**4. HRQOL in patients with chronic liver disease is not associated with disease severity as measured by MELD (Model for End-stage Liver Disease) score**

Liver transplant is indicated in selected patients with advanced liver disease in which other therapeutic measures have failed or are not possible, and with no absolute contraindications for this procedure. (Consensus Document of the Spanish Society of Liver Transplant, 2009).

Some type of balance between need and utility has to be considered, meaning that we should be cautious with patients with a very severe clinical prognosis when taking advantage of a scarce resource, a liver graft. In our opinion, ideally, there should be a balance between the subjective perception of health by the patient, friends and close family and the clinical severity of the disease based on medical data when deciding on when to do the transplant.

However, some difficulties have to be taken into account. Clinicians base their decisions on objective measures, such as analysis and image tests for clinical diagnosis and treatment but the moment of transplant also depends on the waiting list and the feasibility of a suitable donor. Ideally, it would be desirable to consider both biological objective measures and more subjective measures, such as HRQOL (Kanwal, 2004).

HRQOL in chronic liver patients has been shown to be impaired in numerous studies. Gutteling et al. 2006, studied the impact of physical and psychosocial determinants on a weighted score of HRQOL in patients with chronic liver disease. They showed that HRQOL was related to disease severity and joint pain. Also depression, decreased appetite and fatigue were strongly related to HRQOL. In hepatitis C patients, fatigue and depression were powerful determinants of HRQOL (Strauss, 2006). Patients with cirrhosis who had a

Effects on the properties of questionnaires of HRQOL related to the mode of administration have been studied (Table 4) (Hays, 2009; Gundy, 2010). Significant differences were detected in measurements –after adjustment- researchers found that, for the Emotional Functioning (EF) scale, patients who had completed the written questionnaire at home had significantly

Ascites None Controlled Poor control Encephalopathy None Grade I-II Grade III-IV Total bilirubin, µmol/L (normal = 17.1 µmol/L) < 34 34 – 50 > 50 Albumin, g/L >3.5 g/dL) 2.5-3.5 g/dL < 2.5 g/dL INR < 1.7 1.7–2.2 >2.2

Table 5. Scoring severity of liver disease MELD (Malinchoc, 2000; Kamath, 2001) and Child-Pugh (Pugh, 1973). MELD score was developed to determine the severity of liver disease based on the patient's serum bilirubin, serum creatinine, and the international normalized ration (INR).It has been proposed to replace the Child-Turcotte-Pugh (CTP) score as a "more

**4. HRQOL in patients with chronic liver disease is not associated with disease severity as measured by MELD (Model for End-stage Liver Disease)** 

Liver transplant is indicated in selected patients with advanced liver disease in which other therapeutic measures have failed or are not possible, and with no absolute contraindications for this procedure. (Consensus Document of the Spanish Society of Liver

Some type of balance between need and utility has to be considered, meaning that we should be cautious with patients with a very severe clinical prognosis when taking advantage of a scarce resource, a liver graft. In our opinion, ideally, there should be a balance between the subjective perception of health by the patient, friends and close family and the clinical severity of the disease based on medical data when deciding on when to do

However, some difficulties have to be taken into account. Clinicians base their decisions on objective measures, such as analysis and image tests for clinical diagnosis and treatment but the moment of transplant also depends on the waiting list and the feasibility of a suitable donor. Ideally, it would be desirable to consider both biological objective measures and

HRQOL in chronic liver patients has been shown to be impaired in numerous studies. Gutteling et al. 2006, studied the impact of physical and psychosocial determinants on a weighted score of HRQOL in patients with chronic liver disease. They showed that HRQOL was related to disease severity and joint pain. Also depression, decreased appetite and fatigue were strongly related to HRQOL. In hepatitis C patients, fatigue and depression were powerful determinants of HRQOL (Strauss, 2006). Patients with cirrhosis who had a

1 point each 2 points each 3 points each

lower levels of (EF) compared to those interviewed over the telephone.

**Child-Turcotte-Pugh (CTP), Prognosis of liver disease.**  (CTP A = 5-6 p, CTP B = 7-9 p, CTP C = 10-15 p)

objective" measure of chronic liver disease severity

more subjective measures, such as HRQOL (Kanwal, 2004).

**score** 

Transplant, 2009).

the transplant.

higher Child-Pugh score (measuring disease severity) presented symptoms such as muscle cramps, pruritus, and fatigue (Marchesini, 2001), significant factors relating to QOL. Comorbid conditions and the duration of disease have not shown in the majority of studies a significant relationship with QOL in these patients. However, the relationship between psychological distress, symptoms and QOL is less known.

Some authors, studying the association between HRQOL and survival in patients with cirrhosis, showed that the relation between HRQOL and survival was MELD (Model of En-Stage Liver Disease) independent (Kanwal, 2004; Saab, 2005). Kanwal et al., found that higher baseline HRQOL predicted lower mortality (Kanwal, 2009). Specifically, for each 1 point increase in HRQOL, there was a 4% decrease in mortality. Both social relations and support have proved to be favourable predictors.

Considering that HRQOL has been recognized as an important outcome in chronic liver diseases, and clearly determined by disease severity, some changes might be applied in the clinical practice. For example, it could be useful to develop a form of intervention aimed at improving adaptation to the more frequently identified symptoms and to implement the use of a comprehensive assessment of QOL in the evolution of chronic liver disease patients with the aim of better clinical management.

However, in everyday practice, the instruments evaluating QOL in liver disease are rarely used due to lack of time and resource constraints (Sanders, 1998; Gutteling, 2007). Some doctors, having different priorities, are hesitant to implement this issue. MELD is being used to prioritize patients for liver transplantation, with the purpose of limiting mortality in patients on the waiting list (Wiesner, 2003). There are paucity of data evaluating associations between MELD score and patient-centered outcomes (HRQOL). Kanwal et al. in 2004 publication "Does Model for End-stage Liver Disease (MELD) predict HRQOL in patients with advanced chronic liver disease?" explore these associations. Their research on correlations between MELD/CTP and patient-centered outcomes evidenced that in persons with advanced chronic liver disease, MELD score predicts patient self-rated severity of liver disease symptoms, but fails to predict disability days and the more global outcome of HRQOL (Kanwal, 2004).

CTP score may be a better proxy measure than MELD, due to being based on clinical data and is more patient centered disease in persons with decompensated chronic liver disease (Saab, 2005). Both hepatic encephalopathy and ascites, which can affect quality of life, are not part of the MELD score. Furthermore, the MELD score has not been correlated with the severity of ascites and hepatic encephalopathy. Thus, liver disease severity assessed by the MELD score may no longer correlate with quality of life. (Saab, 2005) (Table 5).

MELD score allows prioritizing patients on the waiting list, putting the "sickest first" (Schaffer, 2003). However, we have to take into account that the MELD score does not always adequately reflect disease severity and prognosis (Frost, 2002). In patients with fulminant hepatic failure, metabolic disease, hepatocellular carcinoma, refractory ascites, hepato pulmonary syndrome etc. MELD does not apply (Schaffer, 2003).

Nowadays, although one of the most used disease severity indices is MELD score, it is not associated with HRQOL. Several patients with decompensated liver disease do not have a high enough MELD score, so we should examine possible causes of the present situation and justify and validate other specific instruments or formulas.
