Liver, biliary, pancreas

Question 1

Please could you tell me the normal range of values for the liver function
test serum alkaline phosphatase. The only mention of the parameters is
that a reading of 1000 serious liver condition.

Answer 1

The normal serum alkaline phosphatase is 40–100 IU/L. Levels of 400
are common in cholestatic liver disease. Levels of 1000 and over are
seen in primary biliary cirrhosis and liver metastases. (Note: remember
alkaline phosphatase is also found in bone so that bone disease,
e.g. Paget’s, is also associated with a raised serum alkaline phosphatase.)

Question 2

What is the best single test of liver function to exclude liver cell failure in
the routine work-up of a patient with early dementia?

Answer 2

Liver function is assessed with the serum albumin as the well as the
prothrombin time. The other routine liver tests, e.g. transferases and
alkaline phosphatase reflect liver damage not function. You can therefore
measure either the prothrombin time or the albumin.

Question 3

How valuable is the measurement of the liver span in a physical
examination?

Answer 3

Quite useful but less valuable since the widespread use of ultrasound
scans.

Question 4

Why has the term ‘chronic liver disease’ replaced terms such as ‘chronic
hepatitis’? What exactly does this new term mean and what conditions
does it cover?

Answer 4

Chronic liver disease is a general term for all types of liver disease that
are chronic (by definition greater than 6 months’ duration). It has not
replaced terms such as chronic hepatitis, which is used for a hepatitis that
is chronic.

Question 5

Can jaundice occur early in schistosomal hepatic fibrosis and, if so, how?

Answer 5

No. Hepatocellular function remains good.

Question 6

My patient has been found to have a serum bilirubin of 34 μmol/L
(2mg/dL) on three occasions. The other liver tests are normal. He tells
me he has Gilbert’s disease; how can I prove this?

Answer 6

In Gilbert’s, hepatic glucuronidation of bilirubin is 30% of normal so that
there is excess of unconjugated bilirubin. To prove the diagnosis you
should measure the total and unconjugated bilirubin in the serum, the
unconjugated will be high. A normal reticulocyte count will exclude
haemolysis and you have the diagnosis. Genetic studies are not
necessary.

Question 7

Why is urinary urobilinogen increased in haemolytic jaundice? If the
bilirubin in this condition is unconjugated, how does it reach the terminal
ileum to be converted into urobilinogen?

Answer 7

This is because increased unconjugated bilirubin also leads to some
increase in conjugated bilirubin, which can then be secreted into the gut
and converted to urobilinogen.

Question 8

How does cholestatic jaundice affect the kidney?

Answer 8

Cholestatic jaundice does produce tubular necrosis, albeit rarely. This can
occur following surgery. It can be prevented by intravenous infusion of
mannitol.

Question 9

What is the mechanism by which cholestatic jaundice causes

bradycardia?

Answer 9

It used to be said that this was due to the effect of the high level of bile
salts on the sinoatrial node. However, recent evidence suggests that
bradycardia in adults is rare in cholestatic jaundice.

Question 10

Are ‘jaundice’ and ‘icterus’ one and the same? I was taught that icterus
is yellowing of the sclera, while jaundice is yellowing of the skin and the
mucous membranes. As a result, carotenaemia can produce jaundice but
not icterus: is this so?

Answer 10

‘Jaundice’ and ‘icterus’ are the same. In the main, people use the word
‘jaundice’ most of the time. ‘Anicteric’ is sometimes used to describe
a person who is not jaundiced

Question 11

biological effect of hepatitis: how exactly does it

affect the liver?

Answer 11

Hepatitis means inflammation of the liver. It can occur from many
causes but in your patient the hepatitis C virus seems to have been the
cause of the inflammation. 60–80% of patients who develop hepatitis
C go on to chronic liver disease; 20–30% of these will develop cirrhosis
of the liver over a period of 20–30 years. The damage to the liver in
the chronic situation is due to the immunological response to the
hepatitis C virus.

Question 12

admission criteria for a case of acute viral hepatitis?

Answer 12

Most patients with acute viral hepatitis do not need to be admitted to
hospital. Patients who appear to be developing hepatic failure do need
admission. Clinical features are then of a severely jaundiced patient with
some degree of drowsiness.

Question 13

hepatitis B virus (HBV)
infection: chronic carrier, asymptomatic [normal liver function tests, HBV
DNA/real-time polymerase chain reaction (PCR) 240 copies/mL, core
less than 0.1]. Does a patient with such a profile need therapy or fine
needle aspiration (FNA) biopsy? What is the possibility of hepatocellular
carcinoma (HCC) in such a patient?

Answer 13

The patient described is sometimes referred to as a ‘healthy carrier’.
These patients seem tolerant of the virus and the prognosis is very good.
Liver histology in such patients shows no significant damage and
biopsies or therapy are not recommended.
90% of patients who are HBV carriers who develop HCC have
cirrhosis, which is rare in a healthy carrier as described above

Question 14

In chronic hepatitis B virus (HBV) infection, when anti-hepatitis B e
antibody (anti-HBe) develops (seroconversion), the antigen disappears
and there is a rise in alanine transferase (ALT). However, the graph in
your book (K&C 7e, p. 337, Fig. 7.16) seems to show a fall in ALT at this
point. Which is correct?

Answer 14

When seroconversion occurs there may be a ‘flare’, i.e. a short rise in ALT,
but then the ALT falls usually to normal. This is reflected in the graph.

Question 15

Interferon can be used in prophylaxis from hepatitis C after exposure.
Could you explain how this can be used, and what degree of success can
be expected as a result?

Answer 15

Monotherapy with 5 M units daily for 4 weeks then 5 M units three times
a week for 20 weeks of alpha-interferon was used in one trial with a high success rate, (i.e. no RNA detected). Pegylated interferon is now used
instead because of its better side effect profile.

Question 16

What is the latest recommended drug treatment for hepatitis C?

Answer 16

Pegylated interferon combined with ribavirin. The dosage and length of
treatment depends on the genotype.

Question 17

Can hepatitis C disease be treated in a carrier state completely by giving
interferon?

Answer 17

There is strictly no carrier state for hepatitis C because there is always
some degree of liver damage in patients who have persistence of
the virus.
At the present time, the treatment of hepatitis C is pegylated interferon
and ribavirin. Treatment should be given to those patients with chronic
hepatitis on liver histology, HCV RNA in their serum and who have had
raised serum aminotransferases for more than 6 months. Patients who
have persistently normal aminotransferases and abnormal histology can
also be treated with the same combination.

Question 18

I am a carrier of hepatitis C (HCV) and am going to have antiviral
treatment soon. Are the side-effects of antiviral treatment for HCV bound
to occur? I am very worried.

Answer 18

Some side-effects are almost universal with interferon, although
pegylated interferon produces fewer side-effects. You must discuss the
treatment with your specialist.

Question 19

Besides needle-pricks, how else is it possible to contract hepatitis C from
a hepatitis C (HCV)-positive patient? Are the patient’s skin/sweat (or
other bodily secretions) infectious?

Answer 19

Only blood spread is implicated in HCV hepatitis. Sexual spread is rare.

Question 20

What is the risk of infection with hepatitis C from blood splashed into
the eyes?

Answer 20

It is rare. There is only one reported case.

Question 21

Hepatitis C (HCV): if results from the polymerase chain reaction (PCR)
examination are inconclusive, what does this mean? Should further
investigations be undertaken and, if so, will there be a risk of chronicity?

Answer 21

PCR testing for HCV RNA is very variable, depending on the laboratory
used and on the technique. In addition, the HCV RNA may only be
present in small amounts and viraemia may be intermittent. Repeat tests
at 6 months.

Question 22

In a patient with hepatitis C and autoimmune hepatitis, can

corticosteroids be prescribed for the autoimmune hepatitis?

Answer 22

Yes, under careful supervision. Treatment of the hepatitis C should also
be undertaken if treatment criteria are met.

Question 23

We were told that the more vascular a structure is, the more antigen
(HLA/blood groups) matching is needed for transplantation, e.g. cornea
transplant needs no matching. However, the liver is a very vascular
organ; I don’t know why liver transplantation needs blood group
matching only but renal transplantation needs much more HLA
matching.

Answer 23

The liver is a vascular organ that often behaves as a ‘privileged tissue’
in that little immune reaction occurs. The liver appears to induce a state of suppression by the secretion of large amounts of donor-soluble major
histocompatibility (MHC) class 1 antigen with the migration of large
numbers of donor dendritic cells from the donor liver into the host. This
was first shown by Sir Roy Calne in pigs.

Question 24

About steatohepatitis: please give me more information about the
occurrence of cirrhosis in such patients (non-alcoholic) and is there
any role and indication for lipotropic agents and hypocholesterolaemic
drugs?

Answer 24

Non-alcoholic steatohepatitis (NASH) is now thought to be a subgroup of
patients with non-alcoholic fatty liver disease (NAFLD). With NASH, not
only is there fat in the liver but there is inflammation on liver histology
obtained at biopsy.
Cirrhosis does occur in patients with NASH, so that liver biopsies are
probably indicated in patients with NAFLD and raised transferases (over
100 IU).
Weight reduction, drugs to lower cholesterol and triglycerides are
used but there is no good evidence of their efficacy.

Question 25

I am working on non-alcoholic fatty liver disease (NAFLD) but I did not
find anything regarding it. Can you tell me about its relationship with
lipids?

Answer 25

It has been recognized for many years that a fatty liver is sometimes
found in patients who do not drink alcohol. The term ‘non-alcoholic
steatohepatitis’ (NASH) was introduced in the 1990s. Subsequently, it has
been recognized that some patients have a fatty liver on biopsy with no
accompanying inflammation; this group is called non-alcoholic fatty liver
disease (NAFLD). It seems that only patients with evidence of NASH
on biopsy progress to chronic liver disease with fibrosis and cirrhosis.
Some of these patients do have high lipid levels (both cholesterol and
triglycerides) but this is by no means invariable. NAFLD is associated
with the metabolic syndrome

Question 26

Is NASH a valid term or not and what manifestation has it?

Answer 26

NASH, non-alcoholic steatohepatitis, was introduced a few years ago for
patients with fatty liver not due to alcohol. The meaning has now been
changed slightly in that the term ‘NASH’ is used only for a small group
of patients with non-alcoholic fatty liver disease (NAFLD) who have
inflammation as well as fat on liver histology.

Question 27

Is terlipressin better in controlling variceal bleeding than somatostatin?

Answer 27

Terlipressin has been shown to reduce mortality but has more side-effects
than somatostatin.

Question 28

Why is there a hyperdynamic circulation in cirrhosis?

Answer 28

The hyperdynamic circulation that occurs is partly due to the opening
of portosystemic collaterals. In addition, there are increased levels
of circulatory vasodilators, e.g. glucagon and vasoactive intestinal
polypeptide (VIP). There is also an increased production of nitric oxide,
which is a potent vasodilator.

Question 29

Why is there an increased level of immunoglobulin G (IgG) in patients
with cirrhosis?

Answer 29

Antigen absorbed from the gut bypasses the liver in cirrhosis and also
there is decreased function of the Kupffer cells in cirrhosis. Both of these
allow antigen to stimulate the reticuloendothelial system in the spleen
and lymph nodes to produce immunoglobulins

Question 30

Cirrhosis of liver is reversible according to your book. What is the
progress and when will we be able to counteract the ‘tissue inhibitors
of metalloproteinases’ (TIMPs) and thus save the lives of our
patients?

Answer 30

There is some evidence that fibrosis following liver damage is reversible.
There are no drugs currently available to act on TIMPS.

Question 31

What are the criteria for knowing the prognosis of cirrhosis (Child’s
criteria)?

Answer 31

Nowadays the model for end-stage liver disease (MELD) is used as
a predictor for liver transplantation in decompensated as well as
compensated liver disease. It is based on serum creatinine, serum total
protein and the international normalized ratio.

Serum bilirubin (mg/dL) 
Serum albumin (g/L) 
Ascites 
Encephalopathy 
1-year survival

Question 32

What is the recommended treatment for cirrhosis of the liver?

Answer 32

1. Treat the cause, e.g. stop alcohol, remove iron in hereditary
haemochromatosis.
2. Treat the complications:
● portal hypertension and bleeding
● ascites
● portosystemic encephalopathy.
3. Refer for liver transplantation

Question 33

Is there any role for liver dialysis in hepatic encephalopathy?

Answer 33

There is no role for liver dialysis in hepatic encephalopathy. We do not
know the toxic products that cause encephalopathy but they are too
small to be removed by dialysis.

Question 34

how long will it
take the liver to ‘recover’ or to return to normal after stopping drinking?
I am especially interested in blood tests, fatty deposits and gammaglutamyl
transpeptidases (γ-GTs).

Answer 34

It is difficult to answer these questions because it depends on how
abnormal the tests are when the patient stops drinking. Small elevations
in liver enzymes, e.g. alanine transferase (ALT) 80 units, will take weeks,
whereas an ALT of 200 units will take months. Indeed, the liver might be
permanently damaged. The γ-GT rises in response to alcohol ingestion as
well as liver disease. Moderate fat in the liver disappears within 3–4 months.

Question 35

Can patients with liver cell failure suffer from myocardial infarction?

Answer 35

Yes. Many patients with alcoholic liver disease also smoke, which is a
risk factor for coronary artery disease.

Question 36

What is the definition of liver cell failure (decompensated liver
disease)?

Answer 36

Decompensated liver disease is the term used to describe a patient
with chronic liver disease (cirrhosis) who develops complications, e.g.
bleeding, ascites or encephalopathy. In such a patient, the serum albumin
is usually low and the patient might be jaundiced. The term ‘liver cell
failure’ is sometimes used to describe acute hepatocellular failure or
fulminant hepatic failure.

Question 37

Flapping tremors: why do we get flapping tremors and no other types of
tremor in liver failure? What is their mechanism and in which other
conditions do they occur?

Answer 37

Flapping tremors occur in hepatic encephalopathy and in chronic
obstructive pulmonary disease with carbon dioxide retention. The
mechanisms are unclear but ammonia seems to be involved in the tremor
seen in hepatic encephalopathy.

Question 38

In a patient with liver cell failure, can there be resting and action tremors
or parkinsonian features if it is confirmed that the patient does not have
Wilson’s disease?

Answer 38

Yes; patients with hepatic encephalopathy can have basal ganglia signs
without having Wilson’s disease

Question 39

Does the absence of any cirrhosis of the liver, together with normal liver
enzymes, in a 9-year-old boy complaining of chorea of a 5-year duration,
exclude Wilson’s disease?

Answer 39

In this age group, it is usual for the liver disease to present first. The liver
disease is variable, from mild hepatitis to acute fulminant hepatitis and
also cirrhosis. If there is any doubt, Wilson’s disease should be further
excluded by examination of the child and investigation of copper levels
in the blood (low) or in the liver (high).

Question 40

Can Wilson’s disease be excluded in a patient complaining of movement
disorder for over 2 years, when there is an absence of cirrhotic liver change?

Answer 40

No; the liver disease is variable. Wilson’s disease should be excluded by
appropriate investigations of copper metabolism.

Question 41

What drugs cause Budd–Chiari syndrome?

Answer 41

Oral contraceptives have been implicated as a cause of Budd–Chiari
syndrome but, in general, drugs are not a cause of the pathology of this
condition.

Question 42

patient with pyrexia of unknown origin (PUO). He was
not particularly unwell and not jaundiced. But 1 week later he was found
to have a liver abscess on ultrasound. How can one make the diagnosis
earlier?

Answer 42

A liver abscess can present as a very indolent condition and it can take
a long time to diagnose. The best clues are a slightly raised alkaline
phosphatase and a raised serum vitamin B12. You must have a high
degree of suspicion

Question 43

most recent management of HCC (hepatocellular carcinoma)?
What is radiofrequency ablation? What is its role in the management of
HCC and its prognosis?

Answer 43

Hepatocellular carcinoma can be treated with surgical treatments:
● Resection
● Cryo-ablation
● Liver transplantation.
Non-surgical therapies are:
● Chemotherapy
● Radiation
● Chemoembolization
● Percutaneous ethanol injection
● Radiofrequency ablation.
Radiofrequency ablation involves passing a high-frequency alternating
current to the tip of an electrode that is placed in the cancer lesion. The ions in the tissue follow the change in direction of the alternating current,
producing frictional heat in the tissue to about 60°C. This produces a
thermal energy lesion. It is useful for small tumours and can be carried
out laparoscopically. In one series the patients’ disease was controlled
locally for 18 months

Question 44

How do you differentiate haemorrhagic ascitic fluid due to malignancy
and accidental rupture of blood vessel while withdrawing the fluid?

Answer 44

Accidental rupture of a blood vessel will sometimes produce a small
amount of blood, but usually there is no difficulty in differentiating from
haemorrhagic ascitic fluid.

Question 45

Is there any place for the medical treatment of gallstones with
ursodeoxycholic acid?

Answer 45

No, this treatment is now never used.

Question 46

In a case of common bile duct stones, where it is acknowledged that
spontaneous passage within 24 hours is observed in approximately 50%
of patients provided the stone is small, and that in these cases there is no
need for a sphincterotomy, is the use of antispasmodics, e.g. Buscopan
(active ingredient hyoscine-N-butylbromide), recommended? Surely these will reduce the pain and improve the chance of a spontaneous
release of obstruction without surgical procedure?

Answer 46

The problem with most antispasmodics is that they are not very effective
in vivo. OK, you could try Buscopan, but don’t be surprised if it doesn’t
work!

Question 47

What is sphincter of Oddi dysfunction?

Answer 47

This is a condition where there is increased tone in the sphincter
measured by manometry. It is usually diagnosed after cholecystectomy
when no stones can be found in the common bile duct to account for the
persistent right upper quadrant pain. True Oddi dysfunction is rare and
many patients have functional abdominal pain.

Question 48

I would like to know: what is the role of lysosomal hydrolases (cathepsin
B) in the pathogenesis of acute pancreatitis?

Answer 48

In early pancreatitis, cathepsin B cleaves the trypsinogen activation
peptide from trypsinogen within the acinar vacuoles, leading to activation
of trypsin. Trypsin is normally inactivated quickly but in this case defence
mechanisms are overwhelmed, leading to autodigestion of the pancreas.
Experimentally, inhibition of cathepsin B reduces pancreatic damage

Question 49

What is the role of octreotide in management of acute pancreatitis?

Answer 49

Octreotide has been used in the management of severe acute pancreatitis
because there is a significant mortality associated with the condition and
no very good treatment

Question 50

Why does paralytic ileus occur in pancreatitis?

Answer 50

In severe acute pancreatitis, pancreatic necrosis will release pancreatic
enzymes into the peritoneal cavity; this causes paralytic ileus.

Question 51

How sensitive is the increase in serum lipase levels in the case of acute
pancreatitis?

Answer 51

Between 85 and 100% sensitive. A radioimmunoassay is available, which
helps to overcome problems with the assay

Question 52

What is the association between chronic pancreatitis and peripheral
vascular disease (PVD)?

Answer 52

There is an association between smoking, chronic pancreatitis and PVD

Question 53

Please, can you explain to us the mechanism of pancreatitis in
hypertriglyceridaemias?

Answer 53

No! There is no good explanation. It has been suggested that release
of free fatty acids damages pancreatic acinar cells or capillary
endothelium.

Question 54

Is there any role for chemotherapy in carcinoma of the pancreas?

Answer 54

There is no consensus and further trials are being performed. If your
patients cannot be included in a trial, there is some evidence for
the use of 5-fluorouracil (5-FU) infusion after resection followed by
gemcitabine.

Question 55

1. How should portal hypertension be managed in patients with
   bronchial asthma, where beta-blockers are contraindicated?
2. How should diuretics for these patients with hypertension be added?

Answer 55

1. Beta-blockers are the best treatment but, if they cannot be used,
   endoscopic variceal banding is probably the best option.
2. Add in small doses slowly. Use spironolactone initially.

Question 56

Is cirrhosis a prerequisite for the development of hepatocellular
carcinoma (HCC) in hepatitis B (HBV)?

Answer 56

It is said that hepatocellular carcinoma can occur without cirrhosis but it
must be very rare.

Question 57

Should therapy with interferons in the treatment of hepatitis C (HCV)
and hepatitis B (HBV) commence when the polymerase chain reaction
(PCR) is positive, irrespective of serum glutamyl pyruvate transaminase
(SGPT) levels?

Answer 57

In chronic HBV infection, treatment is at present only given with
abnormal transferases. Some patients with HCV infection are being
treated with normal liver enzymes if liver histology is abnormal. Trials
are still ongoing.

Question 58

What is the degree of sensitivity of the CA19-9 as a marker of cancer in
the head of the pancreas?

Answer 58

It has sensitivity and specificity of 80–90% for established carcinoma. It is
too insensitive to be used as a screening test for pancreatic cancer

Question 59

What are the benefits and drawbacks of silymarin in the treatment of
liver cell failure?

Answer 59

Silymarin is extracted from milk thistle. It is a popular complementary
medicine which is said to ‘protect’ the liver. Its toxicity appears to be low
but there are no evidence-based reports to support its efficacy.

Question 60

If using zinc in the treatment of Wilson’s disease, should the salt used to
treat the disease be zinc acetate, or is any zinc-containing salt such as zinc
sulphate sufficient?

Answer 60

Oral zinc therapy blocks the intestinal absorption of copper. Both zinc
sulphate and acetate are used

Question 61

Is alkaline phosphatase of value in the differential diagnosis of jaundice?
If so, in what type is this raised?

Answer 61

The serum alkaline phosphatase is raised when the jaundice is
cholestatic. The level rises with both intrahepatic and extrahepatic
causes of jaundice so that you cannot be sure whether you are dealing
with hepatitis (intrahepatic) or common duct stones (extrahepatic). An
ultrasound scan is the definitive investigation and the ready availability
of the investigation makes the serum alkaline phosphatase in the
diagnosis of jaundice almost redundant.

Question 62

Metabolic syndrome (NCEP APT III*)
Three or more of the following:

Answer 62

● High blood pressure (130/85mmHg)
● Elevated serum triglycerides (150 mg/dL or 1.695 mmol/L)
● Decreased HDL cholesterol (40 mg/dL or 0.9 mmol/L in men and
50 mg/dL or 1 mmol/L in women
● Increased abdominal circumference [102 cm (40 inches) men or 88 cm
(35 inches) women]
● Impaired fasting glucose (110 mg/dL or 6.1 mmol/L)