Domestic liver transplantation has been widely carried out in recent years, and as of 2002, domestic liver transplantation has reached 2000 cases, including more than 1000 cases in the whole year of 2002. As the surgical technique has basically matured, the recent rate after liver transplantation in China has basically approached the foreign level, but there is still a lack of sufficient experience in the medium and long-term management of liver transplantation, and it has not attracted sufficient attention, resulting in the prominent problem that the long-term efficacy of liver transplantation has a large gap compared with that of foreign developed countries.
I. Concept of medium and long-term management
The medium and long-term management after liver transplantation refers to the outpatient management and patient’s self-management after the recipient is discharged from the hospital. However, most of the literature includes patients more than 1 year after transplantation in the category of medium- and long-term management, while long-term survival is generally defined as more than 5 years after transplantation. During this period emphasis should be placed on maintaining close contact between the liver transplant recipient and the transplant center, and the recipient should be able to consult with the transplant center at any time when abnormal manifestations occur, and return to the transplant center for examination and consultation if necessary. It should also be emphasized that liver transplant recipients should visit the hospital for regular checkups.
II. Content of outpatient management in mid- and long-term management
An important element of medium and long-term management after liver transplantation is regular outpatient review and health consultation, which is quite complicated, and is summarized in the following aspects.
1. General medical examination.
Routine checkups should include weight and blood pressure monitoring, routine blood tests, blood electrolyte tests, liver and kidney function tests and blood drug concentration tests, which should be performed at least once a month. In addition, health consultation should be conducted.
2. Screening and census of malignant tumors.
After liver transplantation, due to the combined effect of multiple carcinogenic factors, it may lead to the occurrence of tumors. Long-term immunity may lead to skin cancer, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, cervical cancer, genital tumors and anal canal cancer. Therefore follow-up of recipients should be done looking for early manifestations of these tumors, such as weight loss without release. For male patients older than 40 years old, transrectal ultrasound should be performed annually to rule out prostate tumors, and for patients older than 40 years old, colonoscopy and fecal occult blood test should be performed annually to rule out colorectal tumors. For some high-risk groups, such as preoperative history of tumor, family history of tumor, suffering from long-term infectious intestinal diseases, etc., screening should be conducted in a shorter period of time.
3. Health consultation and medication guidance for common medical problems.
Common medical problems mainly refer to some chronic systemic diseases that may occur in long-term liver transplant recipients, including: renal insufficiency, hypertension, hyperlipidemia, diabetes mellitus, obesity, neurological symptoms and bone diseases. In addition to the above issues, health counseling and related physical and laboratory examinations should be performed for patients with clinical symptoms such as fever and jaundice during follow-up visits.
In the follow-up visit, patients should also be given guidance on medication, including guidance on the use and adjustment of immune agents, guidance on the application of prophylactic antibiotics, and guidance on the interaction between different drugs. In addition, liver transplant patients should all wait to receive vaccinations consistent with their age, but active vaccines should be used.
Common complications and management in mid- and long-term management
1. Chronic graft loss of function.
It is now believed that chronic reactions are not only related to sexual immunity, but also more closely related to non-sexual tissue damage, hence the term chronic graft incompetence. Some authors believe that chronic graft incompetence is a comprehensive group of graft reactions to injury, mainly manifested as bile duct disappearance syndrome, whose mechanism of occurrence has not yet been elucidated, and there is no effective drug treatment countermeasures.
As a clinician, we can only focus on prevention at present. It is believed that the following factors may be related to chronic graft loss, including: frequent acute reactions, side effects of immune medications, marginal donor organs, ischemia-reperfusion injury, CMV infection, so these conditions should be prevented as much as possible, and treated as early as possible once they occur.
2. Recurrent diseases.
In liver transplant patients, part of the recipient’s liver diseases are metabolic disorders, which can generally be cured by liver transplantation without recurrence of old diseases. In contrast, patients with viral hepatitis, autoimmune liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis who undergo liver transplantation are at risk for recurrence of old disease.
Recurrence of hepatitis B and C can lead to loss of function of the transplanted liver. Severe hepatitis B infection in cirrhotic transplanted livers is an important cause of transplant failure. 58% of HBeAg-negative/HBVDNA-negative patients have recurrence of hepatitis B after surgery, while HbeAg-positive/HBVDNA-positive patients have recurrence in almost 100% of cases after surgery. Recurrence often occurs 1 year after liver transplantation and can progress to cirrhosis or even to hepatocellular carcinoma within 2-3 years.
The prognosis of patients with recurrent hepatitis B after liver transplantation is not yet satisfactory. Currently, it is believed that hepatitis B virus immunoglobulin, interferon and the anti-hepatitis B virus drugs Famciclovir and Lamivudine can reduce the replication of HBV, reduce its recurrence or turn HBVDNA negative. Hepatitis B virus immunoglobulin has reduced the rate of HBV reinfection and morbidity and mortality. The long-term combination of hepatitis B immunoglobulin and lamivudine now significantly improves graft function and patient long-term rates.
Additional factors that affect the outcome of hepatitis B liver transplantation include.
Compound staining, cross staining and pre-transplant HBVDNA positive and HBeAg positive factors. Early withdrawal of hormones has been reported to reduce the recurrence of hepatitis B virus. For end-stage liver disease due to hepatitis C, liver transplantation is the only effective treatment. The 5-year rate of hepatitis C decompensated cirrhosis is 50%, which can be increased to 70%-80% after liver transplantation. However, the postoperative relapse rate is >95%, mainly due to viremia, and does not affect the 5-year rate after transplantation. There is no effective antiviral therapy to eliminate its recurrence, although there is information that interferon may be able its activity in some patients, but the treatment outlook is not yet optimistic.
Other recurrent diseases include recurrence of malignancy and recurrence of alcoholic liver disease. In the early stages of liver transplantation, there was great enthusiasm for the use of transplantation to treat malignancies of the liver, but in situ liver transplantation is currently not considered to be effective for liver tumors that cannot be surgically removed, and the overall results have been disappointing. Recurrence rates of hepatocellular carcinoma after liver transplantation have been reported to be 39%-67%, and survival rates at 3 years after transplantation are 15%-38%, with recurrence of liver cancer being the main cause of poor outcomes.
Most recurrences of hepatocellular carcinoma are found within 1 year-2 years after liver transplantation. The common sites of recurrence are in the liver and lung. However, recurrence after liver transplantation for small liver cancers is rare and the rate is high. In the country, alcoholic liver disease is a common end-stage liver disease and the most prominent indication for liver transplantation, with better transplantation results compared to other non-alcoholic benign liver diseases. However, relapse of alcoholic liver disease is also a major problem, and it is speculated that 10-15% of patients will indulge in alcoholism again.
3. Renal insufficiency.
Long-term surviving liver transplant recipients often have reduced glomerular filtration capacity and mildly elevated serum creatinine levels. This decline in renal function often occurs soon after surgery, but can often be maintained for many years and rarely progresses to end-stage renal disease. The exact cause of the decrease in renal function is not known, but it is likely to be related to the use of immunologic agents. Serum creatinine levels should be rechecked monthly after liver transplantation, and most transplant centers often adjust the blood levels of immune agents to reduce the nephrotoxicity of immune agents when serum creatinine levels change.
Also some drugs that may produce nephrotoxicity should be avoided as much as possible. These include aminoglycosides and non-steroidal anti-inflammatory agents that can increase the nephrotoxicity of cyclosporine A and FK506 and should be avoided. Other drugs, such as amphotericin and amphotericin B, should also be used with caution.
4. Hyperlipidemia and other cardiovascular diseases.
Many recipients have high risk factors for cardiovascular disease, such as men >45 years old >55 years old women, high-fat diet, smoking, obesity, hypertension and family history, etc. About 40% of recipients may develop hyperlipidemia after surgery. Regular routine lipid testing should be performed, and when elevated lipids are found, non-pharmacological treatment, including strengthening physical exercise, diet control, and smoking cessation, should be taken first. ,
Pravastatin may be the best choice when patients present with more severe hyperlipidemia, but it may cause appetite changes and changes in lifestyle habits. The first-line drug for the treatment of post-transplant hypertension is a calcium channel negative blocker such as idebenone or nifedipine.
5. Nutritional problems.
40-70% of liver transplant patients will be overweight or obese after 1 year postoperatively. Dietary measurements and health pattern monitoring should be performed continuously after liver transplantation, and the blood concentration of corticosteroids should be reduced or even withdrawn for those who are excessively obese. Some other patients will develop malnutrition after transplantation, especially those on FK506, which causes loss of appetite. However, in patients with weight loss, the occurrence of malignancy should first be ruled out.
6. Depression and other problems.
There are some recipients, especially in patients with multiple postoperative complications, who may develop depression. Also some patients become depressed because they are overly worried about recurrent postoperative liver disease (e.g., viral hepatitis).
The development of depression often leads to alcohol and drug dependence. For patients suspected of having depression, once organic lesions are excluded, relevant antidepressant treatment should be administered, including regular follow-up, psychological guidance, psychological counseling for those who are inclined, and application of antidepressant drugs, but attention should be paid to drug interactions.
7. Other.
Bone loss and its complications often occur after liver transplantation, especially in patients with alcoholic liver disease and cholestatic liver disease liver transplantation is more frequent after surgery. The best predictor of bone disease after liver transplantation is the severity of bone loss before transplantation, with a continuous decrease in total bone mass for 6 months after liver transplantation and subsequent gradual improvement.
In this group of patients, hormonal dosage should be kept as low as possible, while timely supplementation of calcium and vitamin D is often necessary, especially in patients with cholestasis. In addition, hormone replacement therapy is reasonable and safe for postmenopausal liver transplant patients.