case scenarios of gastroenterology

1. Dr Hafeez Yaqoob
Resident Gastroenterology BMCH

3. A 22-year-old male was admitted to hospital after
being found by his landlord with confusion. On
arrival at the hospital his Glasgow Coma Score was
13. He was apyrexial, with a blood glucose of
5.4mmol/L, pulse rate 60 beats/min and regular,
and blood pressure 114/58mmHg. Heart sounds
were normal and his chest was clear. He was noted
to be jaundiced. Asterixis was present. There were
no focal neurological signs. There were no spider
naevi, muscle wasting, or gynaecomastia. His only
medical history was pulmonary tuberculosis 6
months earlier, diagnosed by pleural biopsy and
pleural fluid analysis. He had last been followed up
2 months previously and was well at that time. He
had completed 2 months of rifampicin, isoniazid,
pyrazinamide and ethambutol, followed by
rifampicin and isoniazid alone.

4.  There was no record of any other medications
or over the counter preparations. There was
no known alcohol or drug history. HIV testing
had been negative. Investigations showed:
 ● Hb 15.2g/dL, WCC 9.1 x 109/L, platelets
173 x 109/L
 ● Na 135mmol/L, K 3.7mmol/L, urea
2.8mmol/L, creatinine 78µmol/L
 ● Bilirubin 357µmol/L, ALT 1307 IU/L, ALP
436 IU/L, albumin 32g/L
 ● Prothrombin time 53.8 sec.

5. 1a) What is the clinical syndrome illustrated by this
case?
1b) Give a differential diagnosis for the cause o(a).
1c) What blood tests would you request?
1d) What radiological tests would you request? 1e)
What is the management?
1f) What is the most likely cause in this patient and
why? What is the mechanism of injury?
1g) How might this problem have been prevented?

6. This is acute liver failure (ALF), which is defined
by three criteria:
● Rapid development of hepatocellular
dysfunction
(e.g. jaundice, coagulopathy)
● Encephalopathy
● Absence of a prior history of liver disease

7. Give a differential diagnosis for the cause of (a) The
differential diagnosis for ALF in this patient
includes:
● Drugs (paracetamol, antituberculosis
medications, PTU .
● Hepatotropic viruses (hepatitis B, hepatitis A,
hepatitis E, with hepatitis B being the most
common)
● Acute cryptogenic (non-A, non-B, non-C)
hepatitis

8.  ● Autoimmune hepatitis
 ● Ischaemia
 ● Metabolic disorders such as Wilson’s
disease
 ● Malignant infiltration.

9. A careful history of past and present medications
needs to be taken, together with a travel history and
assessment of risk factors to determine the
likelihood of acute viral hepatitis. Routine viral
testing should be done for all patients (see below).
In the presence of tense ascites Budd Chiari
syndrome (hepatic venous outflow obstruction)
should be considered, because ascites is unusual in
early acute liver failure from other causes. Wilson’s
disease may present with acute liver failure and
should always be considered in patients presenting
at a young age, but usually there is accompanying
haemolysis or renal failure, which were absent in the
present case. Furthermore, the alkaline phosphatase
is usually normal in Wilson’s disease, whereas in
this case it was elevated

10.  . Fulminant hepatic failure is an unusual presentation of
hepatic neoplasms, whether primary or metastatic.
Although this patient had ALF, it may be difficult to
distinguish this from acute decompensation of chronic
liver disease in patients in whom the past medical history
is unknown. For example, exacerbation of chronic viral
hepatitis (B and C) may produce a similar picture to ALF.
Patients with chronic liver disease, however, usually show
stigmata, including spider naevi, muscle wasting,
testicular strophy, or gynaecomastia, none of which were
present in this patient. Furthermore, in chronic liver
disease it would be rare for the prothrombin time to be
over 40 sec (usually it would be about 25 sec). In this
patient it was 53.8 sec. In alcoholic hepatitis, the alanine
transaminase (ALT) rarely exceeds 300 IU/L, (see box 2)
whereas in this case it was 1370 IU/L.

12. A ‘liver screen’ should be performed to look for the cause
of ALF including:
● Paracetamol concentration (although N-acetyl cysteine
should be started before the result is known, to cover the
possibility of toxicity). Note that paracetamol may be
undetectable if the overdose was over 72 hours before
blood testing
● Hepatitis A IgM
● Hepatitis B core IgM
● Autoimmune markers: antinuclear antigen (ANA), anti-
smooth muscle antibody (ASmAb), liver kidney microsomal
antibody type 1 (LKM1), and immunoglobulins
● Copper and caeruloplasmin to screen for Wilson’s
disease.

13. An ultrasound of the abdomen should be
performed, since this will help distinguish between
acute and chronic liver disease (splenomegaly is
more common in chronic liver disease). This is
particularly helpful in the context of a less severe
coagulopathy, where it may be unclear whether this
represents ALF or an acute exacerbation of chronic
disease. Ultrasound will not help to differentiate
between different causes of ALF.

14. The management of ALF includes:
● Intravenous rehydration: most patients require
liberal volume expansion, since such patients are
often vasodilated, volume depleted and acidotic.
The choice of fluid is not crucial and is usually a
mixture of crystalloid and colloid. Fluid
resuscitation can often reverse the acidosis.

15.  The blood glucose should be measured
hourly and replaced: with intravenous glucose
(10–50%) as necessary, since there is a high
risk of hypoglycaemia. Glucose
concentrations need to be maintained to
prevent the cerebral and systemic effects of
hypoglycaemia.

16. Arterial blood gas to monitor acidosis:
correction of lactic acidosis is important,
because it can affect circulatory function and
aggravate cerebral hyperaemia.
● N-acetyl cysteine should be given to cover
the possibility of paracetamol overdose.

17.  ● Antibiotics:
 prophylaxis with an intravenous cephalosporin is
recommended. Patients with ALF have a high risk
of infection and sepsis from bacterial and/or
fungal infection. The use of prophylactic antibiotics
is associated with lower rates of infection
complicating ALF. Without prophylaxis, infection
develops in up to 80% of patients with ALF, and
bacteraemia occurs in 20–25% (usually gram-
negative organisms). If definite infection is proven,
this should be treated aggressively (e.g.
vancomycin and a third-generation cephalosporin).

18. ● Vitamin K is not indicated: bleeding is unusual in
ALF despite the increased prothrombin time. Fresh
frozen plasma is not advocated, because the risks
(fluid overload, normalization of the prothrombin
time artificially) outweigh the benefits. Plasma
product should be used only if the patient is
bleeding or an invasive procedure is being
performed. The prothrombin time is also a good
prognostic indicator.
● Lactulose is of no proven benefit in ALF.

19. if the patient is not protecting their airway
(grade 3 or 4 encephalopathy), intubation and
ventilation is indicated. This applies
especially during transfer to a transplant unit,
because grade 4 encephalopathy can develop
rapidly.

20. In patients with acute liver failure, liver
transplantation should be considered at an
early stage and the regional liver transplant
unit contacted for advice. In paracetamol-
induced ALF, referral to a transplant unit
should be made if the prothrombin time is
>60 sec. For non-paracetamol acute liver
failure, the criteria are listed below

21. INR >6.5 or prothrombin time >100 sec OR
three of the following:
● patient age 40 years old
● serum bilirubin >300µmol/L
● time from onset of jaundice to development
of coma >7 days
● INR >3.5 or prothrombin time >50 sec

22. non-A, non-B, or drug toxicity (not paracetamol).
It should be noted that patients should be
transferred well before the development of these
criteria. The patient in this case met the criteria on
admission, since he had a prothrombin time of
53.8 sec, bilirubin of 357µmol/L, and drug toxicity
as the aetiology

23. The most likely cause of ALF in this patient is
isoniazid toxicity. One to two percent of patients
receiving isoniazid develop severe liver injury,
defined as an ALT being at least 3 times the upper
limit of normal. Fulminant hepatotoxicity is well
described and has 10–20% mortality if the isoniazid
is continued.

24.  The mechanism of injury is the production of toxic
metabolites through isoniazid oxidation in the
cytochrome p450 pathway. These metabolites
accumulate in people who are slow acetylators and
in those on concurrent enzyme-inducing
medication such as rifampicin or alcohol. Although
it remains controversial, certain polymorphisms of
N-acetyltransferase 2 (NAT2) and glutathione-S-
transferase genes are also thought to be risk
factors.

25.  Other risk factors for hepatotoxicity include
underlying liver disease (especially coexistent
hepatitis B or hepatitis C), other hepatotoxic
medications (such as protease inhibitors for
treatment of HIV), excessive alcohol
consumption, age >35 years, and female
gender. It is unclear whether race or
malnutrition contributes to the risk of
toxicity.

26. Before starting antituberculous treatment the
patient requires education regarding the
medication. Detection of risk factors for toxicity
(1f, above) is important and every patient should
have baseline LFTs. Individual patients need to be
aware that they should see a doctor if non-specific
symptoms occur

28.  Once the LFTs have normalized, antituberculous
drugs should be reintroduced one by one.
Rifampicin is usually introduced first and then
isoniazid.
 Pyrazinamide should be omitted if possible. These
drugs are often tolerated on reintroduction.

29.  If the ALT is >5 times normal, or if symptoms
arise, then antituberculous medications need to be
stopped. If the ALT is 2–4 times normal, then liver
function tests should be checked weekly for 2
weeks and then for monthly until they have
improved. If treatment needs to be continued,
alternative agents such as ethambutol or
fluoroquinolones should be considered, since these
are the least hepatotoxic.

30. A 52-year-old retired army major presented with
recurrent haematemesis and melaena. The patient
had been previously diagnosed with liver cirrhosis,
secondary to alcohol abuse. He had had two
episodes of variceal haemorrhage 2 years
previously, which had been controlled by
oesophageal variceal banding. He continued to
drink up to six standard alcoholic drinks per day.
He had type 2 diabetes, for which he was taking
metformin 500mg twice daily. He was also taking
spironolactone 50mg/day.
.

31.  On examination, he was very unwell with a pulse
rate of 110bpm, blood pressure 95/55mmHg,
oxygen saturation 95%, and temperature 35.8ºC.
There were multiple spider naevi, but no jaundice
or ascites. The patient was not confused and
there was no asterixis

32.  Hb 11.4g/dL, WCC 7.1 x 109/L, platelets 83 x
109/L
 ● Prothrombin time: 15.3 sec
 ● Na 134mmol/L, K 4.8mmol/L, urea 11.0mmol/L,
creatinine 104μmol/L
 ● Glucose 24.2mmol/L
 ● Bilirubin 35μmol/L, ALT 75 IU/L, ALP 100 IU/L,
GGT 320 IU/L,
 albumin 32g/L
 ● Gastroscopy showed four oesophageal varices
protruding half way
 across the lumen. Seven variceal bands were
applied with a good result.

33.  5a) How would you manage this patient prior to
endoscopy and what initial therapy would you
introduce following endoscopy?
 5b) What are the predictors of failure to control
variceal bleeding?
Unfortunately, the patient did re-bleed and
required another endoscopy, but the endoscopist
was unable to control the bleeding. By this stage
the patient had had 10 units of red packed cells
and remained tachycardic and
hypotensive.

34. 5c) What management should be considered at
this stage?
5d) Why did the patient became confused and
disorientated several days later?
5e) What is the subsequent management plan
for patients in whom acute variceal bleeding
is controlled endoscopically?

37.  Correct hypovolaemia
● Prophylactic antibiotics
● Vasoactive drugs
● Endoscopic therapy
● Treat and prevent encephalopathy.

38.  conservative:
blood volume resuscitation is currently
recommended,
 using packed red blood cells to maintain the
haemoglobin at approximately 7–9g/dL, and
intravenous colloid to maintain haemodynamic
stability.
 Crystalloid:
including saline, can be given in an emergency but
continuous saline infusion should be avoided,
because this will precipitate ascites and peripheral
oedema.

39.  helps avoid hypovolaemia, which is a
common cause of renal failure in such
patients

40.  volume overload increases portal pressure.
which can precipitate further bleeding

41.  often have a coagulopathy

42.  there is no evidence that fresh frozen plasma
or platelet administration is helpful, and there
is some evidence that it is harmful due to
volume expansion.

43.  The use of prophylactic antibiotics (oral quinolone
or intravenous ceftriaxone) should be standard
therapy for patients with cirrhosis who have
variceal bleeding. and should be instituted from
admission and continued for approximately 5 days.
An association with bacterial infection and variceal
bleeding has been shown in randomized trials.
Antibiotics decrease the rate of bacterial infections
including spontaneous bacterial peritonitis,
decrease the incidence of early re-bleeding, and
significantly improve survival.

44.  In suspected variceal bleeding, vasoactive
drugs (such as terlipressin) should be started
as soon as possible, before diagnostic
endoscopy.

45.  Vasopressin and its analogues, such as
terlipressin, cause splanchnic
vasoconstriction, leading to a reduction in
portal pressure.

46.  Randomized controlled trials have shown that
early administration of vasoactive drugs
reduces the rate of active bleeding, facilitates
diagnostic and therapeutic endoscopy,
improves the control of bleeding and may
decrease bleedingrelated mortality.

47.  Vasoactive drug therapy should be administered
for about 5 days, because this is the period in
which early re-bleeding is most frequent.

48.  The choice depends on local availability,
bearing in mind that the only drug shown to
improve survival is terlipressin.

49.  Somatostatin and octreotide:
have a similar effect on bleeding, but have
not been shown to improve survival.
Randomized controlled trials have shown that
the efficacy of vasoactive therapy is
significantly improved when combined with
endoscopic therapy.

50.  If vasoactive drugs are started as soon as possible
before endoscopy, the incidence of active variceal
bleeding during the endoscopy
decreases from 50% (when drugs are not used), to
20–25%

51.  Terlipressin and octreotride have fewer systemic
side effects, such as angina or gut ischaemia, than
vasopressin, but should still be used with caution
in people with a history of coronary artery disease.

52.  Endoscopy should be performed as soon as
possible after resuscitation, especially in patients
with active bleeding and features suggesting
cirrhosis.
 The aim is to stop bleeding by banding (ligation)
or sclerotherapy, and subsequently to obliterate
the oesophageal varices. Variceal wall tension is
the key factor that determines variceal rupture.
Endoscopic therapy reduces variceal wall tension
by reducing variceal size until obliteration, and
by increasing the thickness of the vascular wall.

54.  Variceal banding has proved more effective
and safer than sclerotherapy (with
ethanolamine) and is currently the
endoscopic treatment of choice for
oesophageal varices. Nevertheless, the choice
is also influenced by the availability of
equipment and expertise. Variceal obturation
with tissue adhesives such as cyanoacrylate
or with thrombin are generally limited to the
treatment of gastric varices.

55.  emergency endoscopic variceal banding and
antibiotic prophylaxis), has reduced 5-day
re-bleeding rates from 30% to 10–15%.

56.  Clinical factors associated with failure to control bleeding
and mortality
 are:
 ● Active bleeding at endoscopy
 ● Shock at admission
 ● Early re-bleeding (<5 days)
 ● Severity of liver disease (Child–Pugh grade: mortality in
patients with
 Class C = 70–80%)
 ● Raised bilirubin
 ● Prothrombin time (reflecting severity of liver disease)
 ● Thrombocytopenia (indirect measure of portal
hypertension)
 ● Encephalopathy

57.  Recent use of corticosteroids for alcoholic
hepatitis within 7 days of bleeding
 ● Age >60 years
 ● Complicating hepatocellular carcinoma.

58.  This patient has uncontrolled variceal bleeding
despite medical and endoscopic therapy. Such
patients are best managed with a transjugular
intrahepatic portal systemic shunt (TIPSS) . TIPSS is
an interventional treatment to decompress the
portal system by creation of an intrahepatic shunt
between the portal and hepatic veins. TIPSS is only
indicated for ‘salvage therapy’ when first-line
methods (medical and endoscopic) have failed.
Studies report immediate control of bleeding in
91–100% of cases, 30-day re-bleeding in 7–30%
and a 1-month mortality of 28–55%, reflecting the
severity of the underlying liver disease .

59.  Liver transplantation is not indicated
for an acute bleeding episode, but all such
people should be considered as transplant
candidates, if only to exclude this as an
option if (for instance) the person continues
to drink or has substantial comorbidity.

61.  The most likely explanation for the confusion in
this patient is post-TIPSS hepatic encephalopathy.
Hepatic encephalopathy is the main complication
that has limited the application of TIPSS. Clinically
evident hepatic encephalopathy develops in
approximately 35% of patients after TIPSS, most
often within the first 7 days

63.  The current regimen to prevent re-bleeding
in those patients who have controlled acute
oesophageal variceal bleeding is:
● Endoscopic eradication of varices (repeat
banding every 1–2 weeks until varices
eradicated)
● Combined with oral, non-selective beta-
blockers

64.  The combination is more effective than beta-
blockers alone in preventing late re-bleeding.