and Ian A. D. Bouchier2
(1)
Bishop Auckland, UK
(2)
Edinburgh, Midlothian, UK
The histology of the liver is an indispensable aid to diagnosis. It is the only way of proving the presence of cirrhosis, and it may also establish the cause of this disease, as in haemochromatosis and hepatolenticular degeneration. It has proved invaluable in the assessment of chronic hepatitis and alcoholic liver disease. The advent of other tests like elastography, and M2 antibody in PBC may reduce some of the requirement for histology. Normal elastography will exclude cirrhosis and significant steatosis, but abnormal results do not conclusively establish the cause.
13.1 Percutaneous Liver Biopsy
Since the liver is the largest organ in the body and is relatively constant in position, blind percutaneous biopsy is satisfactory in many patients. However, the use of ultrasound or CT guidance improves results in focal lesions and may be safer in parenchymal disease.
13.1.1 Preparation
The nature of the investigation is explained to the patient: it is important to obtain written consent. Blood is taken for measurement of haemoglobin, prothrombin time and platelet count. If there is any reason to suspect that these variables may change then the tests should be repeated on the day of the biopsy. A biopsy should not normally be performed unless the haemoglobin level is >100 g/l, the platelet count > 100,000/mm3 and prothrombin time no more than 3 s longer than control values. If patients are on anti-platelet or (unusually) anticoagulant therapy this will need to be reviewed and discontinued over the procedure. Liver biopsy should also be avoided in the presence of substantial ascites or when extrahepatic cholestasis seems likely. In anxious patients premedication with oral diazepam or IV midazolam may be helpful, but routine premedication is not necessary and may interfere with cooperation.
13.1.2 Procedure
The patient is positioned on the bed or trolley on which they will lie after the procedure. The patient lies supine close to the right edge of the bed. The right hand is placed behind the head which is supported by one pillow. The position of the liver is confirmed by percussion down the right side of the chest and abdomen. The puncture site is the point of maximal dullness between the anterior and midaxillary lines. This usually lies between the 8th and 10th intercostal spaces. The puncture site is positioned just above the appropriate rib, to avoid the vessels and nerves which run just below the ribs.
Occasionally, in case of difficulty or when a nodule can be palpated, a subcostal puncture may be made; this is a less satisfactory procedure even in the presence of marked liver enlargement.
It is not necessary to wear gowns or masks for this procedure, but the use of surgical gloves for the operator is recommended. A paper sheet placed under the patient prevents any leakage of blood onto the bedding.
The patient is instructed to practise the breath-holding procedure: after a full inspiration a full exhalation breath is held for a few seconds. During normal breathing the puncture site is thoroughly cleaned with alcohol swabs and infiltrated with 5 ml 2% lignocaine. The skin is anaesthetized with a fine needle, which is replaced by a 21 gauge needle to infiltrate down to the liver capsule with the breath held in expiration.
Two types of needle are in general use: both provide adequate biopsy samples.
The Menghini suction biopsy needle has been longer established and requires a shorter period of penetration of the liver. The Tru-Cut sheathed biopsy needle is slightly more cumbersome to use and much more expensive. An automatic needle (Biopty) did not confer any definite advantage.
13.1.2.1 Menghini Needle (Reusable) (Fig. 13.1)
The Menghini needle (Fig. 13.1) is supplied in a variety of calibres and lengths. For routine use the l.9 × 70 mm size is recommended. The slight theoretical advantage of smaller diameter needles is offset by the larger number of liver punctures required to obtain satisfactory tissue samples. The tip of the needle has a bevelled cutting edge. The needle is supplied with a blunt nail which fits inside the proximal shaft to prevent the sample being violently aspirated into the syringe, and with an external guard for the shaft to prevent too deep penetration of the liver: neither of these is essential. A trocar reminiscent of a sardine tin key is also supplied and is non-contributory.
Fig. 13.1
(a) Menghini needle set displayed. (b) Menghini needle set assembled for use
The needle is attached to a 20 ml syringe containing 5 ml physiological saline. A skin incision is made with a small blade scalpel and the needle is advanced through the chest wall to the pleura and diaphragm. Two millilitres of saline are injected to clear the needle. With the patient performing the breath-holding manoeuvre, aspiration is applied to the syringe; the needle is rapidly introduced about 4 cm into the liver and immediately withdrawn. The patient is then permitted to breathe normally. The needle is removed from the syringe, the nail removed and the core of liver tissue is gently extruded either onto filter paper or directly into formol saline, using the probe supplied. The contents of the syringe can be flushed through the needle into cytology fixative. If a satisfactory core (>5 mm) is not obtained, two more punctures are permissible at the same procedure. Various modifications of the Menghini system are available. Disposable needles are usual. The Jamshidi needle is supplied with a locking syringe which does not require the operator to maintain traction on the plunger. The Surecut needle is also supplied with a locking syringe, to the plunger of which is attached a retractable trocar which obviates the need for saline injection
13.1.2.2 Tru-Cut Sheathed Needle (Disposable) (Fig. 13.2)
This needle requires more skill in operation, but has become popular partly because of its wide application to other biopsy procedures such as sampling prostate and breast tissue.
Fig. 13.2
(a) Tru-Cut needle closed (top view). (b) Tru-Cut biopsy needle open (side view)
The needle consists of an outer cutting sheath 2 mm in diameter through which is advanced a trocar with a 20 mm sampling groove positioned 10 mm from the tip. There is a choice of length of needle, the most convenient being 114 mm long. After preparation, anaesthesia and skin incision with a scalpel, the needle is advanced to the liver capsule with the trocar retracted. The patient then holds his breath in expiration while the needle is advanced 4 cm into the liver with the trocar fully sheathed. Retraction of the sheath permits a sample of liver to bulge into the trocar sampling groove. The cutting sheath is then fully advanced holding the trocar steady, and the whole needle is removed.
Operators are recommended to practise the sequence of manoeuvres several times before puncturing patients and to consult the manufacturer’s instruction leaflet supplied with each needle. This procedure is an amendment of a previous one, designed to improve safety. Needles must never be reused.
13.1.3 Alternative Techniques
13.1.3.1 Bleeding Tendency
If the prothrombin time is prolonged, vitamin K 10 mg administered IV or IM daily for 3 days may cause it to return to normal. If the prothrombin time remains prolonged and the liver biopsy is mandatory an infusion of 2 units of fresh frozen plasma before and during percutaneous biopsy ensures the safety of the procedure. Similarly, if low platelet counts persist then the transfusion of 6 packs of platelets can be used to cover the procedure. Factor VIII transfusion has been described in patients with haemophilia. It is possible to occlude the needle tract by injecting gelatin sponge.
13.1.3.2 Transvenous Liver Biopsy
This ingenious method uses transjugular hepatic vein catheterization to obtain biopsy samples from patients with a bleeding diathesis. The principle is that any haemorrhage is contained in the patient’s own circulation. The procedure should be reserved for centres with experience of the catheterization technique. There is an appreciable failure rate and biopsy samples tend to be very small.
13.1.3.3 Laparoscopic Liver Biopsy
This is an alternative for the patient with a bleeding tendency, since direct haemostasis can be achieved. It allows targetted biopsy in non-homogenous liver disease and can be specially helpful in macronodular cirrhosis, lymphoma and metastatic disease. Naked-eye diagnosis should be confIrmed by histology, although with experience reliable macroscopic diagnosis of cirrhosis is possible
13.1.3.4 Laparotomy
Liver biopsy at laparotomy is best performed using biopsy needles to avoid spurious conclusions arising from examination of unrepresentative peripheral samples obtained with scissors or scalpel. Ideally, the biopsy should be taken at the first procedure after opening the peritoneum. A laparotomy should never be performed for the sole purpose of obtaining a liver biopsy.
13.1.3.5 Young Children
Percutaneous liver biopsy is feasible in young children using needles 1.2 mm in diameter. One assistant is required to talk to and gently restrain the patient if necessary. Another assistant immobilizes the liver by pressing on the left chest with the right hand, while pushing up the liver with the left hand. The procedure can usually be performed under local anaesthesia, but a general anaesthetic may be required.
13.1.4 Aftercare
Gentle local pressure may be needed to stop oozing of blood. The biopsy wound is covered with an adhesive dressing. The patient is asked to lie as much as possible in the right lateral position for 3–4 h. Pulse and blood pressure are recorded every 15 min for 1 h, then hourly. The patient is warned to expect mild discomfort. If there is a severe pain at the biopsy site, in the epigastrium or right shoulder tip, then an injection of pethidine 25–100 mg IM is given.
Liver biopsy can be safely performed as an out-patient procedure provided that patients can be observed for some hours afterwards. Facilities must be available to allow admission of those who develop significant complications.
13.1.5 Complications
Serious morbidity occurs in about 5% of patients. The most important determining factor is the number of liver punctures. Pain is the most common complication and is usually transient.The major hazards are haemorrhage and bile leakage. Bleeding into the pleura or peritoneum may require transfusion and open suturing. It is diagnosed by a rising pulse and falling blood pressure, without much pain. Bleeding is said to be more common from hepatoma. An intrahepatic haematoma is common and usually of no significance, though it may interfere with subsequent liver imaging techniques.
Bile leakage may occur from an intrahepatic gallbladder. It sometimes occurs from a large duct but this is uncommon if liver biopsy is avoided in patients with extrahepatic cholestasis. Leakage of bile usually causes pain and tachycardia and hypotension may also occur. Any serious bile leak requires early laparotomy, suturing and peritoneal toilet.
The mortality rate of liver biopsy is contentious, but is probably around 1:750 overall. The mortality rate depends on the type of patient undergoing biopsy and can be expected to be higher in patients with metastatic carcinoma. In practice deaths do not seem to be much of a problem in people fit enough to be investigated as outpatients.
13.1.6 Indications
- 1.
Evaluation and monitoring of alcoholic liver disease.
- 2.
Diagnosis of cirrhosis, chronic auto-immune hepatitis, drug jaundice, haemochromatosis, hepatolenticular degeneration, amyloid and sarcoid.
- 3.
Diagnosis of hepatocellular carcinoma.
- 4.
Diagnosis of metastatic carcinoma and lymphoma.
- 5.
Diagnosis of hepatomegaly and splenomegaly.
- 6.
Establishment of the cause of intrahepatic cholestasis.
- 7.
Monitoring the progress of treatment in chronic hepatitis and iron and copper storage diseases.
- 8.
Confirmation of Dubin-Johnson syndrome (constitutional conjugated hyperbilirubinaemia).
- 9.
Estimation of liver enzyme activity, e.g. glucuronyl transferase.
- 10.
Occasionally in the diagnosis of tuberculosis and pyrexia of unknown origin.
13.1.7 Contra-indications to Percutaneous Biopsy
Absolute contra-indications are an uncooperative patient, gross ascites, and suspected hydatid disease, haemangioma or peliosis hepatica.
Relative contra-indications are proved extrahepatic cholestasis and a persistent bleeding tendency.
13.2 Interpretation
13.2.1 Macroscopic Appearance
It is often helpful to inspect the core of tissue which has been obtained. Normal liver is light brown or purple in colour, while biopsies from fatty liver are pale yellow. Metastatic carcinoma may contain white areas, Dubin-Johnson syndrome tissue is black, while in the conjugated hyperbilirubinaemia of the Rotor syndrome it is normal in colour. In cholestasis dark bile, pus and heavy greenish yellow pigmentation may be evident. In cirrhosis the liver appears non-homogeneous and granular, and there is a gritty feel as the biopsy needle is inserted.
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