76
Liver Disease
• Varices
– Active bleeding
– Treatment
•
•
•
•
•
•
•
Intubation
Transfusion to Hb 8
Banding
Sclerosis
Sengstaken Blakemore
TIPS
Surgical shunt
77
Liver Disease
• Portal hypertensive gastropathy
– Iron deficiency anemia
– Responds to b-blockers
78
You are seeing a 46 year old in follow up. She has cirrhosis
secondary to autoimmune hepatitis, and has recently
developed lower extremity edema and non-tense
ascites. Examination is otherwise unremarkable, and
labs show a creatinine of 1.0 mg/dL, and an albumen
of 2.1 g/dL. She is currently on furosemide 20 mg/day.
Your next step is:
a. Change to aldactone 100 mg / day
b. Salt restriction to 500 mg / day
c. Fluid restriction to 1 liter / day
d. Increase furosemide to 40 mg / day and add aldactone
100 mg / day
e. Albumen infusion
79
Liver Disease
• Ascites
– Decreased albumen – oncotic pressure
– Increased portal pressure
– Increased splanchnic blood flow
– Increased water retention due to activation of
renin / angiotensin / aldosterone axis
80
Liver Disease
• Ascites
– Initial evaluation
• Hepatic vs cardiac
• Tap
–
–
–
–
–
OK if INR up / plt down
SAAG
Cell Count
Culture
? cytology
81
Liver Disease
• Ascites
– Treatment
– Aldactone 100 mg/day
– Lasix 40 mg / day
– Max 400 / 160
– Sodium / water restrictions
82
Liver Disease
• Ascites
– Tap – risk of HRS – replace albumen 8g/L
– Indications for repeat taps
• ? Infection
• Diuretic resistance
– TIPS
• Diuretic resistance
– Denver shunt
83
Liver Disease
• Spontaneous bacterial peritonitis
– Often asymptomatic
– Monobacterial
– Ascitic fluid cell count / culture
• > 250 PMN
– Inpatient – cefotaxime
– Outpatient - quinolone
– Prophylaxis – after one episode
• Weekly quinolone
84
Liver Disease
• Hepatorenal syndrome
– Renal vasoconstriction
– Cr > 1.5 mg/dL or CrCl <40 mL/min
– Urine protein <500 mg/d
– No shock
– No renal parenchymal disease
– No improvement after stopping diuretics /
1.5 L NS challenge
85
Liver Disease
• Hepatorenal syndrome
– Indication for transplant
– TIPS
86
Liver Disease
• Hepatocellular carcinoma
– Rare in no liver disease
– Often asymptomatic
• Pain, weight loss, fever
– Worse risk
• Hemochromatosis , α1AT, HBV
– Alpha fetoprotein – Q six months
• <100
• Trend
• >500
– Scans Q six months
87
Your patient presents for follow up. She is 54, and has a
history of cirrhosis secondary to hepatitis C, which has
not been treated yet. She has no encephalopathy or
ascites, and other than fatigue feels well. Labs show
an INR of 1.1, bilirubin of 1.2 mg/dL, platelets of
98,000 / mL, creatinine of 1.1 mg/dL, and a viral load
of 1,300,000 IU/mL. Endoscopy recently shoed no
esophageal varices. She is concerned about getting on
a transplant list. Your next step is:
a. Reassurance
b. Referral for transplantation
c. Referral for liver biopsy
d. Referral for hospice
88
Liver Disease
• Liver transplantation
– Indication
• Dysfunction
• Hepatocellular carcinoma
• Storage / metabolic problems
– MELD score
•5
– normal
• 5-15 – below listing
• >15 – listable
89
Liver Disease
• Liver transplantation
– Contraindications
•
•
•
•
•
Active infection
Extrahepatic malignancy
HIV
Severe extrahepatic diseases – CAD, COPD
noncompliance
90
Liver Disease
• Liver transplantation
– Post transplant issues
•
•
•
•
Diabetes
Hypertension
Renal insufficiency
Recurrence of disease
– HCV/PBC/PSC/AIH
• Rejection
• Plumbing - anastamoses
• Malignancy - skin
91
Liver Disease
• Vaccination
– HBV
• Health care workers, jail, sewer, military
• Children
– HAV
• Travel to endemic areas
– Underlying liver disease
• Recommended in all
92