To our knowledge, this study is the first attempt to evaluate the performance of Kazakhstan's national LTx service from its inception in 2012 to the present in 2023. Such evaluation is essential to improve the national LTx program and better serve the needs of the population. The overall pmp rate for LTx ranged from 0.35 (2012) to 3.77 (2016), with LTx from living donors outperforming LTx from deceased donors many times. Throughout the analyzed period, the number of liver transplant centers varied between 1 and 7 for a population of about 20 million people, with pmp rates ranging from 0.06 to 0.40. A total of 474 patients underwent LTx and 364 patients were on the waiting list but did not receive a transplant. Of these, 181 had died and 183 were alive by the end of 2023, with no significant difference between the two groups. The cumulative 30-day survival rate for the waiting list was 87.0%, and the 1-year survival rate was 68.0%. The prevalence of certain types of viral hepatitis and cirrhosis has steadily increased from 2015 to 2023, and this trend is projected to continue through 2030. Without targeted interventions, pmp rates in LTx and liver transplant centers are expected to remain stable, leading to a backlog of unoperated patients waiting for transplant. These findings warrant further detailed investigation.
According to GODT data, in 2022, Kazakhstan ranks 11th in the list of countries based on pmp rates of LTx from living donors, down from 8th place in 2021. However, the overall pmp rate of LTx in Kazakhstan is relatively low, with Kazakhstan ranked 48th out of 91 countries in 2021 and 51st in 2022. Nevertheless, Kazakhstan stands out as a leader in LTx activity in Central Asia, outperforming other countries in the region in terms of pmp rates. Compared to other former Soviet countries, Kazakhstan ranked 5th in 2022 and 2021, behind Lithuania, Belarus, Estonia and Georgia. In general, the pattern of LTx activity in Kazakhstan mirrors that seen in the southeastern region, which is characterized by a predominance of LTx from living donors and a relatively low overall pmp rate.Ten.
Regarding transplant centers, Kazakhstan's PMP rate was lower than other regions of the world. For example, in 2022, the PMP of liver transplant centers in the Americas region was 2.4, Europe was 3.0, the Southeast region was 6.7, the Western Pacific region was 7.7, and the Eastern Mediterranean region had the highest PMP rate of liver transplant centers at 13.2.TenKazakhstan has as many liver transplant centres as the UK, which has a population of around 64 million, has seven.16Kazakhstan has a small number of liver transplant centers, with most performing fewer than 10 liver transplants per year. The only high-volume center in the country, the Syzganov National Scientific and Surgical Center, performs up to 32 liver transplants per year.
Currently, LTx services in the country are provided free of charge to residents and are funded by the Health Insurance Fund, which covers the cost of surgery for both recipients and donors, although ancillary costs such as pre-op tests, examinations, and post-op rehabilitation are often self-funded.17There are no budgetary constraints on the number of LTx procedures performed in the country. Nevertheless, the relatively low LTx rate is likely due to the opt-in approach adopted by Kazakhstan.18This approach requires consent for posthumous organ donation, usually obtained from the deceased's next of kin in the absence of a will.19In general, opt-in systems tend to result in fewer organ transplants than opt-out systems, where all deceased people are automatically considered potential donors. Experience in the European region has shown that countries with opt-out systems tend to have higher LTx rates.20Notably, Kazakhstan adopted an opt-out system and saw an increase in organ transplants between 2015 and 2017. However, this changed in 2017 and 2018 when a transplant surgeon was accused of mishandling organ transplants. Although he was eventually exonerated,twenty oneHowever, the impact of this incident was long-lasting, with PMP rates still not reaching 2015-2017 levels six years later.
The Transplant Coordination Center is a non-profit organization that serves as a national intermediary between 40 donor hospitals and 4 transplant centers. The center consolidates information on patients eligible for LTx into a unified national waiting list. Notification criteria from donor hospitals to the Transplant Coordination Center include potential donors who meet the criteria of brain death. Currently, donation after circulatory death is not performed. During the study period, there were no cross-border donor or recipient exchanges with other countries in the region, and all liver transplants were performed exclusively for Kazakhstan nationals. Indication for liver transplantation was determined by a Child-Turcotte-Pugh score of 7 or higher (classes B and C).6The Model for End-Stage Liver Disease (MELD) is not currently in use. Survival analysis revealed a striking proportion of patients facing death soon after waiting list entry, showing a 1-month cumulative mortality rate of 13%, highlighting the potential benefit of including these patients on the waiting list earlier.
Indications for LTx have changed over the past decade. End-stage cirrhosis remains the primary indication.twenty twoCompliant with Kazakhstan's LTx national standards14However, the global etiology of cirrhosis is shifting away from viral hepatitis due to the availability of effective antiviral drugs and lifestyle and dietary changes. In Kazakhstan, the burden of viral hepatitis is high and continues to increase, as can be seen from our findings and previous scientific data.twenty threeDirect-acting anti-hepatitis C drugs are not widely used in Kazakhstan, and although the anti-hepatitis B vaccine was included in the national immunization schedule in 1998, the prevalence of anti-HB core antibodies has been reported at 17.2%, higher than in many other countries.twenty fourProjections of viral hepatitis and cirrhosis through 2030 suggest that the prevalence of these diseases is likely to increase, leading to an increased demand for LTx. However, due to national efforts towards prevention through well-established vaccination programs, it must be recognized that the increasing trend in viral hepatitis B may be related to improved efficiency of reporting rather than an absolute increase.
Indications for liver transplantation in adult patients are usually preventable, such as alcohol use, viral hepatitis, and fatty liver disease, whereas indications in pediatric patients often arise from conditions such as biliary atresia, inborn errors of metabolism, and tumors.twenty fiveThe Pediatric End-Stage Liver Disease score (PELD) is a numerical scoring system utilized to prioritize pediatric patients awaiting LTx. It is designed to assess the severity of liver disease and risk of death in children under 12 years of age. The PELD score considers various clinical parameters and assigns a score ranging from 6 to 40. The higher the score, the greater the severity of liver disease and the higher the risk of death. The PELD scoring system ensures that donor organs are allocated to patients with the greatest medical need.26.
Efforts to address the unique challenges and requirements of pediatric LTx include the establishment of specialized pediatric LTx centers. These centers provide expertise in the management of pediatric liver disease, including surgery, perioperative care, and long-term follow-up. The implementation of a national policy dedicated to pediatric LTx could further improve survival rates for children with end-stage liver disease.27Although no such provision is currently in place in Kazakhstan, its implementation could herald improved pediatric survival. Despite advances in pediatric LTx globally, significant challenges remain as many cases of pediatric liver failure are complex and transplantation is only one aspect of the treatment strategy. Therefore, it is essential to continue research and develop comprehensive approaches to address the multifaceted needs of pediatric patients with end-stage liver disease.28.
In Kazakhstan, public health efforts to intensify LTx activity are essential to meet the increasing demand for LTx procedures. In efforts to expand the pool of available grafts, challenges are illustrated by the large number of marginal donors. These cadaveric donors are at high risk of primary failure and early graft failure, and have suboptimal long-term outcomes when compared with grafts from donors with less challenging criteria.29As a result, an active and widespread campaign aimed at raising awareness among the general public about organ donation with the help of primary health care, mass media, community-based interventions and research institutes has become imperative.30,31,32,33.
This study had several limitations. The main limitation is that the available data on the national waiting list of patients waiting for LTx are limited, with many specific details related to missing underlying diagnoses. This limitation precludes the calculation of cause-specific survival rates and limits the analysis of associated risk factors. Another limitation is that the predictive modeling used the prevalence of specific types of viral hepatitis, liver fibrosis, and cirrhosis, but data for end-stage liver disease were not available and the study relied only on ICD-10 codes, limiting its predictive power. Moreover, the predicted rates of both liver disease prevalence and LTx rates should be interpreted with caution, as they indicate the need for public health measures to address the current situation. Nevertheless, this study has several strengths, most notably being the first national study to analyze the output and outcomes of LTx services.
