Decompensated liver disease and cirrhosis are common pathological states present on the gastroenterology ward. It is important to understand the basic principles of management and aetiology as a junior doctor in these complex and unwell patients.
Dr Liz Sweeney is a specialist hepatology registrar at the Royal Liverpool Hospital. In this episode, she talks to us about decompensated liver disease and cirrhosis with key advice to junior doctors working in hospitals3.
Or take it with you:
Let’s use a case as an example:
Mr BR is a 54 year old gentleman who has been referred by his GP to AMU with abdominal swelling and vomiting with skin discoloration. He has a past medical history of type 2 diabetes, cirrhosis and hypertension.
How would you start assessing a patient like this?
- HR 110
- BP 134/78
- Temperature 37.2
- RR 20
- SpO2 96% on room air
What is Decompensated Liver Disease?
Decompensated liver disease is defined as the presence of a deterioration in liver function in a patient with cirrhosis, which presents with:
Mr BR has presented with 2 of the above signs on examination. Therefore, your differential diagnosis of decompensated liver disease should be high on the list.
Why do patients decompensate with underlying liver disease?
There are multiple reasons why these patients decompensate and it is important to exclude some of the common predisposing factors whilst assessing these patients.
Portal vein thrombosis
Bacterial infections are one of the most frequent complications in cirrhosis and represent the main trigger for chronic liver disease patients entering a state of decompensation. Current prevalence ranges between 25% and 30% and is responsible for 30-50% mortality in these patients1. This is largely due to patients having cirrhosis-associated immune dysfunction (CAID) which places patients at high risk of opportunistic infections and more prone to developing common infections e.g. urinary tract infections and pneumonia. Therefore, a FULL septic screen including an ascitic tap (if confirmed ascites on either clinical examination or confirmed on imaging) is imperative during assessment.
It is important to ask patients about any new medications/dosage changes e.g. benzodiazepines or opioids that have been initiated to predispose to development of encephalopathy. Chronic liver disease patients are placed at an increased risk of both thrombosis and hepatocellular carcinoma (HCC). Therefore, assessment for portal vein flow with liver uss doppler can indentify any portal thrombus and an abdominal USS can identify any new liver lesions. These tests in association with measuring tumour markers (alpha-fetoprotein for HCC) can provide speculative diagnosis for a new hepatocellular carcinoma.
The following investigations are important to order on admission for a patient with decompensated liver disease:
Clotting profile– important determinant of liver synthetic function and measure for evidence of coagulopathy. However, these tests do not reflect the actual coagulation status for these patients and they may be at increased risk of thrombosis DESPITE derranged coagulation studies.
Nutritional bloods– these include all electrolytes (U&Es, Mg, calcium profile) and with the importance of measuring phosphate, albumin and protein too.
Full septic screen– urine dip and MSU, blood cultures (EVEN if not pyrexial, since these patients do not necessarily mount an immune response), chest x-ray and ascitic tap (if evidence of ascites).
USS abdomen– to assess liver parenchyma for evidence of cirrhosis, identify any new liver lesions, splenomegaly (indicating portal hypertension and therefore evidence of cirrhosis) and any ascites. Also, ensure you assess for the patency of portal vein flow via uss liver Doppler.
Although, it is important to realise that investigations will depend largely on the presenting symptoms. For example, CT head may be indicated if there is evidence of acute confusion, trauma, GCS drop given these patients can suffer from coagulopathy and thrombocytopenia (please refer to acute alcohol withdrawal written podcast for more info).
How do you manage these patients?
Initial management should be to stabilise your patient with an A-E approach alongside initiating certain treatment regimes in decompensated liver disease patients. Please refer to the excellent decompensated care bundle published by the British Society of Gastroenterology on a checklist guide for acute management2.
Any history of alcohol excess/alcoholic liver disease? -> Always place patients on IV thiamine EARLY (pabrinex 2 pairs TDS) even if on oral thiamine, and place patients on a reducing benzodiazepine detox regime e.g. chlordiazepoxide. *please listen to our acute alcohol withdrawal podcast for more info*
Once you have taken the full septic screen it is often prudent to initiate broad spectrum antibiotics for sepsis of unknown origin (e.g. IV tazocin-although refer to your local guidelines). Some evidence suggests the use of oral antifungals (e.g. fluconazole 100mg OD) in early assessment in conjunction with IV antibiotics, although we recommend seeking senior specialist advice prior to this. It is then important to manage patients according to their decompensated clinical presentation:
Encephalopathy – a spectrum of neuropsychiatric abnormalities as a result of liver failure which may present gradually or suddenly. It is important to assess a patient’s orientation and screen for any personality changes in the collateral history, as well as examining for a hepatic flap also known as asterixis.
Grading is used to decipher the degree of encephalopathy according to the West Haven criteria3
Grade 0: Subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, co-ordination.
Grade 1: Mild confusion, euphoria or depression, decreased attention, slowing of ability to perform mental tasks, irritability, inverted sleep cycle.
Grade 2: Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation.
Grade 3: Somnolent but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, incomprehensible speech.
Grade 4: coma, with or without response to painful stimuli.
Sometimes the evidence of covert hepatic encephalopathy is unclear and some clinicians support the use of testing serum ammonia levels and conducting EEG studies to help validate your judgment. However, these tests have been shown to sometimes provide poor correlation with clinical judgment with inconsistent accuracy4
Pathophysiology underlying hepatic encephalopathy is complex!5
As a basic understanding, in normal physiology there is a gradual build up of nitrogen-containing waste compounds from the intestine (mostly ammonia) that are transported to the liver to become metabolized through the urea cycle. Patients with cirrhosis have impaired liver function and thereby hepatocytes cannot metabolize the nitrogenous waste products. The most important waste product is ammonia which subsequently enters the systemic circulation and crosses the blood-brain barrier to become absorbed by cerebral astrocytes. Astrocytes use ammonia which causes an increase in osmotic pressure and increased GABA activity leading to the clinical manifestations of encephalopathy.
Therefore, understanding the basic pathophysiology principles we can evaluate the risk factors for developing encephalopathy. Ultimately excessive nitrogen load within the intestines will cause excess ammonia production to worsen encephalopathy and is why it is important to ask about bowel habit and whether any new medications e.g. opioids have been taken to predispose to constipation and cause acute encephalopathy.
Causes of hepatic encephalopathy:
- Excessive nitrogen load: consumption of large amounts of protein, GI bleed, renal failure, constipation
- Electrolyte disturbance: hyponatraemia, hypokalaemia
- Drugs: benzodiazepines, antipsychotics, alcohol intoxication
- Infection: pneumonia, urinary tract infection, spontaneous bacterial peritonitis etc
All patients who are acutely confused or suspicious of developing encephalopathy should have regular lactulose and phosphate enemas prescribed. This ensures that nitrogenous waste products are removed earlier before they can enter the systemic circulation. Interestingly, lactulose is the laxative of choice since evidence has shown it helps trap ammonia in the colon and uses gut flora to acidify the colon and transform ammonia into ammonium was cannot enter the systemic circulation5. Also, stool chart monitoring is important for documenting frequency of bowel motions, aiming for 3 or more bowel motions each day in order to prevent any accumulation of ammonia and worsening encephalopathy.
Ascites – important to exclude intra-abdominal infection (spontaneous bacterial peritonitis (SBP)) and therefore early ascitic tap on admission is important. If ascites develops to cause significant dyspnoea or abdominal discomfort, then large volume paracentesis can be conducted as symptomatic relief – however again discuss with specialists prior to considering an ascitic drain, especially if there is concurrent SBP.
What is the significance of coagulopathy?
Often these patients can have significant clotting dysfunction with sky high PT, INR and APTT values to be of concern to doctors for increased bleeding risk. HOWEVER, it is important to note that large volumes of research have demonstrated that these patients are in truth balanced delicately between procoagulant and anticoagulant factors. The liver produces many natural anticoagulant products (protein c, protein S and antithrombin III) and therefore in severe liver disease, the synthesis of these products are impaired in conjunction with all the other natural clotting factors produced by the liver6. Therefore, if patients are not actively bleeding and patients platelet count is >50, it is important to still give VTE prophylaxis e.g. fragmin to prevent clot formation since patients immobility places even greater risk given of VTE. *n.b please refer to your local VTE guidelines and always consult a senior before prescribing*.
Interestingly, research has shown that the severity of anticoagulant deficiency is proportional to the severity of liver disease and highlights the importance of VTE prophylaxis in these patients7.
Causes of Cirrhosis
There are many! Below is a helpful diagram listing some of the common causes of cirrhosis. Importantly, the commonest causes in the western world are alcoholic liver disease and chronic hepatitis C, followed by Nonalcoholic steatohepatitis (NASH) and chronic hepatitis B8.
Child’s Pugh scoring system is a useful quantitative analysis to determine the severity of liver disease when patients are in a compsenated state. Importantly, research has shown that severity of liver disease as determined by Child Pugh stage correlates closely with survival time with 100% one year survival with class A vs 45% with class C9
n.b. compensated cirrhosis refers to the preservation of hepatic synthetic function and no evidence of complications related to portal hypertension e.g. bleeding/jaundice/ascites
Handy mnemonic for remembering elements of the child pugh scoring system:
“Pour Another Beer at Eleven” for PT, Ascites, Bilirubin, Albumin, Encephalopathy.
What is the significance of renal impairment in decompensated liver disease?
Research has shown that between 20-50% of patients who present with decompensated cirrhosis also have a concomitant acute kidney injury (AKI)10. The management of severe renal dysfunction can be profoundly difficult and expert opinions from nephrology and hepatology specialists are key. It is important to note that the majority of causes for AKI are pre-renal with an evidence showing figures of around 49% in cases11. Therefore, even given 3rd space extracellular losses of fluid with ascites, it is important to adequately rehydrate patients to expand circulating intravascular volume and improve renal perfusion and thus function. Once you have given aggressive IVF resuscitation, and the renal function continues to deteriorate, it is appropriate to conduct further screening for the causes including: serum renal screen, USS KUB, urine dip and albumin/creatinine ratio (ACR) *please listen to AKI podcast for more info (Part 1/Part 2* and involve the nephrology specialists. THEN, once the cause for renal dysfuction is still not apparent with further deteriorating renal function, it is likely that you are dealing for hepatorenal syndrome (HRS).
What is hepatorenal syndrome?
This is a life-threatening medical condition with rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. The main pathophysiological basis behind the development of HRS is systemic arterial vasodilation, especially in the splanchnic vascular bed, leading to a decrease in arterial blood volume with activation of the renin-angiotensin-aldosterone system (RAAS) and further intrarenal arterial vasoconstriction worsening renal perfusion and therefore function 12. There are 2 types:
Type 1– characterized by rapid progressive kidney failure with increasing serum creatinine to level greater than 221mmol/L or halving creatinine clearance to less than 20mL/min over a period of less than 2 weeks.
Type 2-Slower onset and progression greater than 2 weeks with an increase in serum creatinine to 133>mmol/L or a creatinine clearance of less than 40mL/min.
It is important to note that type 1 HRS has a dreadful prognosis, with a mortality of 50% two weeks after diagnosis, approaching 100% within months 13. Therefore, early recognition and management is pivotal for survival. Type 2 HRS has a lower mortality rate with the median survival being approximately 6 months.
How is this treated?
HRS is extremely difficult to manage and treat! Recent evidence has shown that the use of IV albumin can improve renal function. The actual quantity and regime recommended varies considerably, but evidence has shown that 1g albumin/kg IV on day one followed by 2-40g/daily helped significantly improve renal function 14. After adequate rehydration, vasopressin analogues such as Terlipressin can be utilized to aid with splanchnic vasoconstriction and therefore improve renal perfusion and function. Often, very small doses such as 0.5mg QDS are commenced and titrated accordingly. However, given the complexity of this condition and poor prognosis, consultant led treatment advice is often employed. N.b. it is important to consider patient’s co-morbidities e.g. any vascular pathology/peripheral vascular disease since the use of Terlipressin may be contraindicated due to the risk of gangrene and peripheral necrosis.
It is important to find the CAUSE of ascites prior to acute treatment, which includes an ascitic tap for microscopy, culture, cytology and may include further radiology e.g. USS abdomen or CT abdomen. Once the cause has been identified, it is important to remove any predisposing worsening factors e.g. in alcoholic liver disease cirrhosis with ascites, it is firstly important to educate and promote drinking abstinence. N.b. the development of ascites indicates progression of the underlying cirrhosis and is associated with a 50% 2-year survival rate 15.
In addition, other conservative methods must be employed, such as the involvement of a dietician and patient education on the importance of a low salt diet (<88mmol/d) 15. Since the hallmark of the underlying pathophysiology is sodium (Na+) and water retention, sodium dietary restriction is therefore the cornerstone of management. Often patients will require initial medical management of their ascites in addition to conservative measures mentioned. This is in the form of DIURETICS. The two main classes of diuretics used for the treatment of ascites: loop diuretics e.g. furosemide and potassium sparing diuretics e.g. spironolactone. The loop diuretics act by inhibiting chloride reabsorption in the thick part of the ascending loop of henle, whereas K+ sparing drugs increase Na+ reabsorption in the distal tubule.
The pathophysiology underpinning cirrhosis and ascites leads to the activation of the RAAS and aldosterone. Therefore, aldosterone antagonists e.g. spironolactone 100mg OD are often first line. When loop diuretics are initiated with spironolactone, loop-acting diuretics and distal-acting diuretics have a synergist effect on renal Na excretion. It is important to conduct daily fluid balance measurements and daily weights to quantify any diuresis. The goal is weight loss of no more than 1kg/day for peripheral oedema and ascites and 0.5kg/day for ascites alone 16.
If maximal medical management in conjunction with conservative measures are not controlling the buildup of ascites, then large volume paracentesis (LVP) can be carried out for therapeutic drainage of ascites. This is where an ascitic drain catheter is left in situ for a maximal time (roughly 6hrs) or until drained to dryness. It is important to replace fluid lost with IV albumin (often 100mls 20% HAS for every 2L drained to help prevent post-procedural complications from large shifts of intravascular volume) and monitor U&Es and observations after the procedure 17. However, please always consult your seniors and seek specialist advice prior to attempting these procedures given patient complexity with associated coagulopathy and thrombocytopenia! Last resort methods of managing ascites, include the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), peritoneovenous shunts, and liver transplantation.
Treatment modalities for ascites:
Conservative: salt restricted diet, alcohol abstinence, healthy diet and exercise
Medical: diuretics (loop and K+ sparing)
Surgical/procedural: Large volume paracentesis (LVP), TIPS, peritoneovenous shunt.
What constitutes a non-invasive liver screen?
Deranged LFTs are a very common finding in AMU and ED, with further investigations needed to determine the underlying cause for this derangement. As a broad initial screening for deranged LFTs, an abdominal USS, clotting profile and full non-invasive liver screen (listed below) is a good foundation to determine the cause for the acute derangement.
Decompensated liver disease is a complex, common presenting complaint to the emergency department. These patients can become acutely unwell VERY quickly, therefore prompt A-E assessment, followed by a full history, examination and investigations will help determine the cause for the decompensation. The features for decompensation include: Jaundic, Coagulopathy,Variceal haemorrhage, Ascites and Hepatic encephalopathy. Published national guidelines recommended by the British Society of Gastroenterology provide an excellent guide for junior doctors on the acute investigations and management principles.
Again, given the patient complexity and high mortality associated with these patients, it is highly advisable that early involvement of a specialist herpetologist is key to successful management.
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