The results of the tests performed by the doctor are now available (Table 5.1). HCV antibodies indicate HCV infection (chronic hepatitis) and the patient will require HCV RNA, liver biopsy and possible treatment with anti-viral therapy with pegylated interferon and ribavirin, or with one of the newer protease inhibitors (boceprevir or telaprevir).

Table 5.1 Further investigations into the cause of the abnormal liver function test

Test	Result	Implication
Repeat LFTs	Similar to above
Hepatitis A	IgG positive IgM negative	Patient has been infected with HAV in the past or immunised. This virus does not cause chronic liver disease
HBsAg	Negative	See below
HCV antibodies	Positive
Autoantibody screen	Negative	Positive titres usually found in autoimmune hepatitis
Serum ferritin	110 µg/L	This excludes hereditary haemochromatosis

Armed with the HCV result you discuss IV drug use with your patient, who then admits to the very occasional use of IV drugs in the 1960s.

Although this patient did not have HBV, you need to know the significance of HBV markers (Table 5.2).

Table 5.2 Significance of viral markers in hepatitis B

From Kumar and Clark Clinical Medicine, 8th edn, 2012.

Progress.

This patient was referred to the Liver Clinic. Her HCV RNA showed 45 000 IU/ml viral load. She was treated with pegylated interferon and ribavirin and at 3 months she had a good response with a 2 log reduction in RNA. She stopped therapy at 6 months and continued to be followed up in the clinic.

Jaundice

Jaundice is detected clinically when the serum bilirubin is greater than 50 µmol/L (3 mg/dL).

Case history (1)

A 45-year-old woman has been admitted to MAU with deep jaundice. She gives a history of two episodes of severe abdominal pain which had lasted for about half an hour. She has lost her appetite and consequently lost some weight.

Abdominal examination is unhelpful; there were no signs of chronic liver disease.

The blood tests showed a raised serum bilirubin, an ALT of 50 units and a high alkaline phosphate of 410 units. You order an ultrasound examination of the liver and biliary tree as you suspect that she has got gallstone disease (Fig. 5.1).

Figure 5.1 Clinical presentation of gallstones.

Investigations

• Blood count, liver biochemistry

• Liver function (INR and albumin)

• Abdominal ultrasound

• Viral markers to exclude hepatitis causing intra-hepatic cholestasis

Ultrasound in extra-hepatic obstruction can show:

• Dilatation of the intra-hepatic biliary tree

• Dilatation of the common bile duct

• Gallstones in the gall bladder

• Gallstones in the biliary tree

• A pancreatic mass

• Metastatic liver disease.

In this patient, the ultrasound showed gallstones in the gall bladder and a dilated common bile duct. Provided this patient’s clotting is satisfactory, the next procedure should be an ERCP. This would enable a better visualisation of the system and would allow a gallstone that is causing the obstruction in the common bile duct to be removed. A sphincterotomy would need to be performed beforehand and the stone could be removed with a basket or a balloon. If the stone is very large, the stone can be crushed and the debris removed. In an elderly patient, stent insertion to maintain drainage is an option.

Progress.

In this patient the stones were cleared from the common bile duct at ERCP and this was followed by a laparascopic cholecystectomy.

Remember

• Cholangitis often accompanies gallstones obstructing the biliary tree and urgent duct drainage should be performed. Antibiotics (e.g. ciprofloxacin 500 mg × 2) should be given.

• The residual stones are removed endoscopically when the patient has recovered.

Case history (2)

A 78-year-old man is admitted with marked jaundice. He was previously fit and well but the ultrasound arranged by his doctor showed a dilated biliary system with the probability of a pancreatic mass.

An endoscopic ultrasound and/or CT scan should be performed to assess the vague possibility of operability.

An ERCP with placement of a stent through the stricture enables drainage and is the usual treatment. This makes the patient feel a lot better as well as relieving the jaundice. This was performed in this man.

Jaundice without pain is quite common with carcinoma of the pancreas but with gallstones there is usually a history of biliary pain accompanying the jaundice.

Complications of ERCP sphincterotomy (complication rate 8–12%)

• Bleeding (severe in 2%)

• Perforation

• Acute pancreatitis (5%)

• Cholangitis.

Case history (3)

A 20-year-old woman is admitted in a confused state and deeply jaundiced. She has recently returned from India, where she had been trekking; she had had a major argument with her boyfriend. A subconjunctival haemorrhage was noticed on examination.

This patient is critically ill with fulminant hepatic failure and it is essential to stabilise her as soon as possible.

A central venous line was inserted and as her haemoglobin was very low, she was given 2 units of red blood cells. The clotting studies give an indication of the degree of damage to her liver, and will be useful for daily follow-up. It is also necessary to make sure that the patient’s potassium and blood sugar are satisfactory and whether replacements are necessary.

Investigations

• Haemoglobin

• Clotting studies and albumin

• Liver enzymes

• Blood sugar

• U&E

This woman’s investigation showed a bilirubin of 130 µmol/L, ALT 900 U/L, AST 785 U/L, alkaline phosphatase 109 U/L, albumin 34 g/L, INR 2.2, indicating severe hepatocellular damage.

Further management

This patient is liable to infection and intravenous antibiotics are required after blood cultures have been taken.

Remember

Hepatic encephalopathy should be treated with a low-protein diet and lactulose.

It is essential to try to establish a cause of this patient’s jaundice. This might be hepatitis A or hepatitis E – both are endemic causes of hepatitis in India and often follow an initial respiratory type of illness; they can occasionally cause fulminant liver damage. A paracetamol overdose is also a possibility, as her boyfriend said that she was very upset when they returned to the UK.

Further investigation

Viral markers for the above causes, and paracetamol levels, must be obtained urgently. Other investigations would include the following if no cause has been found:

• Autoantibodies

• Copper studies

• Alpha-1 anti-trypsin levels.

In this case, the patient’s relatives arrive and say they have found empty containers labelled paracetamol 500 mg tablets in her bedroom at her apartment.

The patient might well stabilise at this stage but a close eye will need to be kept on her for potential infections, particularly with opportunistic organisms. It is reasonable to give Acetylcysteine in the initial management of such comatosed patients, whether or not the paracetamol blood level is high.

This patient’s clinical condition deteriorated, with a modified early warning score (MEWS) score of 5. She became increasingly drowsy and confused and developed a flapping tremor and fetor hepaticus. Her investigations now showed a serum bilirubin of 320 µmol/L, ALT 4200 U/L, AST 3800 U/L, serum albumin 32 g/L, with an INR of 3.62. Urgent advice was sought from the nearest liver unit.

Information

Criteria for transfer to a specialised unit:

• INR > 3.0

• Presence of hepatic encephalopathy

• Hypotension after resuscitation with fluid

• Metabolic acidosis

• Prothrombin time (seconds) > interval (hours) from overdose (in paracetamol cases)

You arrange for transfer. In specialised units 70% of patients with paracetamol overdose and grade IV encephalopathy survive. Factors that indicate a poor prognosis with paracetamol overdose (without transplantation) are:

• Arterial pH < 7.3 OR

• Serum creatinine > 300 µmol/L

• Prothrombin time > 100 s

• Grade III–IV encephalopathy.

Progress.

This woman was seriously ill with acute hepatic failure. She survived with supportive therapy without transplantation being necessary.

Acute liver disease

Case history

A medical student turns up in A&E with jaundice. He is very worried that he has gallstones and might need surgery. He has never seen jaundice outside a surgical ward.

How do you approach this situation?

First, you point out that gallstones are rare in a young person and that a viral hepatitis is, by far and away, the most likely diagnosis. You quickly ascertain that he has been previously immunised against hepatitis B and only drinks beer after rugby. He denies IV drug use. Your thoughts now turn to how he acquired hepatitis A. There is no clue from the history:

• No contacts with jaundice

• No prodromal features

• No travel abroad.

On examination, apart from jaundice, there are no other abnormal signs.

Take blood for:

• Liver biochemistry

• HAV IgM (to indicate acute HAV infection).

You tell him to go back to his student flat, be careful with his personal hygiene and return in 2 days for his results (Table 5.3).

Table 5.3 Test results in acute liver disease

Test	Result	Implication
Serum bilirubin	70 µmol/L
AST	300 iu/L	Compatible with acute
ALT	280 iu/L	hepatitis
ALP	140 iu/L
HAV IgM	Negative

Oops! HAV IgM negative! You realise that although hepatitis A is very, very common in such a situation there are other causes. You had omitted to take a careful drug history from someone you knew (NB: remember Ecstasy!).

Progress.

This student turned out to have glandular fever (EBV infection), which can occasionally present with jaundice.

Ascites

Ascites is fluid within the peritoneal cavity due to sodium and water retention, e.g. cirrhosis or heart failure or secondary to malignant deposits.

Case history (1)

A 45-year-old woman presents with ascites gradually increasing over 2 weeks.

Examination shows no abnormality outside the abdomen.

Determining the cause of the ascites is essential to developing a management plan and she is admitted to MAU.

Investigations

• Liver biochemistry

• FBC

• INR and serum albumin

• Ascitic tap – for white cell count, culture, protein, malignant cells

Information

Paracentesis (ascitic tap):

• Obtain the patient’s consent after explaining procedure

• Percuss the dull area in the RIF

• Clean the skin and inject local anaesthetic (1% lidocaine) into skin using orange needle

• Insert 21-gauge needle (green) on a 20 mL syringe into the fluid

• Withdraw approximately 20 mL

• Withdraw the needle and apply dressing

Ascitic fluid

The ascitic protein concentration, as well as the serum : ascites protein gradient (SAG) help differentiate a transudate (< 25 g/L or SAG > 11 g/L) from an exudate (> 25 g/L or SAG < 11 g/L).

In this case, a high ascitic protein (> 25 g/L) suggests tumour or infection.

Malignant cells were present; further imaging with ultrasound – abdominal and pelvic – CT were performed to determine tumour site.

Diagnosis.

In this patient, the age and sex suggested an ovarian malignancy and this was confirmed.

Progress.

She was referred to the Gynaecology Department for further management.

Case history (2)

A 45-year-old man has attended his doctor on many occasions with alcohol-related problems. He is sent up to A&E with a swollen abdomen. He admits to drinking 60–80 units per week for 20 years.

On examination he is not jaundiced, but he has spider naevi, liver palms, Dupuytren’s contractures and testicular atrophy. He has gross ascites and pitting ankle oedema.

Immediate management

• Bed rest

• Salt restriction

• Daily weights and U&Es.

• Start diuretics – spironolactone 100 mg/day (increasing gradually to 400 mg/day) to obtain a weight loss of 500 g/day

• If inadequate response to above, introduce furosemide 40–120 mg/day

• Give thiamine 25–50 mg daily.

The patient must stop drinking.

Subsequent management

It may be necessary to do a liver biopsy to confirm the cause of cirrhosis, but only after the ascites is removed. If it is impossible to do a percutaneous liver biopsy (due to ascites, prolonged clotting), then biopsy can be undertaken through the jugular vein under X-ray control.

Progress.

This patient was referred to the Alcohol Dependency Unit after resolution of his ankle swelling and ascites. He may require liver transplantation and he should be referred on to a Liver Unit for assessment. He continues to abstain from alcohol but at present he does not fit the criteria for transplantation (MELD Score 7).

Resuscitation

• IV access

• CVP assessment

• Fluid replacement (initially with colloid)

• Blood transfusion

• O₂ for shocked patients.

Remember

Hb < 100 g/L, urea ↑, postural hypotension present, pulse rate 110/min. This patient is severely compromised and needs urgent treatment.

The gastroenterologists and surgical teams were informed. He was admitted to the high-dependency unit, a CVP line was inserted.

Many hospitals have multidisciplinary teams and protocols. Keep the patient nil by mouth until the bleeding has stopped. Causes of upper gastrointestinal bleeding are shown in Figure 5.2.

Figure 5.2 Causes of bleeding.

A further history of this man revealed that he had a high alcohol intake of 70 units/week for many years. He had no history of long-term dyspepsia and did not take NSAIDs, including aspirin.

On examination he had signs of chronic liver disease with spider naevi and gynaecomastia. His liver was 4 cm palpable and he had splenomegaly.

Remember

Shock:

• Pallor

• Cold nose

• ↓ Systolic BP.

The common causes of a GI bleed are

• Oesophageal varices

• Peptic ulcer

• Gastric cancer

• Gastric erosions.

Management

His haemoglobin returned as 90 g/L and the urea was raised at 10 mmol/L. A blood transfusion was started to resuscitate him (Fig. 5.3). On improvement he had an endoscopy which showed oesophageal varicies and these were banded (Fig. 5.4). On return to the ward he had a further haematemesis 4 hours later. Vasoconstrictor therapy was given.

Figure 5.3 Management of gastrointestinal haemorrhage due to oesophageal varices. TIPS, transjugular intrahepatic portosystemic shunt.

Figure 5.4 Oesophageal varicies (a), with band in place (b).

(Kumar and Clark Clinical Medicine 8th edn, 2012, p. 333).

Vasoconstrictor therapy

The main use of this is for emergency control of bleeding whilst waiting for endoscopy and in combination with endoscopic techniques. The aim of vasoconstrictor agents is to restrict portal inflow by splanchnic arterial constriction.

• Terlipressin. This is the only vasoconstrictor shown to reduce mortality. Dose is 2 mg 6-hourly, reducing to 1 mg 4-hourly after 48 hours if a prolonged dosage regimen is used. It should not be given to patients with ischaemic heart disease. The patient will complain of abdominal colic, will defecate and have facial pallor owing to the generalised vasoconstriction.

• Somatostatin. This drug has few side effects. An infusion of 250–500 µg/h appears to reduce bleeding, but has no effect on mortality. It should be used if there are contraindications to terlipressin.

Balloon tamponade with a Sengstaken–Blakemore tube can be used if the bleeding continues. Use the gastric balloon only initially but, if the bleeding is not controlled, inflate the oesophageal balloon, remembering that continuous inflation leads to oesophageal damage. It has serious complications and should be left in situ for only 24 h.

If these measures fail, transjugular intra-hepatic portosystemic shunt (TIPS) might be required and is often used as the treatment of choice for gastric varices.