Effect of Orthotopic Liver Transplantation on the Health-Related Quality of Life in Indian Patients with End-Stage Liver Disease: A Prospective Study

Health-related quality of life (HRQOL) is an important measure of the effects of end stage liver disease in affected patients that helps to improve well-being after Liver transplantation (LT). One study has been performed to access HRQoL pre and post liver transplant (LT) patients in India. Our study was aimed to determine HRQoL in pre and post orthotopic liver transplant (OLT) with correlation between severity of liver disease by Model for End-Stage Liver Disease (MELD)/Child-Turcotte-Pugh (CTP) score and Diabetes Mellitus (DM) status with HRQoL post OLT. liver forming the second and third largest groups respectively. was post OLT also correlation of MELD/CTP scores and diabetes status with post-OLT HRQoL was determined. Patients were followed up for a period of 3 months after OLT.


Introduction
End-stage liver disease is a progressive illness with liver transplantation (LT) as an established form of treatment 1 . In India with a population of 1.37 billion till March 2019, the end-stage liver disease is becoming increasingly prevalent with an estimated annual requirement of LT between 30,000 and 32,000.
Currently, only about 2200 to 2500 liver transplants operations are being performed due to limited cadaveric donor pool 2, 3 and the approved number of government recognized centers 4 .
Liver transplantation is the gold standard therapeutic option for end-stage liver disease 5 . In the last few decades, there have been progressive improvements in graft and patient survival 6 . The1, 5-and 10-years survival has been reported to be 92%, 83%, and 79%, respectively 7 . Etiological categorization of end-stage liver disease revealed the hepatitis C virus (HCV), hepatitis B virus (HBV), ethanol-related, and cryptogenic cirrhosis as a major cause of liver damage 8 . Patients with the end-stage Liver disease have a negative impact on daily health-related quality of life (HRQoL). As life expectancy after liver transplantation continuously improving, there has been a transit from the medical management of LT recipients to a more long-term approach in form of HRQoL, which includes not only the physical well-being of recipients but also their social and emotional well-being.
The quality of life of recipients evaluated by several studies and has determined important elements such as medical complications, physical function, social function, fatigue, employment status, emotional function, and sexual dysfunction 9 . These studies have shown that the quality of life improves after LT; this is demonstrated by improvements in a recipient's functional capacity, perception of health condition, and self-esteem and these parameters continue to revamp over time. Short form-36(SF-36) is a validated questionnaire derived from a larger set of questions and provides a composite scale of mental and physical health for patients. Studies published outside India reported positive outcomes in HRQoL after LT 10,11,12 . In Indian scenario two studies have been reported with one determining HRQoL using SF-36 in liver cirrhosis patients compared with the same age and gender healthy controls, the severity of liver disease in this study was assessed by MELD and CTP scoring 13 while in another study Bidare et al 14 assed HRQoL using SF-36 in pre and post LT; hence this study will provide more insight on HRQoL in pre and post LT Indian patient's, Also it will give information on the correlation between the severity of liver disease (MELD and CTP) and Diabetes mellitus (DM).

Material And Methods
The study was designed as a prospective, observational, and single-center study. Sixty end-stage liver disease patients evaluated for LT at Sir Ganga Ram Hospital, New Delhi between June 2013 to March 2015 in the department of Surgical Gastroenterology and Liver Transplantation were enrolled in the study. This study is approved by the Institutional ethics committee board (EC/08/13/586). Informed and written consent for participation was obtained from all the recipients and they all completed the validated SF-36 questionnaire by interview or E-mail pre-LT as well as Post-LT follow-up at 3 months. The study was performed under a license approval certi cate (License Number-QM029912, Optuminsight Life Sciences, Inc) for the use of the SF-36 software. The results from questionnaires completed by interview versus mail were equivalent. In this study chronic end-stage liver disease patients were included like HCV-related cirrhosis, alcoholic liver cirrhosis, HBV-related cirrhosis, Autoimmune, Budd Chiari Syndrome, and nonalcoholic fatty liver (NASH). The other inclusion criteria were age ≥18 years, a fully-conscious, ambulatory, liver transplant recipient. Patients with acute liver failure, multiple-organ transplant listed, and patients not willing to participate or complete the SF-36 questionnaire were excluded.

Post-transplant Follow-up protocol
Our institute developed its own post -LT follow-up protocol model to assess the physical and psychosocial recovery of our recipients. At the time of discharge, recipients and their family members were educated about healthy lifestyle and general daily life precautions. It was also suggested that patients should visit transplant physicians or surgeons monthly in the rst 6 months, every 3 monthly in the second 6 months, and 6 monthly beyond 1 year. Recipients were instructed to follow up with our transplant physicians in the out-patient clinic or by mail or telephone if they had any health-related problems.
Regularly, our institute staff also doing telephonic communication with the recipient to know general health. Patients were further evaluated with clinical and laboratory investigation stools, and intervention or even readmission, in case any abnormalities were identi ed. Furthermore, an annual meeting was held to update our recipients with information related to medication and daily care, and maintaining optimum HRQoL was emboldened at the annual meeting.

SF-36-Tool to evaluate HRQoL
The SF-36 questionnaire was used to evaluate HRQoL consisting 36 questions (items) measuring physical and mental health status with eight health parameters: physical functioning (PF), role limitations due to physical problems: role physical (PR), body pain (BP), general health perceptions (GH), vitality: energy/fatigue (VT), social function (SF), role limitations due to emotional problems: role emotional (ER), and general mental health: psychological distress/wellbeing (MH). The SF-36 questionnaire was given to the recipient's pre and post-liver transplantation by interview or mail-in language he/she understands (Hindi and English version). Responses to each of the SF-36 items were scored and summed according to a standardized scoring protocol and expressed as a score on a 0-100 scale for each of the eight health concepts. Higher scores represent better self-perceived health. The maximum of 100 on these bipolar scales, therefore, indicated not just the absence of disability, but the presence of a positive state of health. Two-component summary measures have been calculated from eight health parameters: The Physical Component Score (PCS) and Mental Component Score (MCS). The summary scores were aggregated measures of the physical health and mental health dimensions underlying the SF-36 questionnaire. The severity of liver disease was assessed before transplant with MELD and CTP scores, with the diabetes status of the patients. The correlation between the severity of disease (MELD, CTP) and DM status with HRQoL at 3 months post-transplant was also evaluated.

Statistical analysis
Statistical data were analyzed by using Statistical Package for the Social Sciences (SPSS), version 17. Data values were calculated using software provided by the SF36 health questionnaire and reported as mean ± SD. The Categorical numbers were expressed as percentages and frequencies. Nominal categorical variables between the groups were compared using a nonparametric sign test, while the Paired t-test was used to compare the normally distributed continuous variables pre-operative and postoperative 3 months. Spearman correlation analysis was used to analyze the relationships between HRQoL and pre-transplantation severity of liver disease and DM status, a p-value of <0.05 was considered statistically signi cant.

Recipient Characteristics
The demographic characteristics of the study population are listed in Table 1. Most recipient's average age was 45 years at the time of transplantation and male (83.3%) to female (16.7%) ratio was 5:1. Classi cation by primary liver disease at the time of referral for transplantation showed that the largest group had HCV related cirrhosis with alcoholic and cryptogenic liver disease forming the second and third largest groups respectively. Among the participants, 13.3% had Hepatocellular carcinoma (HCC), 26.7% had Spontaneous bacterial peritonitis (SBP), 36.7% experienced Hepato-renal syndrome (HRS) and18.3% had Diabetes mellitus (DM), while 16.7% reported that they experienced early postoperative sepsis. All recipients underwent living donor LT, all of whom were rst or second-degree relatives of their donors. The HRQoL scores of pre and post-transplant are mentioned in Table 2 and Fig. 1 There was a great   Table 3.There was a negative correlation between overall SF-36 scores and MELD/CTP scores.
In MELD negative correlation was found in VT (r= -0.32, p < 0.05) and MCS (r= -30, p < 0.05), while in CTP negative correlation was observed in PF (r=-0.30, p < 0.05), which were found to be signi cant. No signi cant correlation was observed between the presence of diabetes mellitus and HRQoL after OLT. Correlation coe cient between SF-36 and MELD / CTP and DM, Data analyzed using Spearman correlation test (*p < 0.05).

Discussion
The current study analyzed pre and post-liver transplant recipients HRQoL by using the SF-36 questionnaire, the pre-transplant patients were found to have low HRQoL scores indicating the altered quality of life. End-stage liver disease has a negative effect on all aspects of a patient's well-being and

Limitations Of The Study
Our study has a few important limitations. First, relatively few patients were enrolled in the study. Thus, it would be appropriate to extend it to include more number of patients. Second, the study had short term follow up and HRQoL assed once only after the rst 3 months post LT, hence it is very di cult to assess long term HRQoL. Third, in this study pre LT patients were compared with post LT patients, however, in other studies post LT recipients were compared with the healthy general population. Lastly, there are many studies in which employment, income, sexual and reproductive parameters analyzed after transplant, but the present study didn't assed these.
In conclusion, there was a signi cant increase in HRQoL at rst quarter post-LT with no prediction between the severity of disease and diabetes status in Indian patients. However, HRQoL and correlation between severities of liver disease should be evaluated for a longer duration of time on larger Indian liver transplant population