**8. Clinical relevance of measuring QOL and methodological difficulties**

Liver transplant is a surgery that restores both long-term physiology and well-being in patients with end-stage liver disease. (Tomé, 2008) Factors that have to be considered include the stress of waiting for a liver transplant - with its uncertainty in terms of both timing and outcome - as well as the physical and psychological demands of the procedure in the pre- and post-transplant period (Goetzmann, 2006). Other demands on the long term are linked to general quality of life (QOL) and treatment adherence (Drent, 2009).

It is necessary to differentiate the clinical situation of patients with acute liver disease versus those with chronic liver disease, due to the process of adaptation that usually happens in chronic diseases. Several cross-sectional and longitudinal studies show a statistically significant increase in QOL after transplantation in the majority of patients. Longitudinal studies are preferable to cross sectional studies.

Capture of the HRQOL experiences across disease severity and etiology of the liver disease is challenging because of subtle differences in the disease and the background of the person

The major predictors of poor adherence to medication gives an idea of how we can intervene early in treatment (Bernstein, 2002). There are few studies addressing QOL in relation with anti-HCV treatment after liver transplant (Alsatie, 2007; Neri, 2010). Patient and treatment factors to be aware of are treatment of asymptomatic disease; the presence of psychological problems, particularly depression; a patient's lack of belief in the benefit of treatment; the complexity of the treatment; and adverse events (Schiano, 2006). Other factors that perhaps are harder to quantify are a poor provider-patient relationship, inadequate follow-up or discharge planning, missed appointments, and the cost of medication,

Liver transplant recipients do not, however, achieve the same QOL scores as healthy controls, and the prevalence of psychiatric comorbidities including depression is higher than controls (Dew, 1997). Patients experience more acute anxiety and depression, especially ex-

Despite few physical manifestations of disease at the time of HCV recurrence, patients report an impaired quality of life and functional status compared with other recipients without recurrence (Feurer, 2002). This suggests that patient knowledge of the diagnosis of recurrent HCV alone can negatively impact HRQOL (Hauser, 2004). They perceive themselves as unwell and have significant changes in their mental and physical health despite the absence of disease-related complications. However, only a limited number of studies have investigated the influence of gender, HCV genotype, or HCV antiviral treatment on the HRQOL of liver transplanted patients with HCV recurrence (Feurer, 2002; Saab, 2010).

Complexity of the treatment requires an extra effort by the transplant team, for example before patients leave the hospital after transplant. Adverse events of medication have to be taken into account, possibly in the long-term, due to poorer physical functioning, depression, and greater rates of fatigue some patients can miss some doses. More than 50% of liver transplants recipients survive more than 20 years, achieve important selfachievements, and report quality of life superior to patients with liver disease or other

**8. Clinical relevance of measuring QOL and methodological difficulties** 

linked to general quality of life (QOL) and treatment adherence (Drent, 2009).

Liver transplant is a surgery that restores both long-term physiology and well-being in patients with end-stage liver disease. (Tomé, 2008) Factors that have to be considered include the stress of waiting for a liver transplant - with its uncertainty in terms of both timing and outcome - as well as the physical and psychological demands of the procedure in the pre- and post-transplant period (Goetzmann, 2006). Other demands on the long term are

It is necessary to differentiate the clinical situation of patients with acute liver disease versus those with chronic liver disease, due to the process of adaptation that usually happens in chronic diseases. Several cross-sectional and longitudinal studies show a statistically significant increase in QOL after transplantation in the majority of patients. Longitudinal

Capture of the HRQOL experiences across disease severity and etiology of the liver disease is challenging because of subtle differences in the disease and the background of the person

copayment, or both. (Ghobrial, 2001).

chronic conditions (Ruppert, 2010).

studies are preferable to cross sectional studies.

alcoholics and hepatitis C patients (Paterson, 2000).

(Norman, 2003). Post-transplantation HRQOL scores are not affected in general by the etiology of the original liver cirrhosis, but transplant recipient scores continue to remain significantly lower than those of healthy patient controls. Prospective studies, showing the QOL evolution in the long term follow up, are starting to show differences between the cause of transplant and clinical evolution (Ruppert, 2010). Minimal clinical important difference is a concept defined as the minimal change in HRQOL which is important for the patient, allowing patients to report a minimal yet perceptible change in their health (Norman, 2003). Confirmation of the preliminary results in this group of patients is necessary.

Relapse of substance abuse, especially alcohol consumption, often affects not only QOL, but also adherence to immunosuppressive therapy and thus long-term survival after OLT. As relapse of alcohol addiction occurs in 10 to 30% of OLT recipients, continuous psychological support has an important role in post-transplant care (Pfitzmann, 2007).

The risk of recurrent disease in the graft influences the clinical prognosis. In previous alcoholics, or other addicts, disease recurs in a minority of patients. For example, in alcoholic disease histologically proven disease recurrence is not frequent whereas it is the rule in hepatitis C, and is not common in cases of primary biliary cirrhosis, auto-immune hepatitis, or primary sclerosing cholangitis (Kotlyar, 2006).

In addition to being influenced by the psychological and physical condition of the patient, QOL is also affected by social function and occupational activity. Employment rates in liver transplanted recipients depend on several factors, such as age, education, duration of their disability and country. The number of patients returning to work after transplant ranges from 30% in Germany to about 55% in the United States and Canada (Bravata, 2001; Aberg, 2009).

During the first 6 months after liver transplantation, the majority of physical and mental components of health-related quality of life scores improve, but these increases are not sustained in the long term (De Bona, 2000). At 1 year after liver transplantation, emotional and mental health-related quality of life scores are balanced with a tendency to decrease (Paterson, 2000). In the postoperative years 1 to 5, possible episodes of acute cellular rejection, recurrent disease and patient age over 60 years decrease physical function and overall general QOL scores (Levy, 1995). Beyond 5 years after liver transplantation, osteoporosis, and episodes of chronic rejection may decrease QOL scores through decreases in the physical function and bodily pain domains (Karam, 2003).
