Indications for liver biopsy
Percutaneous liver biopsy has a small but
inherent risk even in the most experienced
hands, and it should therefore only be performed
when the benefits of knowing the
histology outweigh the risks to the patient (in
terms of altering treatment or defining disease
outcome). These benefits should be continually
re-evaluated as new treatment options
become available such as has occurred with the
new antiviral therapies in viral hepatitis and in
liver transplantation.
Acute hepatitis of unknown etiology, including
possible drug related hepatitis, has long
been an indication for per cutaneous liver
biopsy, but liver biopsy in typical acute viral
hepatitis is usually not necessary. The usefulness
of liver biopsy in chronic viral hepatitis
was once hotly debated; however, with the
advent of new antiviral therapies there is no
doubt of the value of histology in assessing
those patients who will benefit from treatment
and assessing their response to it.
Patients with chronic hepatitis C virus infection
as determined by a positive serum
polymerase chain reaction test, who are being
considered for antiviral therapy should undergo
liver biopsy. Liver biopsy should probably
be undertaken even if the patient has normal
aminotransferases as it has been reported
that up to 50% of patients with active disease
have a normal serum alanine aminotransferase.
A liver biopsy sample is useful in
this instance in allowing an assessment of the
Hepatitis Activity Index (a necroinflammatory/
fibrosis scoring system) and to identify
confounding factors such as alcoholic liver disease
and haemochromatosis. Unfortunately,
histology of a single liver biopsy sample and the
monitoring of aminotransferases are poor predictors
of disease progression. Consequently,
repeat samples taken every two or three years
may be needed to assess disease progression
and prognosis.
In patients with raised serum ferritin or
where disorders of copper metabolism are suspected,
liver biopsy provides material for
measurement of iron and copper within the
liver parenchyma, although genetic analysis
may help to differentiate genetic haemochromatosis
from other causes of iron overload.
Culture of biopsy material can help in the
diagnosis of infections such as tuberculosis.
The need for liver biopsy in patients with
intrahepatic cholestasis from primary biliary
cirrhosis (PBC) and primary sclerosing
cholangitis (PSC) is more controversial.On the
one hand, the discovery that a persistentlyraised E2-antimitochondrial antibody (AMA)
confirms a diagnosis of PBC (even if patients
have no other signs or symptoms of PBC)
means that a liver biopsy in the early stages of
typical PBC (i.e., a middle aged woman with
cholestasis) may be unnecessary.On the
other, for more advanced disease liver biopsy
may be useful in accurately staging the disease.
The diagnosis of PSC related cholestasis is
usually made at endoscopic retrograde cholangiopancreatography
(ERCP) or MRI cholangiography,
and diagnostic histological features in
needle biopsy specimens are often not seen.
Liver biopsy is often useful in the diagnosis
and management of patients with alcohol
related liver diseases, as well as helping in the
diagnosis of infections such as tuberculosis.
Liver biopsy still remains part of the investigation
of pyrexia of unknown origin and is also
useful in the diagnosis of storage disorders.
Liver biopsy is often used in the investigation
of abnormal liver enzymes but this must be
taken in context, tempered by the results of
other routine investigations, and take into
account the patient’s details. For example, the
investigation of an isolated raised alkaline
phosphatase will be very different in an 80 year
old compared with a 25 year old. Raised
ã-glutamyl transpeptidase (GGT) activities
have been shown to be a sensitive marker of
alcohol misuse; however, an isolated increase in
GGT is not associated with major liver pathology
and is therefore not an adequate indication
on its own for liver biopsy.
The role of percutaneous liver biopsy in the
diagnosis of focal liver lesions depends largely
upon the clinical picture. In most patients with
malignant hepatocellular carcinoma ultrasound
scanning, CT, and measurement of
serum á-fetoprotein will allow a diagnosis to be
made (in the context of a space-occupying
lesion in a cirrhotic patient). Similarly, a patient
with a history of colonic resection for neoplasia
who presents with a solitary lesion in the liver
associated with raised serum carcinoembryonic
antigen, may not require a biopsy of the lesion
to make the diagnosis of a potentially resectable
metastasis. Liver biopsy also carries a
documented risk of seeding tumors down the
biopsy track.The magnitude of this risk is
currently unknown. Modern imaging techniques
can also help to define other types of
focal hepatic lesions such as haemangiomata
and focal nodular hyperplasia. In these situations,
some experts believe that the risk of
bleeding after biopsy of a malignant tumour is
greatest when the tumour is superficial and so
recommend traversing normal liver before
sampling tumour tissue. Fine needle aspiration
biopsy may be a safer option if material for histological
examination is required in the case of
a suspected angioma.
The use of liver biopsy after liver transplantation
is increasing, and policies on histological
monitoring vary between liver transplant units.
Some units perform routine biopsies on day 7
after transplant to assess acute rejection,
whereas others do annual review biopsies at
which abnormalities are frequently seen.
Liver biopsy is also useful in the diagnosis ofinvasive cytomegalovirus infection and in
assessing recurrent disease.
Using liver biopsy in the context of research
is controversial but has undoubtedly given
invaluable information in the past in such areas
as hepatitis C disease progression and the
development of new drugs.
We feel that these
biopsies should be performed in the context of
a clinical trial and where approval has been
given by the local research ethics committee. In
circumstances where the patient will derive no
potential benefit from the procedure, and will
thus only accrue the risks of that procedure, the
patient should be fully aware of this and give
written consent.
inherent risk even in the most experienced
hands, and it should therefore only be performed
when the benefits of knowing the
histology outweigh the risks to the patient (in
terms of altering treatment or defining disease
outcome). These benefits should be continually
re-evaluated as new treatment options
become available such as has occurred with the
new antiviral therapies in viral hepatitis and in
liver transplantation.
Acute hepatitis of unknown etiology, including
possible drug related hepatitis, has long
been an indication for per cutaneous liver
biopsy, but liver biopsy in typical acute viral
hepatitis is usually not necessary. The usefulness
of liver biopsy in chronic viral hepatitis
was once hotly debated; however, with the
advent of new antiviral therapies there is no
doubt of the value of histology in assessing
those patients who will benefit from treatment
and assessing their response to it.
Patients with chronic hepatitis C virus infection
as determined by a positive serum
polymerase chain reaction test, who are being
considered for antiviral therapy should undergo
liver biopsy. Liver biopsy should probably
be undertaken even if the patient has normal
aminotransferases as it has been reported
that up to 50% of patients with active disease
have a normal serum alanine aminotransferase.
A liver biopsy sample is useful in
this instance in allowing an assessment of the
Hepatitis Activity Index (a necroinflammatory/
fibrosis scoring system) and to identify
confounding factors such as alcoholic liver disease
and haemochromatosis. Unfortunately,
histology of a single liver biopsy sample and the
monitoring of aminotransferases are poor predictors
of disease progression. Consequently,
repeat samples taken every two or three years
may be needed to assess disease progression
and prognosis.
In patients with raised serum ferritin or
where disorders of copper metabolism are suspected,
liver biopsy provides material for
measurement of iron and copper within the
liver parenchyma, although genetic analysis
may help to differentiate genetic haemochromatosis
from other causes of iron overload.
Culture of biopsy material can help in the
diagnosis of infections such as tuberculosis.
The need for liver biopsy in patients with
intrahepatic cholestasis from primary biliary
cirrhosis (PBC) and primary sclerosing
cholangitis (PSC) is more controversial.On the
one hand, the discovery that a persistentlyraised E2-antimitochondrial antibody (AMA)
confirms a diagnosis of PBC (even if patients
have no other signs or symptoms of PBC)
means that a liver biopsy in the early stages of
typical PBC (i.e., a middle aged woman with
cholestasis) may be unnecessary.On the
other, for more advanced disease liver biopsy
may be useful in accurately staging the disease.
The diagnosis of PSC related cholestasis is
usually made at endoscopic retrograde cholangiopancreatography
(ERCP) or MRI cholangiography,
and diagnostic histological features in
needle biopsy specimens are often not seen.
Liver biopsy is often useful in the diagnosis
and management of patients with alcohol
related liver diseases, as well as helping in the
diagnosis of infections such as tuberculosis.
Liver biopsy still remains part of the investigation
of pyrexia of unknown origin and is also
useful in the diagnosis of storage disorders.
Liver biopsy is often used in the investigation
of abnormal liver enzymes but this must be
taken in context, tempered by the results of
other routine investigations, and take into
account the patient’s details. For example, the
investigation of an isolated raised alkaline
phosphatase will be very different in an 80 year
old compared with a 25 year old. Raised
ã-glutamyl transpeptidase (GGT) activities
have been shown to be a sensitive marker of
alcohol misuse; however, an isolated increase in
GGT is not associated with major liver pathology
and is therefore not an adequate indication
on its own for liver biopsy.
The role of percutaneous liver biopsy in the
diagnosis of focal liver lesions depends largely
upon the clinical picture. In most patients with
malignant hepatocellular carcinoma ultrasound
scanning, CT, and measurement of
serum á-fetoprotein will allow a diagnosis to be
made (in the context of a space-occupying
lesion in a cirrhotic patient). Similarly, a patient
with a history of colonic resection for neoplasia
who presents with a solitary lesion in the liver
associated with raised serum carcinoembryonic
antigen, may not require a biopsy of the lesion
to make the diagnosis of a potentially resectable
metastasis. Liver biopsy also carries a
documented risk of seeding tumors down the
biopsy track.The magnitude of this risk is
currently unknown. Modern imaging techniques
can also help to define other types of
focal hepatic lesions such as haemangiomata
and focal nodular hyperplasia. In these situations,
some experts believe that the risk of
bleeding after biopsy of a malignant tumour is
greatest when the tumour is superficial and so
recommend traversing normal liver before
sampling tumour tissue. Fine needle aspiration
biopsy may be a safer option if material for histological
examination is required in the case of
a suspected angioma.
The use of liver biopsy after liver transplantation
is increasing, and policies on histological
monitoring vary between liver transplant units.
Some units perform routine biopsies on day 7
after transplant to assess acute rejection,
whereas others do annual review biopsies at
which abnormalities are frequently seen.
Liver biopsy is also useful in the diagnosis ofinvasive cytomegalovirus infection and in
assessing recurrent disease.
Using liver biopsy in the context of research
is controversial but has undoubtedly given
invaluable information in the past in such areas
as hepatitis C disease progression and the
development of new drugs.
We feel that these
biopsies should be performed in the context of
a clinical trial and where approval has been
given by the local research ethics committee. In
circumstances where the patient will derive no
potential benefit from the procedure, and will
thus only accrue the risks of that procedure, the
patient should be fully aware of this and give
written consent.
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