Introduction

Patients with liver disease are common in the UK. Since 1970, mortality from liver disease has quadrupled. It has become the greatest cause of death in people aged between 35-49 years old¹. It is important you know how to manage these patients in the medical take or on general medical wards and are aware of the complexities of their management. 

Definitions & Aetiology

Cirrhosis is the end stage of chronic liver disease and is defined as a diffuse pathological process, which is when normal liver parenchyma fibroses and converts to structurally abnormal nodules called regenerative nodules. This architectural distortion can lead to portal hypertension, and liver failure increasing the risk of hepatocellular carcinoma.

Unfortunately, it is generally irreversible in its advanced stage however by treating the underlying cause patients can show significant recovery². Most patients present at a later stage when it is too late for lifestyle or medication interventions¹.

It is often associated purely with alcohol, and patients with liver disease often feel stigmatised¹.

The causes of liver cirrhosis include viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease (NAFLD)³. NAFLD is quickly becoming the most common cause of chronic liver disease and liver failure. Combinations of factors can accelerate the process, e.g. An obese patient drinking alcohol above recommended levels. ⁴

Stages of liver disease

Cirrhosis is generally characterised by two staging systems – the Child-Pugh and the Model of End Stage Liver Disease (MELD) or the United Kingdom Model for End Stage Liver Disease (UKELD).

Criteria are met and scored for if the patient has ascites, hepatic encephalopathy, raised bilirubin, hypoalbuminaemia and deranged clotting. 

Child Pugh is split into A, B and C which correlates with increasing disease severity.

Grades of Encephalopathy and how to diagnose it will be discussed further down.

Child-Pugh A has a score of 5-6 points, Child-Pugh B has a score of 7-9 points and Child-Pugh C has a score of 10-15 points.

A Child-Pugh A patient has a survival of 100% at 1 year. This decreases to 80% for Child-Pugh B and falls to 45% for Child-Pugh C patients⁵.

Compensated vs Decompensated

Liver disease can also be split into compensated and decompensated. Patients with compensated cirrhosis often have no signs or symptoms, however, they can have asymptomatic varices (gastric or oesophageal) caused by portal hypertension. Compensated cirrhosis has a much higher survival rate (95% at one year). 

Decompensated liver disease can manifest complications of portal hypertension. These include ascites, hepatic encephalopathy, jaundice or variceal bleeding. These patients should all be managed by a Gastroenterologist. Survival rates for decompensated liver disease at one year are around 61%.

Child-Pugh A is classed as compensated liver disease. Child-Pugh B and C are classed as decompensated liver disease.⁶ 

Approach to the patient

Most commonly you will be managing a patient with known chronic liver disease and this is what I’m going to focus on. Information on how to interpret arranged LFTs is available in another article. A low index of suspicion is required.

History

Generally, you would do your usual full clerking with some specific questions

• Increasing abdominal distension (ascites)
• Any haematemesis or melaena or associated upper GI symptoms
• Confusion, brain fog, reversal of circadian rhythm
• Jaundice, Itch
• Peripheral oedema
• Do they drink alcohol, if so how much?
• Shortness of breath
• Constipation

Patients often present with non-specific symptoms

• Falls
• ‘Generally Unwell’
• Weight loss
• Decline

Examination

Patients with chronic liver disease may have any of these ‘chronic’ signs (not exhaustive)

• Spider naevi
• Palmar erythema
• Leukonychia
• Dupytrens contracture
• Bruising
• Distended epigastric vessels
• Gynaecomastia 
• Hepato/splenomegaly

In an acutely unwell liver patient, you should examine their respiratory, cardiovascular and abdominal systems specifically looking for jaundice, encephalopathy, ascites and any signs of bleeding – which may include a PR examination. 

Examining for hepatic encephalopathy (HE)

HE is a reversible impairment of neuropsychiatric function in conjunction with impaired hepatic function. This is due to a build-up of nitrogenous compounds absorbed from the gut, which are unable to be excreted by the impaired liver. These nitrogen-rich compounds are able to cross the blood-brain barrier.

Patients affected by HE have clinically apparent impairments in cognitive and neuromuscular function. Survival after presenting once with HE is 40% at one year and 20% at 3 years. ¹⁰

Examining for HE is very important and there is no specific laboratory or imaging test which can confirm or exclude it, it is not common practice for Gastroenterologists to perform serum ammonia levels.

History is imperative and a wide range of neurological and psychiatric symptoms can be present. These include memory issues, variable emotions, behavioural alteration, decreased energy levels, impaired cognition and sleep cycles. 

The most agreed upon examinations include testing for asterixis, which can be detected in patients in early to mild stage HE. To perform this examination, the patient extends their arms and dorsiflexes their wrists and holds this position. A positive test is an involuntary flapping tremor. In patients too drowsy for these tests, you can use oscillating grip strength are another way to test for asterixis.⁷

Grades of encephalopathy are shown below as per West-Haven Criteria:

Grade 0: Slightly abnormal on psychomotor analysis. No clinical manifestation.

Grade 1: Some mild confusion, behavioural alteration, sleep disturbance, slurred speech

Grade 2: Lethargy and moderate confusion

Grade 3: Incoherent speech, stupor and sleeping

Grade 4: Coma, unresponsive

Other investigations include psychometrics tests which have yielded a high sensitivity and low-cost rate, but results can vary depending on patient age and education. One that can be very useful is the ‘Animal Naming Test’.⁸

Investigations

Any patient presenting with decompensated liver disease (known or otherwise) should be investigated and treated according to the British Society of Gastroenterology ‘BASL bundle’⁹

https://www.bsg.org.uk/wp-content/uploads/2019/12/BSG-BASL-Decompensated-Cirrhosis-Care-Bundle-First-24-Hours.pdf

Initial investigations should include;

• A full septic screen – on all patients
  • Blood cultures – On all patients regardless of pyrexia/symptoms
  • Urine dip and culture
  • Chest X-ray
• An ASCITIC TAP – irrespective of clotting parameters! –
  • Sent for Cell count
  • Gram stain
  • Culture – at least 10ml in each blood culture bottle
  • Fluid albumin/protein
• Blood tests including LFTs and coagulation, Calcium, Magnesium & Phosphate
• Capillary blood glucose monitoring
• Abdominal USS – Assessing for focal liver lesions, portal vein thrombus, biliary pathology
• A recent alcohol history is imperative

Treatment

• Alcohol Withdrawal

If the patient drinks alcohol then a withdrawal chart (CIWA, GMAWS) should be commenced with lorazepam

• Wernicke’s Encephalopathy

IV Pabrinex 2 pairs TDS should also be prescribed as these patients are at risk of Wernicke’s encephalopathy, this should be continued for at least 3 days.

• Infection

If an infection is suspected, then treat with appropriate antibiotics according to local guidelines.⁹

Spontaneous Bacterial Peritonitis (SBP)

SBP is a common complication (10 – 30%) of hospitalised patients with ascites due to chronic liver disease and requires prompt diagnosis and initiation of appropriate antibiotics and intravenous human albumin solution.

Translocation of gut bacteria into the ascitic fluid is the proposed route for spontaneous/primary bacterial peritonitis. Secondary bacterial peritonitis may be due to perforated abdominal viscera or iatrogenic complications. 

Mortality has improved over the years. When first discovered mortality was as high as 90%; however with improvements in recognition and management, this now stands at around 20-30%. Whilst longer-term (>1yr) survival in the UK remains poor at ~34% in those that are treated transplantation should be considered if fit enough.

Administration of human albumin solution (HAS) in SBP reduces the incidence of renal failure by 72% and mortality by 47%. The number needed to treat to prevent one death is around 5 in SBP. 

It is important to administer albumin as per accurate dry weight. It can often be difficult to be accurate in patients with large volume ascites or extremes of weight e.g. Non-Alcoholic Fatty Liver Disease (NAFLD). Basing upon ideal body weight in these circumstances is often best.

In those who are grossly obese, it may be better to employ a more cautious approach with regard to albumin administration. It is much easier to give more albumin than it is to treat pulmonary oedema.

A 500ml bottle of 5% HAS contains the same amount of albumin as a 100ml bottle of 20% HAS, 20 grams. More often than not degree of volume dictates using 20% HAS.

Following a diagnosis of SBP, albumin should be given over an initial 6-hour period (Day 1). This is administered at a dose of 1.5g/kg. On Day 3 (i.e. 48 hours later) albumin is administered at 1g/kg.¹⁰

Acute Kidney Injury +/- Hyponatraemia

AKI is defined as an increase in serum creatinine ≥ 26μmol/L within 48hrs or ≥50% rise in serum creatinine over the last 7 days or Urine output (UO) <0.5mls/kg/hour for more than 6 hours or Clinically dehydrated

Hyponatraemia is defined as a serum sodium <125mmol/L

These patients should be treated with the following;

• Suspend all nephrotoxic drugs including diuretics
• Fluid resuscitate with either 0.9% sodium chloride or 5% Human Albumin Solution with 250mls boluses and reassessment between, aiming for a urine output >0.5ml/kg – although this is often not achieved – and a MAP (mean arterial pressure) of >80mmHg
• Accurate fluid balance
• If the patient has not improved to the above parameters within 6 hours, consider escalation to a higher level of care

Gastrointestinal (GI) Bleeding

If the patient has clinical or biochemical evidence of GI bleeding and known liver disease, variceal haemorrhage should be considered.

These patients should be treated as follows;

• Fluid resuscitate according to blood pressure, heart rate and Mean arterial pressure
• Administer IV terlipressin 2mg four times daily
  • Caution in those with significant peripheral, cardiac or cerebral vascular disease
    • Reduces mortality by ~30%
• Prescribe prophylactic antibiotics as per local guidelines
  • This should be administered to all patients with cirrhosis regardless of the cause of bleeding
    • Reduces rebreeding rates (45%—>10%)
    • Reduces mortality (47%—>15%)
• If prothrombin time (PT) is prolonged then give vitamin K 10mg stat
• If PT >20 seconds then give FFP 4 units and discuss with Haematology
• If thrombocytopenic (platelets <50) then given 1 pool of platelets after discussion with haematology
• Transfuse with packed red cells if Hb <7.0g/L or uncontrolled bleeding or haemodynamically unstable 
• In those with large-volume haematemesis, consideration should be given to airway protection and the need for early intubation for endoscopy.⁹
  
• There is no role for Tranexamic acid in upper GI bleeding and its use is harmful to patients¹¹
• Escalate to a senior early for consideration of a higher level of care
• Refer for early endoscopy after resuscitation with haemodynamic stability.⁹

Encephalopathy

Look closely for a precipitant and treat accordingly!

These include infection & sepsis, GI bleeding, dehydration, AKI, alcohol consumption, constipation, and certain medications.

Prescribe lactulose 20-30ml QDS with or without phosphate enema aiming for 2 soft bowel movements per day.

Rifaximin is licenced for the prevention of encephalopathy. It is an antibiotic which inhibits ammonia production. NICE recommends Rifaximin for reducing the recurrence of episodes of hepatic encephalopathy in adults aged 18 and over.¹²

If there is clinical doubt regarding encephalopathy diagnosis a low threshold for CT imaging of the brain is recommended, to exclude other causes of confusion and reduced GCS. Patients can be frail, sarcopenic or intoxicated. The threshold for CT scanning is low, especially if there is thrombocytopenia present also.  

Other treatment considerations

Low molecular weight heparin for all patients unless contraindication. Patients with cirrhosis are at higher risk of VTE (venous thromboembolism) despite clotting parameters. Only withhold with good reason, which may include platelets <50 or active bleeding.

A Gastroenterology or Hepatology specialist review should ideally be sought within 24 hours of admission to the hospital.⁹

Nutritional support from a dietician, ideally with a specialism in liver disease, should also be sought quickly with full nutritional assessment and advice for commencing a high protein and low salt diet. and cirrhotic eating patterns.

Patient discussions

Escalation of care planning should be discussed with all patients. Guidance should be sought from an experienced Gastroenterologist.

Other advice should be discussed including alcohol abstinence, avoiding hepatotoxins such as NSAIDs and high doses of paracetamol, a low salt diet and adequate nutritional intake of carbohydrates and protein.¹²

References

1. The British Liver Trust (2019). The alarming impact of liver disease in the UK. https://www.britishlivertrust.org.uk/wp-content/uploads/The-alarming-impact-of-liver-disease-FINAL-June-2019.pdf
2. Anthony PP, Ishak KG, Nayak NC, et al. The morphology of cirrhosis: definition, nomenclature, and classification. Bull World Health Organ. 1977;55(4):521-40.
3. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):245-66.
4. Davis GL, Roberts WL. The healthcare burden imposed by liver disease in aging Baby Boomers. Curr Gastroenterol Rep. 2010 Feb;12(1):1-6.
5. Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85.
6. Thorton, K. Evaluation and Prognosis of Persons with Cirrhosis. Hepatitis C Online. 2021. Core Concepts – Evaluation and Prognosis of Persons with Cirrhosis – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online (uw.edu)
7. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60:715-35
8. Nabi E, Bajaj JS. Useful tests for hepatic encephalopathy in clinical practice. Curr Gastroenterol Rep. 2014 Jan;16(1):362. doi: 10.1007/s11894-013-0362-0. PMID: 24357348; PMCID: PMC3918211
9. McPherson, S. Dyson, J. Austin, A. Hudson, M. BASL Decompensated Cirrhosis Care Bundle. The British Society of Gastroenterology. 2014. https://www.bsg.org.uk/wp-content/uploads/2019/12/BSG-BASL-Decompensated-Cirrhosis-Care-Bundle-First-24-Hours.pdf
10. Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O’Brien AJ, Verma S. Guidelines on the management of ascites in cirrhosis. Gut. 2021 Jan;70(1):9-29. doi: 10.1136/gutjnl-2020-321790. Epub 2020 Oct 16. PMID: 33067334; PMCID: PMC7788190
11. NICE Technology Appraisal guidance – TA337 (March 2015; reviewed June 2018): Rifaximin for preventing episodes of overt hepatic encephalopathy.

Written by Ailsa Gemmell, IMT3
Reviewed by Christopher Kelly, ST4 Gastroenterology