Preventing hepatitis B and hepatocellular carcinoma in South Africa: The case for a birth-dose vaccine.

Hepatitis B is a global public health issue, with some 2 billion people having current or past infection. In Africa, 65 million are chronically infected, an estimated 2.5 million of them in South Africa (SA). Hepatitis B and the associated complications of cirrhosis and hepatocellular carcinoma are entirely vaccine preventable. SA was one of the first ten countries in Africa to introduce universal hepatitis B vaccination in April 1995, but has no birth dose or catch-up programme. Although universal infant vaccination in SA has been successful in increasing population immunity to hepatitis B, improvements in terms of implementing protocols to screen all pregnant mothers for hepatitis B surface antigen (HBsAg) and ensuring full hepatitis B coverage, especially in rural areas, is justified. The World Health Organization has recommended a birth dose of hepatitis B vaccine in addition to the existing hepatitis B vaccine schedule in order to further decrease the risk of perinatal transmission. We recommend that SA implement a birth-dose vaccine into the existing schedule to attenuate the risk of perinatal transmission, prevent breakthrough infections and decrease HBsAg carriage in babies born to HIV-positive mothers.

Challenges for paediatric transplantation in Africa.

Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine. Long-term outcomes have significantly improved and the aim of management is no longer only long-term survival, but also focuses on quality of life especially in children. Transplantation in Africa faces a number of challenges including wide socioeconomic disparity, lack of legislation around brain death and organ donation in many countries, shortage of skilled medical personnel and facilities, infectious disease burden and insecure access to and monitoring of immunosuppression. Whilst there is a need for transplantation, the establishment and sustainability of transplant programmes require careful planning with national government and institutional support. Legislation regarding brain death diagnosis and organ retrieval/donation; appropriate training of the transplant team; and transparent and equitable criteria for organ allocation are important to establish before embarking on a transplant programme. Establishing sustainable, self-sufficient transplant programmes in Africa with equal access to all citizens is an important step towards curtailing transplant tourism and organ trafficking and has a further beneficial effect in raising the level of medical and surgical care in these countries.

Immune tolerance and immunosuppression in solid organ transplantation.

Organ transplantation is the treatment of choice for patients with end-stage organ failure. Most of them will require lifelong immunosuppression to prevent both acute and chronic rejection. T-cell recognition of the allograft major histocompatibility complex antigens is the central event initiating cellular rejection of the allograft, and subsequent full T-cell activation requires three signals.Immunosuppressive regimens currently used in clinical practice are nonspecific and target T-cell activation, clonal expansion or differentiation into effector T cells. While these therapeutic regimens have advanced considerably and one-year graft survival figures for most solid organ transplants (SOTs) are >90%, the long-term graft survival remains fair owing to graft loss from chronic rejection. The 'holy grail' of SOT is therefore the development of a permanent specific immune tolerance against donor allogeneic antigens without the long-term use of immunosuppression.

South African guideline for the management of chronic hepatitis B: 2013.

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.

Pregnancy following liver transplantation during childhood and adolescence.

More than 80% of pediatric transplant recipients will survive to reach adulthood, and many will consider having children. We report on outcomes and management of five pregnancies in four women undergoing orthotopic liver transplantation during childhood or adolescence and followed up at our Transplant Center. A retrospective clinical folder audit was performed. Mean age at transplantation was 13.3 ± 3.4 yr (range, 10-18 yr). Mean interval between transplantation and pregnancy was 15.4 ± 4.9 yr (range, 10-22 yr). Mean maternal age at conception was 28 ± 3.5 yr (range, 23-32 yr). Mean gestational age was 36.6 ± 1.7 wk. Mean birth weight was 2672 ± 249 g. Immunosuppression was cyclosporin based in three women and tacrolimus based in one woman. Pregnancy complications necessitating the induction of labor included fetal distress and rising maternal liver enzymes in two women, cholestasis of pregnancy and impaired renal graft function in one woman, fetal distress and preeclampsia in one woman. Modes of delivery were normal vaginal delivery in three women and cesarean section in one woman. No maternal or fetal deaths and no congenital malformations occurred. No episodes of rejection occurred during pregnancy. Two women experienced acute cellular rejection requiring an increase in baseline immunosuppression in the first year, following delivery. No graft losses occurred during a mean follow-up of 44 ± 17.9 months post-delivery. With careful management, pregnancy post-liver transplantation can have a successful outcome.

Overview of a paediatric renal transplant programme.

INTRODUCTION: Renal transplantation is the therapy of choice for children with end-stage renal failure. There are many challenges associated with a paediatric programme in a developing country where organs are limited. METHODS: A retrospective review was undertaken of 149 paediatric renal transplants performed between 1968 and 2006 with specific emphasis on transplants performed in the last 10 years. Survival of patients and grafts was analysed and specific problems related to drugs and infections were reviewed. RESULTS: On review of the total programme, 60% of the transplants have been performed in the last 10 years, with satisfactory overall patient and graft survival for the first 8 years post transplant. At this point, transfer to adult units with non-compliance becomes a significant problem. Rejection is less of a problem than previously but infection is now a bigger issue--specifically tuberculosis (TB), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections with related complications. A wide variety of drugs are available for tailoring immunosuppression to minimise side-effects. CONCLUSION: It is possible to have a successful paediatric transplant programme in a developing country. However, to improve long-term outcomes certain issues need to be addressed, including reduction of nephrotoxic drugs and cardiovascular risk factors and providing successful adolescent to adult unit transition.

Liver transplantation at Red Cross War Memorial Children's Hospital.

UNLABELLED: The liver transplant programme for infants and children at Red Cross War Memorial Children's Hospital is the only established paediatric service in sub-Saharan Africa. Referrals for liver transplant assessment come from most provinces within South Africa as well as neighbouring countries. PATIENTS AND METHODS: Since 1987, 81 children (range 6 months-14 years) have had 84 liver transplants with biliary atresia being the most frequent diagnosis. The indications for transplantation include biliary atresia (48), metabolic (7), fulminant hepatic failure (10), redo transplants (3) and other (16). Four combined liver/kidney transplants have been performed. Fifty-three were reduced-size transplants with donor/recipient weight ratios ranging from 2:1 to 11:1 and 32 children weighed less than 10 kg. RESULTS: Sixty patients (74%) survived 3 months-14 years post-transplant. Overall cumulative 1- and 5-year patient survival figures are 79% and 70% respectively. However, with the introduction of prophylactic intravenous ganciclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive donors, the 1-year patient survival is 90% and the projected 5-year paediatric survival is > 80%. Early (< 1 month) post-liver-transplant mortality was low. Causes include primary malfunction (1), inferior vena cava thrombosis (1), bleeding oesophageal ulcer (1), sepsis (1) and cerebral oedema (1). Late morbidity and mortality was mainly due to infections: de novo hepatitis B (5 patients, 2 deaths), Epstein-Barr virus (EBV)- related post-transplantation lymphoproliferative disease (12 patients, 7 deaths) and cytomegalovirus (CMV) disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in 3 patients was complicated by chronic rejection (1) and TB-drug-induced subfulminant liver failure (1). CONCLUSION: Despite limited resources, a successful paediatric programme has been established with good patient and graft survival figures and excellent quality of life. Shortage of donors because of infection with HBV and human immunodeficiency virus (HIV) leads to significant waiting-list mortality and infrequent transplantation.

Liver transplantation for children: Red Cross Children's Hospital experience.

BACKGROUND: The liver transplant program for infants and children at the Red Cross Children's Memorial Hospital is the only established pediatric service in sub-Saharan Africa. Since 1985, 250 infants and children have been assessed and 155 accepted for transplantation. METHODS: Since 1987, 76 children (range 6 months to 14 years) have had 79 liver transplants, with biliary atresia being the most frequent diagnosis. The indications for transplantation include biliary atresia (n = 44), metabolic (n = 7), fulminant hepatic failure (n = 10), redo transplants (n = 3), and other (n = 15). Three combined liver/kidney transplants have been performed. Forty-nine were reduced-size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1, and 29 children weighed < 10 kg. RESULTS: Fifty-six (74%) patients survived 3 months to 12 years posttransplant. Cumulative 1- and 5-year patient survival data are 79% and 70%, respectively. However, with the introduction of prophylactic intravenous gancyclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive donors, the projected 5-year pediatric survival has been >80%. Early (<1 month) post-liver-transplant mortality was low, but included: primary malfunction (n = 1); inferior vena cava thrombosis (n = 1); bleeding esophageal ulcer (n = 1); and sepsis (n = 1). Late morbidity and mortality was mainly due to infections: de novo hepatitis B (5 patients, 2 deaths); Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (12 patients, 7 deaths); and cytomegalovirus disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in three patients was complicated by chronic rejection (n = 1) and TB drug-induced subfulminant liver failure (n = 1). CONCLUSIONS: Despite limited resources, a successful pediatric program has been established with good patient and graft survival figures and excellent quality of life. Shortage of donors due to HBV and human immunodeficiency virus (HIV) leads to significant waiting list mortality and infrequent transplantation.

Nephrotoxic effects of immunosuppressant therapy in pediatric liver transplant recipients.

Drugs used for immunosuppression have been implicated in causing numerous long-term side effects including nephrotoxicity, glucose intolerance, and hyperlipidemia. In this study, we reviewed our pediatric liver transplant recipients in terms of glomerular filtration rate (GFR) as well as fasting glucose and lipid profiles. To date, 79 pediatric liver transplantations have been performed at our center: 24 transplantations of at least 5 months to a maximum of 7.3 years posttransplant are reviewed herein. The mean time posttransplantation was 2.1 years. Nine boys and 15 girls showed a distribution of 19 mixed race, 3 black, and 2 white patients. The mean age at the time of transplantation was 6.6 years (0.8-13.3 years) with 8 cases under the age of 3 years. All recipients started with Cyclosporine Neoral (CSA) as first line, but, at the time of testing, immunosuppression included 5 children on CSA and 19 on Tacrolimus. Radionuclide 51 Cr-EDTA Glomerular Filtration Rates (GFR) showed a range from 21 to 220 mL/min/1.73 m2 (mean 96.1, median 89.8). Seven cases had a GFR less than 75 mL/min/1.73 m2. Twenty-one children were on antihypertensives agents: 15 children on 1 agent and 6 children on 2 agents. On full fasting lipid profiles, the total cholesterol ranged from 2 to 7.9 mmol/L (mean 4.4). Only 1 child is currently on statin therapy. Fasting glucose ranged from 3.2 to 5.9 mmol/L (mean 4.1) No difference was observed in glucose values between CsA and Tacrolimus. Thus, immunosuppressive therapies, such as the calcineurin inhibitors, are known to cause nephrotoxicity, which is of concern in pediatric liver transplant recipients. Almost all our patients currently require antihypertensive therapy. At present, the renal function is adequate in the majority of the group, but this study needs to be extended to other pediatric liver transplant recipients with particular emphasis on those who are more than 5 years posttransplantation.