Cirrhosis is the term given to permanent damage of the liver cells. Damage can be caused by alcohol, Hepatitis B, Hepatitis C or autoimmune disorders such as autoimmune hepatitis, amongst other factors. Continuous insults to the liver result in the formation of collagenous scar tissue which replaces the previously injured tissue and is called liver fibrosis. Cirrhosis is an advanced stage of liver fibrosis with the addition of distorted hepatic vasculature.
Asymptomatic cirrhosis is termed ‘compensated cirrhosis’, whereas development of symptoms associated with cirrhosis is referred to as ‘decompensated cirrhosis’. Symptoms can include:
- Jaundice
- Ascites
- Hepatic Encephalopathy (HE)
- Varicies
Between five and seven percent of patients move from a compensated to a decompensated state every year. Decompensated cirrhosis is considered a systemic disease with multi-organ dysfunction, and the median survival of these patients is reduced from 12 years to two years.
Triggers of decompensated cirrhosis include:
- Continual insult to the liver by alcohol or virus
- Bacterial Infection
- GI Bleed
- Dehydration
- Renal dysfunction
The pathophysiology of a decompensated cirrhotic
Haemodynamic disturbances and hyperdynamic circulatory syndrome (peripheral arterial vasodilation), mainly spanchnic circulation seen in a decompensated patient, put the individual at risk of developing ineffective volaemia which will result in hypo-perfusion. The kidneys are the most commonly affected organs that suffer from the hypo-perfusion. Where there is ineffective volaemia, vasoconstriction and water and sodium retention mechanisms kick in. These systems include the renin angiotensin aldosterone system (RAAS), sympathetic nervous system and arginine-vasopressin secretion. This may contribute to renal retention of sodium and water which can cause ascites and hepato-renal syndrome (HRS).
Haemodynamic abnormalities include:
- Hepato-pulmonary syndrome (HPS)
- Increased susceptibility to shock
- Decreased cardiovascular responsiveness to physiological and pharmacological vasoconstrictive stimuli
Cardiac dysfunction due to cirrhotic cardiomyopathy can occur in advanced stages of decompensation. Cardiomyopathy results in the heart not being able to increase its cardiac output to sufficiently comply with the needs of systemic circulation.
There are also molecular mechanisms that take place that cause vasodilation. There is an enhanced production of endothelia vasodilating substances, including nitric oxide, carbon monoxide and prostacyclin.
Decompensated cirrhosis is a systemic disease with multi-organ dysfunction. The median survival of patients is two years.
The primary cause of decompensated cirrhosis is a state of chronic inflammation secondary to increased pro-inflammatory cytokines and chemokines. This is caused by a spread of bacteria and bacterial products called ‘pathogen associated molecular patterns’ (PAMPs) resulting from bacterial translocation.Bacterial translocation causes changes in the microbiome and increases intestinal permeability.‘Danger associated molecular patterns’ (DAMPs) are released by the liver due to local inflammation and cell apoptosis and necrosis. PAMPs and DAMPs bind with immune cells producing and releasing pro-inflammatory molecules, reactive oxygen and nitrogen species, which all result in circulatory dysfunction and multi-organ failure.
Liver ITU admission and management of a decompensated patient
Patients are brought to the Liver ITU to treat the decompensation and work towards moving the patient into a compensated or stable state where they are then ready to be stepped down to a ward.
The medical team will aim to identify and suppress aetiological factors that have caused inflammation, cirrhosis or decompensation. On admission to LITU, patients will often be started on broad spectrum antibiotics +/- antifungals depending on their risk factors. Throughout the course of a patient’s stay, all antibiotic and antifungal use should be reviewed and adjusted according to their clinical needs.
Any presence of Hepatic Encephalopathy (HE) will be assessed and treated as appropriate. Patients with higher grade HE will be sedated and intubated to protect their airway. Often an ammonia level will be taken and higher levels treated as appropriate. As mentioned above, vasodilation associated with a decompensated state can occur and result in a patient needing one or two vasopressors titrated to a target MAP (mean arterial pressure).
All patients will have their renal function reviewed to assess for an acute kidney injury associated with hypo-perfusion or HRS. A decision will be made regarding the need for continuous renal replacement. Patients thought to have HRS may be initiated on bolus doses of terlipressin and albumin.
All patients will be assessed for their need for pabrinex and a proton pump inhibitor (PPI) which are reviewed daily according to their clinical need. Any signs of bleeding may require an endoscopic procedure to look for varicies and band any that might be found. Raised portal pressures can be managed with b-blockers when appropriate to prevent further variceal bleeds. In addition, the patient’s coagulation will be assessed, and venous thromboembolism prevention addressed as needed.
As a patient improves, many of the treatment strategies will start to be removed. The patient will be extubated and, where appropriate, initiated on preventative HE measures. Vasopressors will be removed and where necessary b-blockers introduced or re-introduced. Patients will be taken off continuous renal replacement and assessed for a need for intermittent renal replacement when on the ward. PPIs will be continued or reduced as needed and a nutrition plan put in place.
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Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
