Liver

Question 1

What is a splenomegaly?

Answer 1

enlargement of the spleen due to an increased resistance to blood flow in the liver, causing higher pressure in the portal venous system.

Question 2

What is acanthosis nigricans?

Answer 2

A velvety discoloration of body creases and folds

Question 3

What tissues are associated with AST (SGOT) liver enzymes?

Answer 3

Liver, skeletal muscle, cardiac muscle and kidney

Question 4

What tissues are associated with ALT (SGPT) liver enzymes?

Answer 4

Only the liver = high levels mean liver cell injury

Question 5

What enzymes are used to detect liver bile duct damage?

Answer 5

Cholestatic enzymes! They indicate disease to biliary system.

Question 6

What are examples of cholestatic enzymes used to detect liver bile duct damage?

Answer 6

Alkaline phosphatase: enzyme from bile ducts, placenta and bone turnover = don’t use this value to evaluate bile duct condition in kids (high bone turnover) or pregnant women

Gamma-glutamyl transferase: only high if liver damage (better detection in all kinds of patients). GGT can be high after having a lomft to drink due to alcohol-induced liver inflammation → very sensitive enzyme

Question 7

What are the different clin presentations of liver damage/disease?

Answer 7

First-time elevations = may be acute injury such as hepatitis A or alcohol-induced liver enzymes

Acute hepatitis = A or E, which is the inflammation of hepatocytes

Chronic hepatitis = B or C

Cholestasis = blockage of bile ducts (large and small)

Cirrhosis = liver inflammation, not always due to alcohol, fat accumulation or chronic hepatitis

Jaundice = accumulation of bilirubin causing yellowing of eyes

Question 8

What might be the cause of bruising and deteriorating eyesight associated with the liver?

Answer 8

Both vitamin A and K are fat soluble vitamins, which respectively play a role in vision and bruising. The digestion of fat requires bile from the gallbladder, so if these vitamins aren’t properly absorbed, there might be a problem with the bile duct (blockage), causing low secretion of bile. This is usually characterized with elevated ALT (due to blockage, will have liver cell damage) and really high ALP levels (due to the blockage of bile ducts).

Question 9

What is the difference between bilirubin and direct-bilirubin?

Answer 9

High levels of bilirubin are usually due to a high rate of RBC breakdown (breakdown of heme). Direct-bilirubin levels that are elevated indicate that the liver is having problems secreting the conjugated (direct) bilirubin, which could cause liver problems if accumulated in high amounts in the liver.

Question 10

What is INR and what does it indicate?

Answer 10

INR (or International Normalized Ratio) is an indicator of how much your blood will clot. The higher the number, the thinner the blood, so the more time it will take for the blood to clot. Vitamin K is used to make blood clotting factors in the liver.

Question 11

What is severe acute hepatitis?

Answer 11

It is when liver functions aren’t working properly, such as making blood clotting factors and having an elevated INR, this causes the patient to die quickly.

Question 12

What are the clinical features of acute hepatitis?

Answer 12

→ can improve on its own

• Symptoms: fatigue, anorexia, nausea, jaundice
• ALT elevation: >10-fold
• Prognosis: usually self-limited
• Treatment: supportive

Question 13

What are the clinical features of chronic hepatitis?

Answer 13

→ some have symptoms, some never will

Symptoms: variable

• ALT elevation: 1.5-10-fold
• Prognosis: variable, at risk for progression
• Treatment: at underlying cause

Question 14

What are the different diseases that are cases of acute hepatitis and what are the clues/tests?

Answer 14

Hepatitis A: exposure history (clinical clues), IgM anti-HAV (diagnosis test)

Hepatitis B: risk factors (clinical clues), HBsAg, IgM anti-HBc (diagnosis test)

Drug-induced: compatible agent and timing (clinical clues), improvement after d/c agent (diagnosis tests). I.e. Tylenol at low doses is safest thing, but if overdose, can kill liver right away.

Alcoholic hepatitis: History of alcohol excess, ALT > 2, AST < 400 (clinical clues), biopsy (bx), improvement with abstinence (diagnosis tests). AST is higher than ALT (due to a vitamin B deficiency bc of malnourishment)

Ischemic hepatitis: history of hypotension (clinical clues), rapid improvement of ALT (diagnosis tests). → Lack of blood flow to the liver

Question 15

What are the different diseases that are cases of chronic hepatitis and what are the clues/tests?

Answer 15

Hepatitis C: risk factors (clinical clues), anti-HCV, HCV RNA (diagnosis tests)

Hepatitis B: risk factors (clinical clues), HBsAg (diagnosis tests)

NASH or NAFL: obesity, DM, hyperlipidemia (clinical clues), US, liver biopsy (diagnosis test)

Hemochromatosis: arthritis, DM, family history (clinical clues), iron studies, gene test (diagnosis test)

Alcoholic liver disease: History of alcohol excess (clinical clues), biopsy, improvement with abstinence (diagnosis tests)

Autoimmune hepatitis: ALT 200-500, female, other autoimmune disease (clinical clues), ANA, ASMA (diagnosis tests)

Question 16

Why is itchiness related to cholestatic?

Answer 16

Because bile acids will deposit in skin and make it itchy.

Question 17

What is palmar erythema?

Answer 17

Red hands due to hyperestrogenemia

Question 18

What is spider angiomata?

Answer 18

Spider-like texture on skin due to excess estrogen again

Question 19

What are abnormal liver tests for cholestasis?

Answer 19

• Patients have modest elevation of alkaline phosphatase
• Symptoms often include fatigue and pruritus (severe itching of skin) at the end
• Prognosis: at risk for progression

Important to differentiate intrahepatic versus extrahepatic (usually obstructive) causes
→ if small duct problem, can’t be fixed or surgically repaired

Question 20

True or false: NASH can only lead to hepatitis.

Answer 20

False. NASH can cause both cholestasis and hepatitis

Question 21

What is the protocol to detect liver damage?

Answer 21

First measure the ALP levels → if they are elevated, could mean liver problem, high bone turnover or presence of a placenta, so measure GGT levels
→ if abnormal levels, then proceed with a liver ultrasound, if normal, pursue a nonhepatic cause
→ after the liver ultrasound, notice if the problem is either a dilated duct, a liver mass, or normal.
If it is a liver mass → ERCP (endoscopic retrograde cholangiopancreatography), if it is a liver mass → further imaging required, tumor markers as well as biopsy. If normal, pursue intrahepatic causes, antimitochondrial antibody, careful drug history and consider biopsy.

Question 22

How do you diagnose conjugated hyperbilirubinemia?

Answer 22

Bilirubin is < or equal to 15 mg/dL (250 umol/L) in pure obstruction

Bilirubin > 20 mg/dL (350 umol/L) implies a nonobstructive (or mixed) cause

Bilirubin will be > 80% unconjugated and less than 5 mg/dL in hemolysis (85 umol/L)

Pain, fever, and/or palpable gallbladder imply obstruction

US (ultrasonogram) or CT may not detect dilated ducts in an acute obstruction

Question 23

What is cirrhosis?

Answer 23

End stage of any chronic liver disease. It is characterized histologically by regenerative nodules surrounded by fibrous tissues (= lumpy liver). There are two clinical stages = compensated is when it is working fine, decompensated is when not working (can kill).

Question 24

What is the development of chronic liver disease?

Answer 24

Chronic liver disease –> Compensated cirrhosis (where complications develop: variceal hemorrhage (spewing out blood bc of GI damage), ascites (fluid leaks out of liver in belly), encephalopathy (slurring, build up of ammonia in brain), and jaundice) → decompensated cirrhosis → death
→ decompensated cirrhosis shortens survival

Question 25

What are the complications of cirrhosis?

Answer 25

Cirrhosis can firstly lead to portal hypertension, which causes variceal hemorrhage, ascites and encephalopathy. Ascites also lead to spontaneous bacterial peritonitis as well as hepatorenal syndrome. The second thing cirrhosis can induce is liver insufficiency, which is linked to encephalopathy as well as jaundice.
Portal hypertension can also lead to splanchnic and systemic vasodilation, lowering the effective arterial blood volume, which causes the activation of neurohumoral systems (RAAS), leading to sodium and water retention, expanding plasma volume, causing a hyperdanim circulation. This is cyclic and causes constant elevation of BP. The way to intervene is to fix the sodium intake of patients with hyperdynamic circulation.

Question 26

Why is nutrition in cirrhosis hard to assess?

Answer 26

Some patients with cirrhosis will also have sarcopenia, which is having a huge belly full of fluid, which doesn’t give a distorted image of the patient’s health in some cases. Being sarcopenic increases overall mortality and nutritional supplements at night will increase muscle mass (help counter muscle wasting).

Question 27

What effect does being obese have on NASH patients’ blood pressure?

Answer 27

Being obese with NASH increases both systolic and diastolic blood pressure. Diastolic dysfunction is how stiff your heart is, how hard it is for your heart to relax.

Question 28

What is NASH?

Answer 28

Non-alcoholic steatohepatitis is a disease that histologically mimics alcoholic hepatitis and that also may progress to cirrhosis. It is the #1 most common disease in the developed world. There is an increase in hepatocyte death in addition to steatosis. The liver injury triggers a repair response that sometimes leads to cirrhosis.

Question 29

Can fatty liver (steatosis) predict hepatitis or other liver damage?

Answer 29

No, because many people can have fatty liver and not get sick from it. Some other cases will progress to hepatitis more quickly than others.

Question 30

What is the clinical syndrome (definition) for NASH?

Answer 30

Obesity, diabetes, hypertension and hyperlipidemia (specifically triglycerides!!!). No alcohol consumption (20g vs 40g), and the absence of other causes of liver disease.

Question 31

Who is at risk of NASH?

Answer 31

Overweight/obesity, asian populations (need to consider BMI shift, so overweight more easily), underweight or anorexic patients (increased liver fat with low intake).

Question 32

What are ballooning hepatocytes?

Answer 32

When fat infiltrates hepatocytes, which makes them explode after a while.

Question 33

Why is low albumin alarming in liver disease and how can it be noticed?

Answer 33

Albumin is made in the liver, so if levels are low, there is most probably and issue with the liver. A symptom of hypoalbuminemia is Terry’s nails, which is when the white part at the bottom of nails goes much higher than normal nails.

Question 34

What is the prevalence of NASH?

Answer 34

It has an overall prevalence of 20%, with 3% in non-obese, 19% in obese and 50% in morbid obese.

Question 35

What are the major risk factors for advanced liver disease?

Answer 35

Older age (>45)
Obesity (BMI > 30)
Long-standing diabetes (> 15 yrs)
Triglycerides > 5.65 (2.8?) mmol/L → assured fatty liver > 5.65, > 2.8 could get it
AST > ALT
ALT > 2 x ULN and/or AST > normal

Question 36

What does a fibroscan measure?

Answer 36

It measures stiffness of the liver and the fat content without having to use an invasive technique such as liver biopsies.

Question 37

How can liver disease be treated?

Answer 37

Even though diet is the treatment most commonly proven to help in clinical trials, other options were shown to also have a positive effect in certain studies such as statin/fibrate against hyperlipidemia, antihypertensives, drugs for obesity and pentoxifylline.

Question 38

What are the weight loss/exercise recommendations for liver disease?

Answer 38

A 5-10% weight loss was shown to help in treating obesity through diet and exercise in order to help with liver disease. It was also shown that intensity of PA might be more important than duration, which significantly reduced or of having NASH. For weight loss, Orlistat was used to get to the target weight loss of 9-10% to notice improvement in histology.

Question 39

Which new therapy is tested to be able to treat NASH through storing glycogen instead of fat?

Answer 39

GLP-1 agonists are used to stimulate insulin secretion from the pancreas, which would stimulate glycogen storage over fat storage in the liver.
FXR agonists reduce portal hypertension and lowers lipids by working through a nuclear receptor to reduce cholesterol synthesis.

Question 40

Why may rapid weight loss be dangerous for the liver (bariatric surgery for example)?

Answer 40

Jejunoileal bypass in particular has been shown to cause a drastic weight loss in its patients, which causes the liver to overproduce fat, leading to increased steatosis, cirrhosis,liver failure and gallstones. If weight loss if gradual, works fine.

Question 41

What are the different therapies for NASH?

Answer 41

In diabetics = aggressive glucose control using TZDs

In non-diabetics = vitamin E 800 IU, safety?

In hypertension = aggressive Rx; consider ARB or ACE-I
In hyperlipidemia = aggressive Rx; consider fibrates or statins

Diet and exercise with intial target of 10% weight loss = modify diet composition.

Vigorous exercise is encouraged where safe

Modest alcohol consumption may be protective for NAFLD patients

When appropriate, consider surgical options such as bariatric or transplant