Liver Disease
Definition:
Liver disease is classified according to the
duration of abnormalities as either acute (< 6 months) or chronic (>6
months). Liver disease is common in the tropics from widespread consumption of
alcohol and since the organ is in effect a filter of blood coming from the
portal circulation, it is far more frequently exposed to bacteria, viruses,
parasites and toxins.
Laboratory Evaluation:
Aminotransferases: (AST, ALT), intracellular enzymes released
secondary to necrosis/inflammation. ALT more specific for liver than is AST
(also found in heart, skeletal muscle). ALT > AST more likely viral
hepatitis or fatty liver. AST: ALT ratio is > 2:1, this is suggestive of
alcoholic hepatitis. Increased LDH is
suggestive of ischemic or toxic hepatitis
Alkaline phosphatase: enzyme bound in hepatic canicular
membrane. Besides liver, found in bone, intestines. Confirm it is liver in
origin by check gamma glutamyltranspeptidase (will also be increased).
Increased levels seen in biliary obstruction or intrahepatic cholestasis.
Albumin: marker for liver protein synthesis. Decreases in chronic
liver disease
Prothrobmin Time (PT): depends on synthesis of
coagulation factors. Increased levels found in severe acute injury or chronic
injury.
Bilirubin: product of heme metabolism in liver. Direct or conjugated
bilirubin is increased in obstruction.
Imaging:
Abdominal ultrasound: important for assessing portal and
hepatic veins, degree of injury
Patterns of Liver Injury
Hepatocellular: marked
increase in AST and ALT +/- increased bilirubin in severe forms. AST and
ALT > 1,000 is indicative of severe viral hepatitis, acetominophen toxicity
or ischemic hepatitis
Cholestasis:
increased alkaline phosphatase and direct bilirubin +/- mild increases in AST
and ALT
Jaundice: a clinical sign when bilirubin levels are
high > 2.5 mg/dl, if hyperbilirubinemia is conjugated, should see increase
in urine bilirubin
Fulminant liver failure:
increases in AST/ALT and alkaline phosphtase/bilirubin, need to also see
increased in PT/INR and hepatic encephalopathy
Clinical Presenation:
Jaundice and/or
hepatomegaly are almost always encountered with liver disease.
Other signs of liver
disease: clubbing, palmer erythema, bruising, asterixis, spider nevi, gynecomastia,
loss of body hair, splenomegaly, ascites, testicular atrophy, edema, muscle
wasting
Types of Liver Injury:
Prehepatic causes:
Falciparm
malaria, HUS, sepsis, pneumococcal pneumonia, sickle cell disease
Hepatic causes:
Viral Hepatitis: acute clinical syndrome
ranges from asymptomatic infection to fulminant liver failure. Some progress to
subclinical persistent infections and progress to chronic liver disease with
cirrhosis +/- hepatocellular carcinoma.
-Pathophysiology: panlobular infiltration with
mononuclear cells, hepatic cell necrosis, variable degress of cholestasis
-Signs/symptoms: anorexia, malaise, nausea,
vomiting, fatigue, myalgias, headache, low grade fevers, RUQ pain, jaundice in
2 weeks, dark urine/pale stools. Increased AST/ALT first, bilirubin rises later
in disease course. Prolonged PT = severe disease.
-Hepatitis
A: fecal oral transmission, serologies: acutely
anti HAV IgM, past infection is IgG. Can be a mild illness in children. No
chronic carrier state. Treatment is supportive.
-Hepatitis
B: **most common in tanzania, parenteral and
perinatal -transmission.
-Serologies: hep B surface antigen positive =
infection. Hep B surface antibody positive: immune to infection. Hep B E
antigen positive: high infectivity rate.
-Pathophysiology: liver damage is mediated by host
cellular immune response to infected hepatocytes
-Hep B infected patients have a high rate of
progression to hepatoma (cancer). -Treatment: supportive, interferon,
lamivudine, adefovir, tenofovir
-Can have co-infection with Hep D (hep D needs hep
B in order for infection)
-Hepatitis
C: parenteral transmission (particularly IV drug
abuse). Serology: anti Hep C antibody positive. Treatment: pegylated
interferon, ribaviron
-Hepatitis
E: fecal oral transmission. More common in
southeast asia. Increased mortality in pregnancy. Serology: IgM anti HEV
-EBV, CMV can also cause viral hepatitis
Alcoholic Hepatitis: usually an acute
exacerbation of symptoms in a patient with chronic and excessive alchohol
ingestion.
-Pathophysiology: hepatocyte injury,
necrosis, polymorphonuclear infiltration
-Signs/Symptoms: RUQ pain, nausea, vomiting, low
grade fever, jaundice, leukocytosis, AST: ALT ratio > 2:1, tender
hepatomegaly
-Treatment: stop alcohol, supportive. If severe
injury with hepatic encephalopathy, can treat with steroids x 1 month with
taper
Vascular Hepatitis:
-Ischemic hepatitis: “shock liver” from severe
hypotension (low cardiac output state) from septic shock, cardiogenic shock,
AST/ALT > 1000
-Congestive hepatitis: from any cause of right
sided heart failure -> passive congestion leading to ischemia and necrosis
of liver
-Budd-Chiari Syndrome: occlusion (thrombosis) of
the hepatic veins leading to sinusoidal congestion and portal hypertension
-> passive congestion and ischemia of liver, necrosis of hepatocytes
Toxin induced Hepatitis:
-Acetominophen: usually ingestion > 10 grams to
cause clinical syndrome but can occur at 2-6 grams in malnourished and
alcoholics. 4-12 hours after ingestion: nausea, vomiting,diarrhea, abdominal
pain, shock. Treatment: n-acetylcysteine
-Isoniazid, rifampin, fluconazole, phenytoin
-HIV medications: zidovudine, didanosine,
nevirapine
-All statins for hyperlipidemia (stop drug is
AST/ALT reaches 3-4 x upper limit)
Autoimmune Hepatitis:
-Pathophysiology:
cell mediated immunological attack on liver cells
-Type 1: most common
-Signs/Symptoms:. Nausea/vomiting, fatigue,
arthritis, anorexia, rashes, anemia.
-serology: anti smooth muscle antibody, + ANA.
Treatment: steroids
Genetic Causes of Liver disease:
-Hemochromatosis: iron overload with deposition in
liver, heart, pancreas. Signs/symptoms: bronze skin coloring, arthritis, CCF,
hepatomegaly, cirrhosis. Diagnosis: increased iron saturation (iron/TIBC x 100%
> 45%), increased ferriton.
-Wilson’s Disease: copper overload. Signs/symptoms:
neurological manifestatinos (copper toxicity in brain), movement disorder, psychiatric,
Kayser-Fleischer rings (copper deposits in cornea). Diagnosis: low serum
ceruloplasmin.
Biliary origin:
-Primary biliary
cirrhosis: autoimmune destruction of intrahepatic ducts
-Primary sclerosing cholangitis: cholestasis
with fibrosis, stricturing of intra and extra hepatic ducts
Liver Disease Clinical Cases
Case 1
38 yo male with no past medical history presents to hospital with 2
week history of malaise, fatigue, nausea, RUQ pain and a 3 day history of dark
urine and pale stools. His blood pressure on admission is 130/80 and heart rate
74. He is afebrile.
1. What disease
process is he describing?
a. Acute
liver injury with hepatic insufficiency
2. What laboratory
tests and/or images do you want to order?
a. LFTs, US abdomen, EtOH level, Hepatitis
Panel, Coags, FBP
3. What kinds of
questions do you want to ask him to get a better history?
a. Recent
exposures, etoh history, meds, sick contacts, new foods, contact with lake
victoria
You order liver function tests and an abdominal ultrasound. His AST/ALT
come back moderately high and his bilirubin is mildly high. Ultrasound is still
pending. His RUQ pain is dull, achy and does not radiate. He does tell you that
he is regularly involved with prostitutes. He does not drink alcohol
excessively and he does not take any medications.
1. What is the most
likely etiology of his liver disease?
a. Hepatitis B
2. What serologies do
you want to order and which ones may come back positive?
a. Hepatitis panel with HbsAg, HbsAb, HBcAb,
HBeAb specifically
i.
Would
also want to know IDS status!
3. What treatment can
you offer him?
a. Oral therapy is thought to be as effective as
Ifn, without the often intolerable side effects, So could start with lamivudine, adefovir, or
tenofovir.
Case 2
40 yo male who is HIV positive (CD4 count of 300) presents with 2 month
history of abdominal pain, nausea, vomiting and fatigue. He just started his
antiretrovirals about 6 months ago and takes them daily. His abdominal pain is described as RUQ and
dull with no radiation. He has not noticed any discoloration of his skin, urine
or stool. His blood pressure on admission is 120/78 and his heart rate is 72.
He is afebrile.
1. What laboratory
tests and/or imaging do you want to order?
a. LFTs, US abdomen, EtOH level, Hepatitis
Panel, Coags, FBP
2. What are you
looking for in those laboratory tests?
a. Transaminase pattern and level, coagulopathy,
liver texture, hepatitis serologies, and for signs of thrombocytopenia/anemia
3. What other
questions do you want to ask?
a. Beyond the things mentioned above, with this
patient on ARVs knowing which medications is quite important!
You order liver function tests and an abdominal ultrasound. The tests
come back showing an elevated AST and ALT but normal alkaline phosphatase and
bilirubin. His abdominal ultrasound shows patent hepatic and portal veins and
mild hepatomegaly, no splenomegaly. His portal pressure on the abdominal
ultrasound is normal. He tells you that his medications include nevirapine
1. What is the most
likely etiology of his liver disease?
a. Acute hepatocellular damage 2/2 nevirapine.
2. How to do you want
to treat this patient?
a. Change ARV regimen!
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