Quality of Life After Liver Transplantation
Twenty-three studies were included in this systematic review (Fig. 1). Heterogeneous data precluded meta-analysis. Key factors were statistical (no preoperative data, data not expressed as mean ± standard deviation), methodological (different QOL scoring systems) and clinical heterogeneity (diverse range of comparison groups). Full details and results of the reviewed articles are provided in Table 1 and Table 2.
The strength of evidence was analysed systematically in this review (Table 1). We aimed to minimize reporting bias with a comprehensive search of the literature for all studies that meet our eligibility criteria. There was a diverse range of aetiologies for end-stage CLD that included primary and other malignancies, alcoholic liver disease, infectious hepatitis, autoimmune diseases of the biliary tract and genetic diseases. This is a potential source of bias as different aetiologies may have impact QOL differently. The sample size ranged between 13 and 1479 and the mean or median age at time of transplantation was between 28 and 59.
Follow-up was conducted over a period of 5 months to 20 years. The majority of studies analysed in this review had follow-up duration of 5–10 years. Follow-up consistency was variable. According to previous guidelines, a response rate of >85% (loss to follow-up <15%) is considered ideal for treatment received analyses. Ten studies did not achieve this and five studies did not report their response rates. Patients who failed to respond may be more likely to be unwilling or unable to because of illness or being deceased, which may skew the data positively.
There were eight prospective studies and 15 retrospective studies. Only three studies included patients' own preoperative QOL data. The lack of patients' respective preoperative QOL data is attributed to a retrospective study design and may preclude information on direction and magnitude of change in QOL. However, indirect comparison of QOL data to preoperative cohorts provides this information in the absence of direct data.
Disease-specific QOL tools were used in nine studies. SF-36 was the most commonly utilized generic QOL instrument. Two studies tailored previously validated QOL assessment tools to patients undergoing liver transplantation.
The studies included in this review reported survival rates of 51–92% at 10 years after liver transplantation and 37–56% at 18–20 years.
Complications specific to liver transplantation were assessed in five studies. Disease recurrence was 17% in one study over a mean follow-up of 109 months. Sainz-Barriga et al. reported recurrence of chronic hepatitis C infection in up to 90% of patients whose 5-year survival rate was 10–28%. Early rejection (22–52%) was more common than late rejection (9–4%). Biliary complications such as biliary leak, common hepatic artery thrombosis and anastomotic biliary stenosis occurred in up to 32% of patients. Reoperations occurred in 15–35% in these studies. New comorbidities after surgery such as osteoporosis (48%), skin cancer (33%), non-skin cancers (38%) hypertension (64%) and diabetes (20%) are common.
Complete results of qualitative analysis are provided in Table 2 with data at latest follow-up tabulated.
Compared to Preoperative Group. All included studies found that liver transplantation improved overall QOL when compared with preoperative or equivalent waitlisted preoperative patients. QOL improved after liver transplantation compared to patients' own preoperative status in all domains. Physical function is a strong benefactor of surgery. Patients report improvement in feelings of loneliness, anxiety and hopelessness, allowing higher quality of social interactions. Sainz-Barriga et al. reported improvements in all domains of QOL except the psychological domain. The Leiden and Padua Questionnaire (LEIPAD) and the Brief Symptom Inventory scores improved most dramatically in the first 2 years after liver transplantation and remained better than the waitlisted group after 8 years.
Overall QOL remained satisfactory up to 20 years after surgery particularly in social interaction and emotional and psychosocial function.
Compared to General Population. Seven studies compared SF-36 scores with age-matched controls. Data are conflicted. Four studies found QOL is relatively similar to the general population except for physical functioning. In one study, liver transplantation patients scored slightly higher QOL in all domains including mental, social and functional health. However, physical functioning had no change. Twenty-year survivors had worse, but comparable QOL compared with the general population. The greatest deficit was in physical functioning. However, mental composite scores persisted higher than both preoperative status and general population. In contrast, two studies reported cognitive dysfunction and poor overall QOL.
Compared to Recipients of Other Organ Transplants. Four studies compared QOL with recipients of kidney, heart and/or lung transplants. TxEQ-D and SF-36 scores in all subcategories did not significantly differ between heart, kidney, lung and liver transplants. Psychological health, perceived social and role function were similar to the general population and between organs. Liver transplantation scored highest in general health perception and personality scale. Overall QOL was also better in liver transplantation than kidney transplantation. QOL of patients following liver, kidney and heart transplantations was worse than the general population, especially in physical health and personal function. Poorer QOL is associated with high-intensity immunosuppressant regimens.
Functional Status. The majority of patients undergoing liver transplantation are of working age (28–59 years) at the time of surgery. Up to half were employed at the time of follow-up. The overall rate of employment declines after 5 years with 67% retired by 8 years. Across the studies assessing employment, patients returning to work post-operatively reported higher QOL scores. Employment status differed according to aetiology of liver disease. Rates of resumption of work were highest in primary sclerosing cholangitis, and lowest in acute liver failure, primary biliary cirrhosis and alcoholic liver disease.
Ho et al. assessed sexual function in liver transplantation patients. Preoperative sexual dysfunction was present in 24% of respondents and persisted in 15% after surgery. The incidence of sexual problems in both men and women increased by about 25% after transplantation. New sexual problems were reported in 32% of the patients. Incidence of sexual problems in men and women increased from 23.8% and 24.1% prior to transplantation to 51.1% and 40.3% after transplantation. Thirty-six per cent attributed this to immunosuppressive medications. However, Duffy et al. reported improved overall sexual function after transplantation compared to CLD patients.
Physical activity levels were acceptable and contribute to better QOL. Greater involvement in social and physical activities is attributed to amelioration of physical symptoms, fatigue and worry related to CLD. Active patients achieved better scores in domains of physical functioning, bodily pain, general health, social functioning, role limitations caused by emotional problems, and physical and mental component summary scores. The physical component summary score of active individuals achieved similar levels as the general population. Physical activity after surgery is also associated with health benefits in addition to QOL such as decreased surgical complications and new onset comorbidities after surgery.
Results
Study Selection
Twenty-three studies were included in this systematic review (Fig. 1). Heterogeneous data precluded meta-analysis. Key factors were statistical (no preoperative data, data not expressed as mean ± standard deviation), methodological (different QOL scoring systems) and clinical heterogeneity (diverse range of comparison groups). Full details and results of the reviewed articles are provided in Table 1 and Table 2.
Study Characteristics and Risk of Bias Within Studies
The strength of evidence was analysed systematically in this review (Table 1). We aimed to minimize reporting bias with a comprehensive search of the literature for all studies that meet our eligibility criteria. There was a diverse range of aetiologies for end-stage CLD that included primary and other malignancies, alcoholic liver disease, infectious hepatitis, autoimmune diseases of the biliary tract and genetic diseases. This is a potential source of bias as different aetiologies may have impact QOL differently. The sample size ranged between 13 and 1479 and the mean or median age at time of transplantation was between 28 and 59.
Follow-up was conducted over a period of 5 months to 20 years. The majority of studies analysed in this review had follow-up duration of 5–10 years. Follow-up consistency was variable. According to previous guidelines, a response rate of >85% (loss to follow-up <15%) is considered ideal for treatment received analyses. Ten studies did not achieve this and five studies did not report their response rates. Patients who failed to respond may be more likely to be unwilling or unable to because of illness or being deceased, which may skew the data positively.
There were eight prospective studies and 15 retrospective studies. Only three studies included patients' own preoperative QOL data. The lack of patients' respective preoperative QOL data is attributed to a retrospective study design and may preclude information on direction and magnitude of change in QOL. However, indirect comparison of QOL data to preoperative cohorts provides this information in the absence of direct data.
Disease-specific QOL tools were used in nine studies. SF-36 was the most commonly utilized generic QOL instrument. Two studies tailored previously validated QOL assessment tools to patients undergoing liver transplantation.
Mortality and Morbidity in Included Studies
The studies included in this review reported survival rates of 51–92% at 10 years after liver transplantation and 37–56% at 18–20 years.
Complications specific to liver transplantation were assessed in five studies. Disease recurrence was 17% in one study over a mean follow-up of 109 months. Sainz-Barriga et al. reported recurrence of chronic hepatitis C infection in up to 90% of patients whose 5-year survival rate was 10–28%. Early rejection (22–52%) was more common than late rejection (9–4%). Biliary complications such as biliary leak, common hepatic artery thrombosis and anastomotic biliary stenosis occurred in up to 32% of patients. Reoperations occurred in 15–35% in these studies. New comorbidities after surgery such as osteoporosis (48%), skin cancer (33%), non-skin cancers (38%) hypertension (64%) and diabetes (20%) are common.
Quality of Life Outcomes
Complete results of qualitative analysis are provided in Table 2 with data at latest follow-up tabulated.
Compared to Preoperative Group. All included studies found that liver transplantation improved overall QOL when compared with preoperative or equivalent waitlisted preoperative patients. QOL improved after liver transplantation compared to patients' own preoperative status in all domains. Physical function is a strong benefactor of surgery. Patients report improvement in feelings of loneliness, anxiety and hopelessness, allowing higher quality of social interactions. Sainz-Barriga et al. reported improvements in all domains of QOL except the psychological domain. The Leiden and Padua Questionnaire (LEIPAD) and the Brief Symptom Inventory scores improved most dramatically in the first 2 years after liver transplantation and remained better than the waitlisted group after 8 years.
Overall QOL remained satisfactory up to 20 years after surgery particularly in social interaction and emotional and psychosocial function.
Compared to General Population. Seven studies compared SF-36 scores with age-matched controls. Data are conflicted. Four studies found QOL is relatively similar to the general population except for physical functioning. In one study, liver transplantation patients scored slightly higher QOL in all domains including mental, social and functional health. However, physical functioning had no change. Twenty-year survivors had worse, but comparable QOL compared with the general population. The greatest deficit was in physical functioning. However, mental composite scores persisted higher than both preoperative status and general population. In contrast, two studies reported cognitive dysfunction and poor overall QOL.
Compared to Recipients of Other Organ Transplants. Four studies compared QOL with recipients of kidney, heart and/or lung transplants. TxEQ-D and SF-36 scores in all subcategories did not significantly differ between heart, kidney, lung and liver transplants. Psychological health, perceived social and role function were similar to the general population and between organs. Liver transplantation scored highest in general health perception and personality scale. Overall QOL was also better in liver transplantation than kidney transplantation. QOL of patients following liver, kidney and heart transplantations was worse than the general population, especially in physical health and personal function. Poorer QOL is associated with high-intensity immunosuppressant regimens.
Functional Status. The majority of patients undergoing liver transplantation are of working age (28–59 years) at the time of surgery. Up to half were employed at the time of follow-up. The overall rate of employment declines after 5 years with 67% retired by 8 years. Across the studies assessing employment, patients returning to work post-operatively reported higher QOL scores. Employment status differed according to aetiology of liver disease. Rates of resumption of work were highest in primary sclerosing cholangitis, and lowest in acute liver failure, primary biliary cirrhosis and alcoholic liver disease.
Ho et al. assessed sexual function in liver transplantation patients. Preoperative sexual dysfunction was present in 24% of respondents and persisted in 15% after surgery. The incidence of sexual problems in both men and women increased by about 25% after transplantation. New sexual problems were reported in 32% of the patients. Incidence of sexual problems in men and women increased from 23.8% and 24.1% prior to transplantation to 51.1% and 40.3% after transplantation. Thirty-six per cent attributed this to immunosuppressive medications. However, Duffy et al. reported improved overall sexual function after transplantation compared to CLD patients.
Physical activity levels were acceptable and contribute to better QOL. Greater involvement in social and physical activities is attributed to amelioration of physical symptoms, fatigue and worry related to CLD. Active patients achieved better scores in domains of physical functioning, bodily pain, general health, social functioning, role limitations caused by emotional problems, and physical and mental component summary scores. The physical component summary score of active individuals achieved similar levels as the general population. Physical activity after surgery is also associated with health benefits in addition to QOL such as decreased surgical complications and new onset comorbidities after surgery.
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