CPD II: liver

here is the section in the GI notes on liver diagnosis that i missed when we were in the thick of the semester...

liver dysfunction can manifest in many different body systems: liver failure or cirrhosis might cause generalized fatigue / anorexia / weight loss. an infection or inflammation of the liver might cause a fever. bad breath might result from abnormal methionine metabolism in late cirrhosis. bilirubin backup can appear as jaundice, or even pruritis. increased serum lipids might lead to xanthomas and xanthelasmas. improper estrogen / androgen metabolism might result in gynecomastia and testicular atrophy, as well as spider telangiectasias.

fatty liver is a fairly common dysfunction of the liver that afflicts about 25-30% of the population. it results from abnormal accumulation of fat droplets within the liver, which can ultimately lead to fibrosis, scarring, and cirrhosis. it is not directly caused by fatty food intake- other risk factors include diabetes and alcoholism. clinically, it might present as liver enlargement and slight elevation of liver enzymes. if steatosis progresses to fibrosis (and if alcohol is not involved), then non alcoholic steatohepatitis develops. this is more likely to occur in middle aged, obese, diabetic women who are on hormone therapy such as synthetic estrogen. like simple fatty liver, it might present simply as an enlarged liver and slightly elevated liver enzymes with no other symptoms, or might present with increased BP, palmar erythema, muscle aches/fatigue, muddy sclera.

hepatitis is inflammation and necrosis of the liver and infectious hepatitis can occur in several different flavors, hep A through E mostly. these all present with similar symptoms, including flu like symptoms, jaundice, RUQ pain, and have similar stages of development which include a prodromal phase with generalized symptoms. each variant has a particular mode of transmission: A and E are mostly via fecal oral, or oral/anal sexual practices. B and D are via unprotected sex or contaminated syringes, and C is mainly from contaminated syringes. all forms might present with an enlarged, tender liver and may have splenomegaly as well. labs that might aid in diagnosis: high ALT / AST, bilirubin, low albumin / platelets, normal WBC.

prolonged acute hepatitis can result in chronic inflammation which might lead to chronic hepatitis, which can come in several varities: lobular, persistent, and active (most likely to lead to failure/cirrhosis). presentation can be similar to acute, or nonspecific, or lupoid like symptoms. lab findings might be similar, with high ALT / AST, bilirubin, prolonged PT, decreased albumin, hyperglobulinemia, and presence of ANA in lupoid presenting patients. diagnosis is by liver biopsy and differential should consider wilson's disease if serum copper is elevated.

fulminant hepatic failure is defined as a combination of acute liver failure and encephalopathy that develops in less than 8 months with no prior history of liver dysfunction. it can be caused by a number of factors such as viruses, fatty liver, ischemia, toxin buildup. it might develop into coma, hypoglycemia, cerebral or GI hemorrhage, renal insufficiency-- despite this, the long term prognosis is excellent.

cirrhosis of the liver occurs after longstanding injury or inflammation of the liver from a variety of causes and is a combination of fibrosis, necrosis, regeneration, ultimately resulting in hepatocyte shrinking. it is most commonly caused by hep C, then alcoholism, then hep B and cryptogenic causes. if it is due to alcohol, the liver might feel both enlarged and with a bumpy edge. cirrhosis can present with clubbing, dupuytren's contracture, fetor hepaticus, pleural effusion, and dilated abdominal veins. additionally, because of restricted blood flow, it results in portal hypertension and can cause ascites and esophageal varices.

cirrhosis predisposes to formation of liver cancer, hepatocellular carcinoma. HCC can also be related to chronic alcoholism, childhood hep B infection, hep C (especially in japan and europe), HBV, hemocromatosis. prognosis is not good; usually leads to death within 6-20 months. it presents similarly to advanced cirrhosis and lab markers such as transaminases, alk phos, bilirubin, LDH are elevated. alpha fetal protein is elevated in 75% of cases and is a good way to predict for HCC.

liver tumors can also be benign, as in the case of hepatic adenoma- which is most commonly seen in women in their 30's on birth control pills. they would present asymptomatically, or with hepatomegaly if the tumor was big enough, or with RUQ pain if ruptured (rare). once oral contraceptives are stopped, prognosis is good.

finally, gilbert's syndrome is an autosomal recessive disorder in which bile pigment clearance from the liver is impaired, resulting in elevated bilirubin levels without outright liver damage. it might be triggered by dehydration, stress, menses, viruses, fasting, and might only present with mild jaundice and vague symptoms like abdominal cramping and fatigue. diagnosis is by excluding hemolysis by testing for normal LDH and CBC reports, and liver tests to confirm that liver function is normal (except for unconjugated bilirubin).

questions
how might the following symptoms be related to liver dysfunction?
1. fatigue / anorexia / malaise / weight loss.
2. fever.
3. fetor hepaticus.
4. spider telangiectasias.
5. jaundice.
6. pruritis.
7. xanthoma / xanthelasma.
8. gynecomastia / testicular atrophy.
9. hypoglycemia.
10. abdominal swelling.
11. behavioral changes.

fatty liver...
12. what are the top 3 causes of chronic liver disease?
13. what percentage of the population does fatty liver affect?
14. describe the general progression of pathogenesis from fatty liver to cirrhosis.
15. what are some etiological factors for fatty liver?
16. what are some diagnostic signs for fatty liver?

NASH...
17. how big a factor does NASH play in chronic liver disease?
18. what is the etiology of NASH?
19. describe the patient type that is at greatest risk for developing NASH.
20. many patients with NASH show an elevation of...
21. what is the clinical picture of a patient with NASH?

acute viral hepatitis...
22. what is hepatitis?
23. what are the four stages of presentation of infectious hepatitis?
24. what are the hallmarks of hep. A signs / symptoms?
25. when is the period of greatest infectivity in hep A and how long does it take for hep A to resolve?
26. what is the risk of complication for hep B and C?
27. Hep D requires...
28. where in the world is hep E most likely to be found?
29. how are hep A and E transmitted?
30. how are hep B and D transmitted?
31. how is hep C transmitted?
32. what are some PE signs for patients with infectious hepatitis?
33. what are some lab findings that can aid in the diagnosis of infectious hepatitis?
34. what are some potential complications of infectious hepatitis?

chronic hepatitis...
35. what is the etiology of chronic hepatitis?
36. what are three types of chronic hepatitis? which is the most serious?
37. what are the signs/symptoms of chronic hepatitis?
28. what are the lab findings expected to be found in chronic hepatitis?
29. if a patient has chronic hepatitis symptoms plus high serum copper, what should be considered as a DDX?
30. what is a way to differentiate between alcoholic and non alcoholic hepatitis by lab tests?

fulminant hepatic failure...
31. what is fulminant hepatic failure?
32. what are some etiologies for fulminant hepatic failure?
33. what are the signs/symptoms of fulminant hepatic failure?
34. what are the complications of fulminant hepatic failure?
35. what is the prognosis of fulminant hepatic failure?

cirrhosis...
36. what is cirrhosis?
37. what are the most common causes of hepatic cirrhosis?
38. what are the two presentations of a patient with hepatic cirrhosis?
39. what might the liver feel like for a patient with cirrhosis due to alcohol?
40. cirrhosis is the most common cause of...
41. why might cirrhosis have normal or low liver enzymes?
42. what markers might be elevated with liver cirrhosis?
43. what are some complications of cirrhosis?
44. what are two other potential causes of cirrhosis?

liver cancer...
45. HCC leads to death in...
46. what are some risk factors for HCC?
47. what is the median age of diagnosis of HCC in the US and europe?
48. how great of a risk factor for HCC is cirrhosis?
49. what percentage of HCC is related to alcohol use?
50. what is the most common cause of HCC in japan and europe?
51. what are the signs and symptoms for liver cancer?
52. what are some lab markers that would be increased in liver cancer?
53. which lab marker is elevated in 75% of HCC cases?

hepatic adenoma...
54. describe the patient type that is most likely to have a hepatic adenoma.
55. what are the signs and symptoms of hepatic adenoma?
56. what is the severity and prognosis of HA's?
57. what is a PE finding that hepatic adenoma might present with?
58. what is a ddx for HA and why?

gilbert's syndrome...
59. what is gilbert's syndrome?
60. how common is gilbert's syndrome?
61. what are the etiologies / triggers of gilbert's syndrome?
62. what is the clinical presentation of gilbert's syndrome patients?
63. what labs are performed to diagnose gilbert's and why?

answers
1. liver failure / cancer / cirrhosis.
2. infectious hepatitis or inflammation.
3. abnormal methionine metabolism; late stage of cirrhosis.
4. altered estrogen / androgen metabolism.
5. elevated bilirubin from decreased ability of liver to metabolize and excrete bilirubin.
6. elevated bilirubin levels again- skin is an elimination pathway.
7. increased serum lipids.
8. improper estrogen / androgen metabolism.
9. impaired gluconeogenesis.
10. ascites from portal hypertension.
11. hepatic encephalopathy.

12. hep C, alcohol, then hep B.
13. 25-30%.
14. fatty deposits in liver cause enlargement, leading to fibrosis and scarring, which eventually leads to cirrhosis.
15. diabetes, poor diet, heavy alcohol use.
16. enlarged liver, slightly elevated liver enzymes. confirmed by liver biopsy.

17. third most common reason for chronic liver failure after hep C and alcoholism.
18. no known specific cause.
19. middle aged, obese, diabetic woman taking hormones but doesn't drink alcohol.
20. ferritin.
21. asymptomatic, or
enlarged liver
palmar erythema
increased systolic BP
muddy sclera
muscle aches / fatigue

22. inflammation of the liver with patched or scattered necrosis affecting all acini.
23. viral replication (asymptomatic), prodrome (generalized symptoms), icteric (jaundice, darkened urine, RUQ pain), convalescence.
24. flu symptoms, abdominal cramps, jaundice.
25. 1-2 days before onset of jaundice, 2 months to resolve.
26. 10% of hep B and 80% of hep C patients can develop longstanding liver inflammation which might result in liver cirrhosis and failure.
27. hep B virus.
28. developing countries, rare in the US.
29. fecal/oral, contaminated food or water. high association with oral / anal sexual practices.
30. unprotected sex, contaminated syringes.
31. mostly contaminated syringes.

32. liver tender and enlarged, may see splenomegaly as well.
33. huge elevations of ALT / AST
hyperbilirubinemia
low platelets, albumin
normal WBC
34. post hepatitis syndrome, cholestatic hepatitis, fulminant hepatitis, chronic hepatitis.

35. all forms of infectious except for A and E.
36. persistent, lobular, active (most serious).
37. asymptomatic or
nonspecific
or present like acute hepatitis
hepatosplenomegaly
jaundice
lupoid symptoms
serious systemic illness symptoms: cutaneous, constitutional symptoms.
28. elevated AST, ALT, bilirubin, prolonged PT, decreased albumin, hyperglobulinemia, ANA.
29. wilson's disease.
30. strikingly high WBC count, and only moderate elevation of AST/ALT in alcoholic hepatitis.

31. liver failure and encephalopathy which develops in less than 8 weeks with no prior history of liver disease.
32. viral, fatty liver, ischemia, toxins.
33. symptoms of encephalopathy
symptoms of acute liver failure
ascites
hypoprothrombinemia
malnutrition.
34. cerebral hemorrhage
coma
hypoglycemia
Gi hemorrhage
renal insufficiency
35. 20% short term, excellent long term.

36. triad of parenchymal necrosis, fibrosis, regeneration from longstanding inflammation or injury.
37. hep C
alcoholism
hep B
"cryptogenic causes"
38. "well compensated"- asymptomatic
"decompensated":
clubbing
Dupuytren's contracture
fetor hepaticus
pleural effusion
dilated abdominal veins
[club dupuy fetor lungs stomach] [club deco- a contract for your feet, lungs, and stomach]
39. enlarged liver with bumpy, nodular edge.
40. ascites.
41. because of the shrinking and loss of functional hepatocytes.
42. bilirubin
transaminases
alk phos
PT
gamma globulin
43. GI hemorrhage
encephalopathy
renal failure
liver cancer
ascites
44. primary biliary cirrhosis, obstructive biliary cirrhosis.

45. 6-20 months.
46. asians, childhood hep B infection, cirrhosis, HBV, hemochromatosis.
47. 65 years old.
48. 80% of patients with HCC have preexisting cirrhosis.
49. 30%.
50. HCV.
51. present similar to advanced cirrhosis:
pruritis
jaundice
splenomegaly
varices
cachexia
ascites
[pj's vac]
52. transaminases
alk phos
bilirubin
LDH
AFP
[taable]
53. AFP.

54. 34 year old female who takes birth control pills.
55. asymptomatic.
56. benign and go away when OCP's halted.
57. RUQ mass or hepatomegaly.
58. cholecystitis because rupture can cause acute RUQ pain.

59. an autosomal recessive disorder that results in defective bile clearance from the liver which causes elevated bilirubin.
60. 3-5% population.
61. dehydration
stress
menstrual periods
viral infection
fasting
62. asymptomatic or nonspecific findings. may have mild jaundice.
63. CBC and LDH to rule out hemolysis, liver enzymes to rule out liver damage.