• Chronic conditions

We read, with great interest, Dr Gola et al's1 manuscript entitled “Economic analysis of costs for patients with end stage liver disease over the last year of life”, in which the authors clearly demonstrated the increased economic burden of end stage liver disease (ESLD) on health systems. This original article should not be considered only a mere analysis of costs related to ESLD but also as a starting point for future directions in this field.

Liver cirrhosis is the common result of different injuries to liver tissue, leading to necroinflammation and neofibrogenesis. The prognosis of patients with chronic liver disease varies widely, depending on the presence of portal hypertension, the clinical stage, the removal of the underlying pathogenetic noxa (ie, alcohol, hepatitis C virus) or the occurrence of decompensation and other clinical events (ie, infections, kidney injury).

Quality of life results reduced in almost all patients with cirrhosis because of an impairment in all the three areas of health-related QoL (HRQOL), namely, physical, psychological and social; despite these evidences, the assessment of HRQOL is frequently a marginal issue in the clinical evaluation of the patient with cirrhosis. The stage of the disease, age (older), gender (female) and cultural and socioeconomic issues significantly influence patients’ QoL. Patients with compensated disease present different morbidity conditions, compared to those with decompensated cirrhosis; in particular, non-life-threatening symptoms (ie, fatigue, cachexia, muscle cramps, itching) and subclinical or covert hepatic encephalopathy impair patients’ perceived health status. Finally, not only patients but also caregivers present psychological issues (anger and anxiety) more frequently than healthy controls, matched for age, sex and socioeconomic conditions.2

Together with the progression of liver disease, the development of decompensation significantly impairs patients’ physical and psychological status. For example, patients with ascites could report abdominal pain (discomfort/distension), nausea and vomiting, early satiety and dyspepsia, distal oedema, constipation or even dyspnoea; moreover, decompensated patients (ie, ascites, variceal bleeding, systemic infections, hepatic encephalopathy), frequently require hospitalisation and present increased mortality.

It is widely accepted that, in the case of chronic disease with impaired QoL, it is mandatory to assess and even treat every other unbearable symptom; however, the relationship between curative and palliative care, especially in the case of non-malignant disease, is a key issue. For oncological patients, the withdrawal of cancer treatments (chemotherapy or radiotherapy) is sometimes a less difficult decision, based on disease progression, deterioration of patient's performance status or development of significant side effects. In every chronic disease, PC cannot replace curative treatment and the integration of these should take place as soon as possible.

In the case of cirrhotic patients, even the management of analgaesic drugs is complicated by concomitant clinical and pharmacological alterations. Indeed, in these patients, ESLD drug metabolisation and elimination are significantly impaired because of reduced liver blood flow, parenchymal dysfunction and reduced plasma binding-protein. The liver plays a pivotal role in drug metabolism; it is responsible for oxidation or reduction reactions, conjugation (CYP450-dependent) and biliary elimination. At the final stages, cirrhotic patients may also present portosystemic shunt, which can lead to a further metabolism impairment. In any case, opioids could be safely managed to relieve pain and dyspnoea, and have to be considered the drugs of choice in the case of moderate-severe symptoms.

Finally, a reliable clinical prognostication in these patients seems almost impossible, leading to increasingly more trouble in identification of treatment goals and planning initiation of supporting care, especially for patients suitable for liver transplantation (LT). Indeed, the natural history of ESLD could be characterised not only by exacerbation and deterioration of general conditions, but also by stabilisation, or even improvement.3

Recent evidence suggested that PC and even access to hospice are indicated both for patients on the waiting list and for those not suitable for LT.4

LT remains the only curative treatment option, able to increase life expectancy and quality of life in patients with ESLD. The discrepancy between the increasing amount of patients requiring LT and the shortage of organs leads to an elevated ‘in-list’ mortality and higher rate of exclusion because of disease progression (ESLD or HCC); moreover, many patients cannot be considered suitable for LT because of comorbidities or some could also die because of LT complications. For these reasons, treatment goals have to be clearly identified, explained and shared with patients and caregivers; the failure of LT as an option should not coincide with the introduction of PC, which in this case would be experienced only as a palliation of the failure.

Moreover, organ allocation based on the severity of the underlying disease branded some patients as ‘to well for transplant, too sick for life’.

Given the costs of hospitalisation admission and stay, the risk stratification and identification of patients who will benefit from hospital admission appear to be necessary. In the case of progressive deterioration of liver and multiorgan functions, in patients not suitable for LT, the reassessment of the treatment goals and even starting of end-of-life care (EoL) care seems necessary.

Palliative care and hospice admission are still considered only as ‘non-curative’ approaches and therefore are usually neglected for patients listed for LT. Moreover, in Italy, hospice admission is considered as a surrogate of actively dying and is not taken into account for patients with potential curative treatment with long-term survival (ie, LT candidates). Therefore, it is not surprising that PC is underconsidered in this population. To date, a US study observed that only 11% of patients were referred to PC, even after denial of LT.5

All physicians have to keep in mind that palliative and curative treatments are not mutually exclusive, and active symptom management and psychological support also have to be introduced for patients with non-malignant disease. Moreover, the integration of PC (and/or timely hospice admission) into LT programmes could lead to a significant improvement of the quality in EoL care and reduction of healthcare costs. In our opinion, future studies have to evaluate if this integrated model could be considered the best possible care for LT candidates.