Volume 68 - 2005 - Fasc.3 - Symposium
Practical use of hepatitis C and B molecular tools : Belgian Guidelines
This article discusses the use of virologic assays in the diagnosis and management of hepatitis C virus (HCV) and hepatitis B (HBV)infection. The use of virologic tests has become essential in the management of HCV and HBV infection to diagnose viral infection, guide treatment decisions, and assess the virologic response to antiviral therapy. The continuing development of test systems accompanied by new antiviral drugs and novel therapeu- tic approaches should lead to an optimization of the treatment of HCV infection.
Molecular methods for viral testing have become an integral part of the diagnostic and therapeutic management of infections with hepatitis C virus (HCV) and hepatitis B virus (HBV). (Acta gastroenterol. belg., 2005, 68, 308-313).
The management of patients with mild hepatitis C
Infection with the hepatitis C virus (HCV) represents an impor- tant public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepati- tis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver dis- ease. However, the identification of these patients with mild hepati- tis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are per- sistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probabili- ty of response and the motivation of the patient. (Acta gastro- enterol. belg., 2005, 68, 314-318).
The first liver transplantation in Belgium, and there- by one of the first in Europe, was performed in Leuven by the team of Professor Kestens on June 18, 1969.
The liver transplantation program of the Cliniques universitaires Saint-Luc in Brussels actually started on February 5th 1984 when a young man with end-stage liver failure due to hepatitis B viral infection was trans- planted successfully.
Several more patients, transplanted during the same year, are still alive and well twenty years later, with a good functioning graft.
Stepwise minimization of the immunosuppressive therapy in pediatric liver transplantation A conceptual approach towards operational tolerance (*)
The evolution of immunosuppression in pediatric liver trans- plantation has been characterized by a steady reduction of the immunosuppressive load, including removal of anti-lymphocyte antibodies, with the aim to reduce the incidence of EBV-related post-transplant lymphoproliferative disorders. Acute rejection rates were studied retrospectively over two decades of pediatric liver transplantation, according to the successive immunoprophy- lactic regimens. 318 primary pediatric liver transplant recipients, included between 1984 and 2004 in successive prospective trials, were analyzed, with respect to the impact of the immunosuppres- sive protocol on acute rejection occurence. A progressive decrease of rejection incidences was observed, which corresponded to reduced immunosuppressive load and to transplant eras. Such trend might be related to changing approaches towards acute rejection histology and therapy by transplant clinicians, but also to the stepwise minimization of immunosuppressive protocols, putatively enhancing graft acceptance. We hypothesize that the recent population of liver transplant recipients with low immuno- suppression might be more suitable for progressive immunosup- pression withdrawal trial, with the aim to reach ultimately opera- tional tolerance. (Acta gastroenterol. belg., 2005, 68, 320-322).
Long-term medical complications and quality of life in adult recipients surviving 10 years or more after liver transplantation
Background and study aims : Little information is available about long-term results after adult liver transplantation. This study analyses long-term medical complications, changes of immunosuppression, recurrence of primary disease and quality of life 10 years after liver transplantation.
Material and methods : During the period February 1984 - April 1994, 324 LT were performed in 282 adults (>15 years). One hun- dred forty-seven (52%) patients survived more than 10 years. Data regarding health status of 103 patients exclusively followed-up in our institution were analyzed.
Results : Actual 1, 5, 10 years survival rates of the 282 recipients were 76.6%, 64.9% and 52% respectively. Forty eight (46.6%) of the 103 studied patients had normal liver tests in their tenth year of the follow-up. Seventy-one (69%) patients were on a CyA, TAC or MMF monotherapy ; 31 (30%) patients had CyA levels of less than 100ng/ml. Forty five patients had recurrent allograft disease. Twenty-four (40.6%) of 59 liver biopsy available at 10th year were normal. Thirty five (34%) patients developed chronic renal failure ; nine (8.7%) of them had end-stage renal disease. New onset hypertension (> 140/100 mmHg) developed in 49 (47.6%) patients ; fourteen (13,6%) developed diabetes (glucose blood level > 140 mg/dl) and twenty five (24.2%) patients had serious cardiovascu- lar events. Thirteen (12.6%) patients had a BMI>28 and thirty six (35%) patients had elevated serum cholesterol (> 220 mg/dl). Cataract was present in 8 (7,7%) patients. De novo malignancy developed in 23 (22.3%) patients. One patient each developed nasopharyngeal lymphoproliferative disease and myeloma. Quality of life of this patient cohort was excellent as shown by a Karnofsky score of more than 80% in 96.6% of patients.
Conclusion : The high rate of medical complications and espe- cially of malignant tumours in this long-term follow-up study indi- cate that further optimization and especially minimization of immunosuppressive therapy as well as development of newer ther- apies in order to prevent recurrent allograft diseases are the pri- ority for the future development of transplant medicine. (Acta gastroenterol. belg., 2005, 68, 323-330).
Recurrence of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation
Liver transplantation (LT) is the standard therapeutic approach for the treatment of end-stage acute and chron- ic autoimmune liver disease as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary scle- rosing cholangitis (PSC).
Results of liver transplantation in these indications are good with a patient survival after LT at 5 years of 85%.
However several series have reported a possible recurrence of primary autoimmune liver disease after liver transplantation. Concerning all these three autoim- mune liver diseases, recurrence of the disease on the graft may have multiple clinical, biochemical, histologi- cal and radiological expression influenced by different factors as the diagnostic methods used, the degree of immunosuppression and the genetic background of the recipient.
We would like with this overview to describe the dif- ferent pattern of recurrence of these autoimmune liver disease, their potential influence on the liver graft and their therapeutic management.
Recurrent allograft disease : viral hepatitis
Viral hepatitis is the leading indication for liver transplantation (LT) in the majority of transplant centers. Post-transplantation outcome in these patients largely depends on the prevention of allograft reinfection. In contrast to hepatitis B where excellent results have been achieved following the implementation of effec- tive measures to prevent HBV (1,2), recurrent hepatitis C is an increasing problem facing liver transplant hepatologists and sur- geons (3-5). HBV recurrence is effectively contained by the use of hepatitis B inmunoglobulins with antivirals (6,7). Unfortunately, no effective prophylactic therapy is available for hepatitis C so that recurrent hepatitis C occurs almost invariably. Progression to severe allograft fibrosis is often rapid. Current antivirals, includ- ing peg-interferons, are limited by substantial toxicities that com- promise their efficacy (3,8). Hence, it is not surprising that although some improvements have been made in the treatment of recurrent hepatitis C, a substantial proportion of HCV-infected patients develop recurrent allograft end-stage liver disease leading to a decrease in graft survival, an increase in the need for re-trans- plantation, and ultimately, a decrease in patient survival (4,5). (Acta gastroenterol. belg., 2005, 68, 337-346).
Noncompliance with immunosuppressive regimen in organ transplantation : Is it worth worrying about ?
Transplantation is a valuable option for end stage kid- ney, heart and liver disease (e.g. RTX : 1-2 ; e.g. HTX : 3 ; e.g. LTX : 4-5). However, transplantation needs to be regarded as chronic condition. According to the World Health Organization (WHO), 'chronic diseases' are defined as : "diseases which have one or more of the fol- lowing characteristics : they are permanent, leave resid- ual disability, are caused by non-reversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long peri- od of supervision, observation or care" (6).
Transplantation okay - Psyche okay ? Reflections on psychosomatics in the field of organ transplantation
Transplantation puts a large burden on patients' psyche, before and after the operation. Psychosomatic care implicates helping patients to take a firm decision in favour of a new organ, of a new life. Incorporation of the graft, efficient doctor-patient-relations, pregnancy and sexuality, everything is possible but crucial to many patients. Psychosomatic knowledge and specified consulting help them and their families and even the doctors and nurses to cope with overwhelming emotions, fear and a lifelong danger of loosing the organ. Transplantation means crossing borders, going into unknown psychic regions. And the recent rapid development of living liver transplantation does not facilitate things. (Acta gastroenterol. belg., 2005, 68, 353-357).
Prospects of the use of hepatic cells for extracorporeal liver support
Hybrid extracorporeal liver support is an option to assist liver transplantation therapy. An overview on liver cell bioreactors is given and our own development is described. Furthermore, the prospects of the utilization of human liver cells from discarded transplantation organs due to steatosis, cirrhosis or traumatic injury, and liver progenitor cells are discussed. Our Modular Extracorporeal Liver Support (MELS) concept proposes an inte- grative aproach for the treatment of hepatic failure with appro- priate extracorporeal therapy units, tailored to suit the actual clin- ical needs of each patient. The CellModule is a specific bioreactor (charged actually with primary human liver cells, harvested from human donor livers found to be unsuitable for transplantation). The DetoxModule enables albumin-dialysis for the removal of albumin-bound toxins, reducing the biochemical burden of the liver cells, and replacing the bile excretion of hepatocytes in the bioreactor. A Dialysis Module for continuous veno-venous hemofil- tration can be added to the system if required in hepato-renal syn- drome. (Acta gastroenterol. belg., 2005, 68, 358-368).
Extension of the adult hepatic allograft pool using split liver transplantation
Background : The ever increasing number of, especially, adults waiting for a liver transplantation necessitates to develop tech- niques allowing to extend the available donor liver pool.
Materials and Methods: Between November 1988 and December 2004, 37 (6.6%) of 559 adults underwent split liver transplantation at Saint-Luc Hospitals. There were 36 were right and one left split procedures ; 27 split grafts were obtained ex-situ and 10 in-situ. Results of these series are analysed and compared to literature data of split liver transplantation.
Results : Three and 12 months patient survival rates were 89.2% and 78.4% respectively. Five years actuarial patient sur- vival was 75.7%. Early (< 3 months) and late (> 3 months) mor- tality rates were 10.8% (4 pat.) and 21.6% respectively. Early mortality was significantly higher in case of urgent split liver transplantation (3/5 patients vs. 2/32 elective patients - p 0.001).At present 25 patients are alive, with a mean Karnofsky score of 90%.
Three and 12 months graft survival rates were 91.7% and 87.1% respectively. Three and one grafts were lost due to primary and early graft non-function.
In-situ split grafts had shorter mean warm, cold, total ischemia and operating times as well as less need for blood transfusion ; all these differences were however not statistically significant.
Surgical complications occurred in 19 (51%) patients. All but one complications occurred early (< 3 months). There were sixteen biliary complications in 13 (35.1%) patients: 9 anastomotic stenoses, 3 anastomotic and 4 transection margin leakages. Six vascular complications occurred in 6 (15.2%) patients : three arte- rial and 3 portal vein thromboses. Seven (18.9%) patients had a postoperative bleeding.
Conclusions : Graft and patient survival rates of split liver transplantation can be compared to those of classic liver trans- plantation. However the care of these patients is demanding due to the high number of technical complications. Results of split liver transplantation must be further improved in order to foster it's more widespread use necessary to overcome the actual shortage of liver allografts. (Acta gastroenterol. belg., 2005, 68, 369-375).
Long-term Outcome of Urea Cycle Disorders
Evaluation of long-term outcome of patients with urea cycle diseases (UCD) is needed for medical decisions and counselling. Own data comparing outcome of UCD patients with the old treat- ment limited to protein restriction (i.e. close to the natural history) with that of patients on the modern conservative treatment have shown that gains in survival occur at the cost of more mentally retarded surviving patients. We discuss the possible bias in long- term outcome studies of those rare inheritable disorders where non-predictable environmental factors leading to catabolic crises have a crucial impact on prognosis. A combination of peak or ini- tial ammonia value combined with the duration of coma is dis- cussed as a criterion for prognosis of handicap. The neglect of dietary compensation of branched chain amino acid deficiency worsened by phenylbutyrate treatment in some published proto- cols could well be an additional cause of the non satisfactory long- term results of conservative treatment which - in our view - main- ly aim at bridging optimally the period of late neonatal presenta- tion until liver transplantation in patients with CPS and OTC defi- ciency (except for mild forms).