LIVER TRANSPLANTS

Indications for transplant
Liver transplantation has now become a successful treatment for many chronic liver conditions and is also used in the treatment of fulminant hepatic failure.
The range of indications has steadily increased as surgical techniques have developed and immunosuppression has improved . The majority of hepatic transplants (80%) are still performed in patients with cirrhosis and primary cholestatic disease. The 5-year survival rate is between 65 and 90%.32,33 This is highly dependent upon both the primary disease and upon the clinical state of the patient.
Currently, seven centres in the UK perform liver transplants, totalling around 700 patients per year.
This figure has remained relatively stable for some time and is dependent upon the availability of donor organs. Worldwide, the most common cause for liver transplantation is hepatitis C. The indications for transplant are now many and varied and the number of absolute contraindications continues to dwindle,
including AIDS and extrahepatic malignancy. Transplantation in patients with malignant liver disease has a poorer prognosis with a lower 5-year survival. However, the presence of small HCCs in patients with chronic liver disease is not a contraindication, and tumour recurrence is uncommon in these patients. Patients with larger HCCs (> 3 cm) and those with cholangiocarcinoma have a higher rate of recurrence post-transplant. and are generally not considered for transplantation.
Table 4.7 Indications for liver transplantation
Chronic cholestatic disease
—PBC, PSC
Cirrhosis
—from hepatitis, alcoholic liver disease or other causes
(without malignancy)
Biliary atresia
—usually in children who have developed SBC
Malignancy
—patients with HCC associated with cirrhosis, provided
the lesion is small (< 3 cm) and solitary
Budd–Chiari syndrome
—non-malignant occlusion of the hepatic veins,
especially total venous occlusion and/or patients with
cirrhosis resulting from BCS
Fulminant hepatic failure
—due to drug (usually paracetamol) overdose, acute
hepatitis, BCS, Wilson’s disease or massive hepatic
trauma (an acute situation requiring immediate
transplant if a suitable donor is found)
Others
—rarely, transplant is undertaken for benign lesions
such as PCD, adenoma or large haemangiomas
NB:
PBC = primary biliary cirrhosis, PSC = primary sclerosing cholangitis,
SBC = secondary biliary cirrhosis, BCS = Budd–Chiari syndrome,
PCD = polycystic disease
Table 4.8 Contraindications to liver transplant
Absolute
—extrahepatic malignancy
—active extrahepatic sepsis
—severe cardiopulmonary disease
—AIDS
—inability to comply with regular postoperative drug
treatment
Relative—age > 65, particularly if related to poor general
health
—moderate cardiopulmonary disease
—PV thrombosis
—active alcoholism or drug abuse
—previous complex hepatic surgery
—multiple or large focal hepatic malignancies (e.g.
cholangiocarcinomas associated with PSC)

AIDS = aquired immunodeficiency syndrome, PV = portal vein

Preoperative assessment LIVER TRANSPLANTS
The ultrasound scan is one of many investigations leading up to transplantation. The diagnosis of liver pathology often uses ultrasound scanning as a
first line, augmented by histology and additional cross-sectional imaging. The role of ultrasound includes contributing to, or confirming, the initial diagnosis, assessing the degree of severity and associated complications of the disease and providing guidance for biopsy. Animportant objective is also to exclude patients for whom liver transplant is not feasible, or of little benefit (Table 4.8), for example those with extrahepatic malignant disease.
The preoperative scan includes all the features of any abdominal ultrasound survey, with the emphasis on assessing the complications of the disease, depending upon the initial diagnosis. In particular, the sonographer should look for:
● Portal vein thrombosis: this may be a contraindication to transplant if it is extensive, or unable to be effectively bypassed by the surgeon.
● Any of the features of portal hypertension associated with chronic liver disease (see above).
● Focal liver lesions which may represent malignancy. These may require the administration of ultrasound contrast agents, or further imaging to characterize, such as MRI. An HCC greater than 3 cm in diameter has an 80% chance of recurrence post-transplant. If under 2 cm and solitary, this is likely to be cured. Check the size, number and local spread of disease.
● It is useful to document the spleen size as a baseline for postoperative comparisons.
● Extrahepatic malignancy, in cases with an initial diagnosis of carcinoma.
● Degree and scope of vascular thrombosis in cases of BCS.
● Any incidental pathology which may alter the management plan. Doppler ultrasound is, of course, essential in assessing the patency and direction of blood flow of the portal venous system, the hepatic veins, IVC and main hepatic artery. It may occasionally be possible to demonstrate arterial anomalies. While
large numbers of patients are considered for transplant and undergo ultrasound assessment, the majority of these will never actually be transplanted.
This factor has numerous implications for resources when setting  up a transplant ultrasound service.
Operative procedure LIVER TRANSPLANTS
Most transplants are orthotopic, that is the diseased liver is removed and replaced by the donor organ, as opposed to heterotopic, in which the donor
organ is grafted in addition to the native organ (like most kidney transplants). If the patient suffers from extensive varices, which may bleed, the removal of the diseased  Donor livers which are too large for the recipient, for example in small children, may require cutting down to reduce the size. There is an
increasing trend towards a ‘split liver’ technique, in which the donor liver is divided to provide for two recipients. The lack of donors has also led to the
development of living-related donor transplantation for paediatrics.
The transplant requires five surgical anastomoses:
● suprahepatic vena cava
● infrahepatic vena cava
● hepatic artery (either end-to-end, or end-toside to aorta)
● PV
● CBD (the gallbladder is removed).
IOUS is useful for assessing the size and spread of intrahepatic neoplastic growths and to assess vascular invasion in the recipient. Mapping of the hepatic vascular anatomy in living-related donors is also feasible using IOUS. IOUS with Doppler is also useful for assessing the vascular anastomoses and establishing if portal venous and hepatic arterial flow are adequate.
Postoperative assessment LIVER TRANSPLANTS
Ultrasound plays a key role in the postoperative monitoring of liver transplant patients. Numerous complications are possible (Table 4.9) and many of
these can be diagnosed with ultrasound. The operation is generally followed by ciclosporin immunosuppression. Blood levels of ciclosporin are a
closely monitored balancing act; too low and the graft may reject, too high and the toxic effects of the drug may affect the kidneys.
Liver function is biochemically monitored for early signs of complications. Elevated serum bilirubin, alkaline phosphatase and/or aminotransferase
levels are present with most types of graft dysfunction or complication and are investigated first with ultrasound.
Renal dysfunction is a further recognized complication following transplant. This can be due to various causes, including ciclosporin nephrotoxicity,
intraoperative hypotension or preoperative renal failure.
TABLE. 4.9 Postoperative liver transplant complications
Infection
—hepatic abscess/general abdominal infection leading to sepsis
Vascular
—anastomotic leaks → haematoma
—thrombosis or stenosis → ischaemia/infarction
Biliary
—bile duct stricture or stenosis leading to dilatation
—bile leak → biloma
Rejection
—acute episodes are common in up to 80% of patients in the first 2 weeks and are of variable severity
Other medical complications
—neurological
—renal dysfunction
Recurrence of original disease
—hepatitis
—cholangiocarcinoma or hepatocellular carcinoma
—Budd–Chiari syndrome
—PSC
Post-transplant lymphoproliferative disorder (PTLD)—more common in children, PTLD is more usually associated with immunosuppressions, occurring within the first year of transplant.
Postoperative ultrasound appearances LIVER TRANSPLANTS
The vessels and vascular anastomoses These are potential sites of complication in terms of thrombosis, stenosis, occlusion or leakage. The hepatic artery is vital to graft success as it is the sole vascular supply to the biliary system. Most hepatic artery occlusions occur relatively soon after operation, before a good collateral supply is able to be established.
A blocked hepatic artery quickly results in ischaemia with resultant hepatic necrosis and is therefore treated as an emergency requiring surgical
intervention and, frequently, retransplant. Taken in context with the clinical picture, the patient may proceed immediately to surgery if the ultrasound
diagnosis of occlusion is confident. If doubt exists, MRI or X-ray angiography may be performed. Ensure the artery is scanned intercostally to maintain a low vessel-to-beam angle, and that the Doppler sensitivity and filter controls are set for low velocities if arterial flow is not found. Hepatic artery thrombosis or stenosis can lead to bile duct necrosis, causing bile leaks and abscesses, or areas of infarction within the liver tissue. Hepatic artery stenosis/thrombosis is still a relatively common post-transplant complication in up to 12% of adult patients. Colour Doppler ultrasound detects between 50% and 86% of total occlusions and angiography is still considered the gold standard although ultrasound continues to increase its clinical value here. The administration of ultrasound contrast media, whilst potentially useful for detection of flow, is rarely necessary in practice.
Stenosis of the artery at the site of anastomosis is detected by examining the Doppler spectrum (Fig. below). The systolic upstroke tends to be delayed (‘tardus parvus’ pattern) downstream of the stenosis;37 the acceleration time is increased (over 0.08 seconds) and the resistance index decreased (less than 55) in many cases. Both or either of these indices may be affected, giving a sensitivity and specificity of 81% and 60% for the diagnosis of hepatic artery stenosis with Doppler. The appearance of the hepatic artery waveform immediately postoperatively is often one of a small spike with no EDF. This is not a significant finding and will usually develop into the more familiar waveform with forward EDF by 48 hours after transplantation. The PV anastomosis is readily demonstrated at the porta. The waveform invariably shows turbulence associated with the anastomotic site (Fig. below), as the diameters of the donor and recipient veins invariably differ. This is not significant in itself but can indicate a clinically significant stenosis when accompanied by high velocities of greater than 100 cm/sec (Fig. below). PV stenosis also causes a steadily increasing spleen size, which is why it is important to have a baseline measurement of the spleen. PV thrombosis should only be diagnosed using the correct Doppler settings (low pluse repetitions frequency and optimum colour gain) and at an angle as near parallel to the beam as possible. In the absence of colour flow, power Doppler may be helpful in confirming thrombosis, as it is less angle-dependent, and contrast may be used to increase the level of confidence.
image
Ultrasound images MHA in a liver transplant demonstrated
on power Doppler, lying anterior to the MPV
image
Normal
hepatic artery (HA) waveform post-transplant

imageUltrasound images 1 month
later, the systolic slope shows a tardus parvus pattern.
HA stenosis was confirmed with angiography.
image
The portal vein in a liver transplant
demonstrates a very turbulent waveform because of the surgical
anastomosis. This is not usually a significant finding
image
Ultrasound images MPV stenosis. A high-velocity jet is seen through the stenosis (arrow)
at the site of the anastomosis. The spectral Doppler waveform
exceeded the Nyquist limit at this point
image
ultrasound images The site of anastomosis in the IVC in a
liver transplant.
image
Ultrasound images An area of infarction in a liver transplant
It is also possible to have a blocked main PV with patent intrahepatic PVs, due to collateral formation.  The IVC infrahepatic anastomosis is also readily
seen on ultrasound (Fig. 4.32). Because of the  near-perpendicular angle of the IVC to the beam it is difficult to assess blood flow velocity in the IVC.
Power Doppler is helpful in confirming patency in technically difficult cases as it is angle-independent. Thrombosis in the IVC is a relatively rare complication
of transplants, accounting for fewer than 3% of patients. If the transplant has been performed for BCS, pay particular attention to the hepatic veins, which
show a tendency to re-thrombose in some patients.
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