This document provides guidance on the management of:

Acute liver failure (ALF)

• Recognition

• Early management

• Tertiary referral criteria

Decompensated cirrhosis

• Clinical assessment and early management

• Therapeutic paracentesis

• Spontaneous bacterial peritonitis (SBP)

• AKI and Hepatorenal syndrome (HRS)

• Hyponatraemia

• Hepatic encephalopathy (HE)

Variceal bleeding is dealt with in its own separate guideline

Advice on analgesics

This is a controlled document. If you are using a printed copy, check it against the guidelines site to ensure you are using the latest edition. Print copies must be destroyed after use.

Abbreviations

Definition of acute liver failure (ALF)

ALF must be considered with acute derangement in LFTs (usually very high AST/ALT), associated with coagulopathy (INR >1.5), and any degree of mental alteration (encephalopathy). ALF can only be diagnosed in a patient without pre-existing cirrhosis and with an illness of < 28 weeks duration.

If these symptoms occur in a patient with pre-existing liver disease, the term acute-on-chronic liver failure is used, and is considered a separate diagnosis from ALF.

The only exceptions include acute presentations of chronic autoimmune hepatitis, Wilson disease and Budd-Chiari syndrome, which would be considered as ALF as they share a common clinical picture and prognosis.

The time taken to develop HE from the initial symptom of jaundice determines whether the patient has hyperacute liver failure (within 7 days), ALF (8-28 days) and subacute liver failure (within 5-12 weeks).

Aetiology of ALF

Common causes are paracetamol toxicity and viral hepatitis (full list in box 1). Paracetamol cases (‘hyperacute liver failure’) behave much more aggressively. Patients should be transferred to a high dependency environment. The aetiology of ALF is an important indicator for prognosis and treatment strategy, especially regarding need for emergency liver transplant.

Death can occur swiftly if ALF is not recognised, mechanisms including hypoglycaemia, deep encephalopathy with cerebral oedema and coning, circulatory failure and sepsis. Early referral to a transplant centre for assessment may be lifesaving.

Clinical assessment and early response:

Conscious level – 2 hourly monitoring. Contact anaesthetics if GCS <10 or evidence of Grade II or more encephalopathy (see Box 2 for grading). CT head if HE present to assess for cerebral oedema or other underlying pathology.

Blood glucose – Close monitoring and treat if low (infusions of concentrated dextrose 10-20%).

Circulation – ECG. Resuscitate with intravenous 0.9% Saline if shocked (avoid 5% dextrose, this may lead to hyponatraemia and exacerbate cerebral oedema). Correct electrolytes. Refractory hypotension will require vasopressor support in ICU, to preserve cerebral perfusion. Insert urinary catheter with hourly UO.

Temperature – hyperpyrexia should be treated with cooling.

Sepsis – CXR, blood and urine culture. Check for infected lines, skin sepsis.

Investigations:

• INR/PT and FBC

• Urea & Electrolytes/liver function tests (including AST, GGT)

• Phosphate/Calcium/Magnesium

• Pre-emptive group and save

• Arterial blood gas with lactate

• Arterial ammonia – High ammonia levels > 200 are more specific and may predict an increased risk of developing intracranial hypertension

• Amylase and Lipase (high incidence of pancreatitis in paracetamol cases)

• Paracetamol level (even if no clear history – Better to be sure)

• Viral: HAV, HBV, HCV, HEV, HIV, EBV, CMV, HSV, VZV

• Caeruloplasmin/urinary copper excretion

• Liver autoantibodies and immunoglobulins

• Urine toxicology screen

• Pregnancy test in females

• Liver USS with dopplers (? evidence of cirrhosis, infiltration), Consider CT if Budd Chiari suspected

• Liver biopsy is sometimes considered only after specialist hepatology review

Coagulation must be tested every 12 hours. FFP should NOT be given unless there is evidence of bleeding. The INR is critical in deciding who needs a transplant. Vitamin K can be given. This will not mask true coagulopathy.

When to refer to a transplant centre:

Established transplant criteria are used in specialist centres to identify transplant candidates. They are a useful guide but referring hospitals would ideally identify candidates before they get this severe.

Suggested criteria for referral of cases of ALF to specialist units

Essentially, any patient with a rising INR, encephalopathy, worsening renal function, acidosis, lactate or bilirubin despite initial measures is likely to need discussion.

Conditions that may impact upon the decision in respect to emergency liver transplant:

• History of chronic liver disease

• Active and dependent alcohol or substance misuse

• History of cancer in recent past

• Severe congestive heart disease or respiratory co-morbidity

Ward management:

Once established, ALF is not likely to respond to any particular therapy. Treatment is focused on avoiding/ameliorating complications.

A full medication review should be undertaken, including indications and dosing of all prescribed medications. Avoid sedatives, hepatotoxic and nephrotoxic drugs. Discuss with a pharmacist for further advice.

Consider stress ulcer prophylaxis.

Ensure volume replete and correct electrolytes.

Monitor and correct hypoglycaemia

Low threshold for empirically starting antibiotics if haemodynamic deterioration or worsening HE with inflammatory phenotype.

N-Acetylcysteine in ALF

There is some evidence that n-acetylcysteine (NAC) is beneficial in the early stage of ALL causes of ALF (not just paracetamol related)². NAC is a thiol containing agent that binds with free oxygen radicals and replenishes glutathione stores post hepatic injury to prevent further damage.

Indication: Hepatocyte protection in ALF (on advice of hepatologist).

Note: for treatment of paracetamol overdose, refer to the Trust guideline - the usual SNAP protocol dosing should be used.

 

Dose: 150mg/kg in 1000ml 5% Glucose over 24hours.

Dosing is based on actual body weight, but weight should be capped at maximum of 110kg.

On ICU or in severely fluid overloaded patients, dilute required dose in 250ml 5% glucose.

ICU management:

Management of refractory hypotension, coma/raised intracranial pressure and renal failure are outside the scope of this document; specific advice will be given by the transplant centre to which the patient has been referred.

Clinical presentations:

Patients can present with complications of known cirrhosis or with no previous diagnosis of cirrhosis. The diagnosis of cirrhosis is often possible just on clinical findings and a suggestive history (e.g. ascites, spider naevi, heavy drinking history).

Decompensated cirrhosis is a medical emergency with a high in-hospital mortality (10-20%). Effective early interventions can save lives and reduce hospital stay. It is defined as a patient with cirrhosis who presents with an acute deterioration in liver function that can manifest with the following symptoms:

• Jaundice

• Ascites (new onset or worsening)

• Hepatic encephalopathy

• Renal impairment

• GI bleeding

• Signs of sepsis/hypovolaemia

There is often a precipitant. Commonly they would include:

• Sepsis (e.g. chest, urine, SBP)

• GI bleeding (variceal or non-variceal)

• Dehydration (e.g. D&V, over-diuresis)

• Constipation

• Alcoholic hepatitis

• Acute portal vein thrombosis

• Development of Hepatocellular carcinoma

• Drugs (Alcohol, opiates, NSAIDs etc). A full medication review should be undertaken.

• Ischaemic liver injury (sepsis or hypotension)

Initial assessment should focus on looking for precipitating causes and treating them accordingly.

The BSG-BASL Decompensated Cirrhosis Care Bundle (Weblink: Decomp-care-bundle-(Figure-1).pdf) will guide you on the necessary investigations and early management of these patients and should be completed on EPIC for all patients admitted with decompensated cirrhosis within the first 6 hours of admission (Dot phase ‘DECOMPLIVERBUNDLE’).

Escalation of care to higher level should be considered in patients not responding to treatment or worsening EWS when reviewed after 6 hours, particularly in those with first presentation and those with good underlying performance status prior to the recent illness.

All patients with decompensated cirrhosis should have a GI/Liver specialty review ideally within 24 hours.

Clinical assessment and early management:

Conscious level – Monitor GCS. Contact anaesthetics if GCS < 8-10; Assess for asterixis (see Box 2 for hepatic encephalopathy grading); prescribe lactulose 20 – 30 ml QDS or phosphate enema if asterixis or drowsiness. (Aiming for 2 soft stools/day) – See Hepatic Encephalopathy section below. If any clinical doubt in a confused patient or if deteriorating GCS or focal neurology, request a CT head to exclude other intra-cranial pathology e.g. sub-dural haematoma

Circulation – Hypotension should be treated with IV crystalloid e.g. 0.9% sodium chloride (avoid dextrose in acute scenarios, this may exacerbate hyponatraemia and confusion) - 250 ml boluses with regular reassessment. 1-2L will correct most losses.

Kidneys – Fluid balance chart and daily weights, can often get rapid measure of electrolytes and renal function from point of care testing.

If AKI (increase in serum creatinine ≥ 26μmol/L within 48 hours, ≥50% rise in serum creatinine over the last 7 days, Urine output (UO) < 0.5 ml/kg/hr for more than 6 hours based on dry weight or clinically dehydrated) and/or hyponatraemia (Na <125 mmol/L):

• Suspend all diuretics and nephrotoxic drugs

• Fluid resuscitate with IV crystalloids as above (Aim for UO >0.5 ml/kg/hr on dry weight)

• Consider adding 20% HAS 1g/kg (max 100g) for plasma volume expansion if ≥ stage 1B AKI or confirmed infection for first 48 hours

• Regular review of fluid balance and response 6 – 12 hourly

• Screen for Intrinsic (e.g. ATN) and post-renal causes of AKI

• If not responding after 48 hours, consider HRS (see HRS section below)

Ascites – Diagnostic tap is mandatory and can be done irrespective of clotting parameters; one or two passes with a green needle is unlikely to cause harm despite coagulopathy; Ensure ascitic fluid sent in universal container bottles for fluid albumin, MCS and blood culture bottles (minimum 5 ml in each bottle) to maximise yield of SBP diagnosis; if polymorphonuclear cells >250/mm^3, diagnosis is SBP (see SBP section below)

Sepsis – check for all other potential sources; start empirical broad-spectrum antibiotics as per hospital guidelines after cultures taken if clinical evidence of infection.

Signs of bleeding – check for melaena with PR exam.

If evidence of GI bleeding and varices suspected:

• Fluid resuscitate according to pulse and blood pressure

• IV Terlipressin 2 mg QDS (ECG required and if contraindications present, discuss with GI bleed consultant and consider lower dose or octreotide) – Hold beta blockers if commencing

• Prophylactic IV Ceftriaxone 2 g daily.

• Target Hb 70-80 g/L. If massive bleeding, aim for Hb > 80g/L. Early endoscopy AFTER resuscitation (ideally within 12 hours)

• Correction of haemostatic tests with platelets, FFP, PCC and other products is not recommended in stable patients outside of those taking anticoagulants. Discuss with the Haematologists and GI bleed consultant if unstable.

• PPI not indicated for suspected variceal bleeding (increased risk of SBP and HE) unless suspecting possible non-variceal causes too

• Consider activating the massive haemorrhage protocol for unstable variceal bleeds

Contraindications to Terlipressin:

Absolute: Hypersensitivity, pregnancy, acute respiratory failure, septic shock, creatinine > 442 µmol/L

Relative: Age >70, PVD, prolonged QTc, cardiac arrhythmia, uncontrolled hypertension, ACS, previous MI

Where there are absolute contraindications to the use of terlipressin, consider octreotide 50microgram bolus followed by 25-50microgram/hr infusion.

Alcohol

• See separate guideline for alcohol withdrawal management

• Commence CIWA scoring

• Give IV Pabrinex (2 pairs of vials three times daily) or IV thiamine 500mg TDS if history of current alcohol excess

• Refer for alcohol specialist nurse review

• Monitor for refeeding syndrome

Other considerations

• IV vitamin K 10 mg daily for 3 days if PT prolonged

• Unless actively bleeding or platelet count <50, Prophylactic LMWH should be considered for VTE prophylaxis as patients with liver disease have a high risk of thromboembolism even with a prolonged PT.

• Referral to dieticians

• A full medication review should be undertaken, including indications and dosing of all prescribed medications. Avoid sedatives, hepatotoxic and nephrotoxic drugs. Discuss with a pharmacist for further advice.

• Other than for the indications mentioned in this guideline, albumin infusion is not beneficial in unselected hospitalised patient with cirrhosis e.g. solely to improve serum albumin levels⁶

Investigations:

• FBC, U+Es, clotting, LFTs (including AST, ALT, GGT), CRP, serum albumin, Ca/Phosphate/Magnesium, AFP, glucose

• Blood cultures, CXR, urine dip and MCS, stool for MCS and CDT if diarrhoea

• Blood gas to look for acidosis and lactate

• Ascitic tap if ascites - send for MCS, and culture as above. If first presentation of ascites, then also send fluid albumin and cytology

• Ultrasound liver with doppler of portal and hepatic vein

Specific complications of cirrhosis:

1. Massive ascites and therapeutic paracentesis

Consider this if patient in pain with tense ascites or there is respiratory compromise.

Not recommended in patients with untreated SBP (may exacerbate renal failure), although can still be considered in certain scenarios e.g. if causing significant respiratory compromise, with close monitoring. A limited paracentesis (<5L) with HAS cover may be more appropriate in patients at higher risk of renal failure.

Albumin replacement is required if > 5L of ascites is drained – this will usually be the case if the patient has massive ascites so generally should be prescribed with every drain.

The ascitic drain should not be left in for more than 6 hours.

Drains may be inserted by trained personnel on the ward without ultrasound guidance, with use of bedside ultrasound or by Radiologists under US guidance.

Regimen: 100ml 20% human albumin solution should be given for every 2.5 litres of ascites drained (obtained via blood bank)

2. Spontaneous Bacterial Peritonitis

SBP is diagnosed if the ascitic tap shows >250 polymorphonuclear cells/mm³.

A tap should be performed on all patients presenting with ascites (including a sample in blood culture bottles).

Some patients with SBP will develop renal dysfunction. Albumin (in conjunction with antibiotics) has been shown to reduce the incidence of renal failure and improve survival in patients at higher risk of renal dysfunction⁷.

Patients at risk of renal dysfunction in the setting of SBP are those with more severe liver disease. Review nephrotoxics, beta blockers and indication for any prescribed PPI.

Give albumin on day 1 and day 3 for patients diagnosed with SBP to prevent AKI

Regimen: 1.5 g albumin/kg on the day of diagnosis followed by 1 g/kg on day 3.

A 100ml bottle of 20% HAS contains 20g of albumin. Therefore, a 70kg patient will need 105g albumin on the first day = 5 bottles (to the nearest unit). On the third day will need 70g = 3-4 bottles.

Antimicrobial treatment: Refer to antibiotic policy on intranet.

Patients should start on long term prophylactic antibiotics (refer to antibiotic policy on intranet) afterwards to reduce risk of recurrent SBP.

3. Hepatorenal syndrome (HRS)

HRS is progressive renal dysfunction in cirrhosis not caused by another identifiable factor (essentially a diagnosis of exclusion). The terms type 1 HRS and type 2 HRS have been replaced by HRS-AKI (see criteria below) and HRS-NAKI respectively. This guideline focuses on the acute management of HRS-AKI. Patients with possible HRS should be discussed with the Hepatology team.

Renal dysfunction in cirrhosis is very commonly caused by something else, e.g.

• Dehydration (vomiting, diarrhoea, GI bleeding)

• Over-diuresis (e.g. previously prescribed for ascites)

• Nephrotoxic drugs (NSAIDs, aminoglycosides)

• Glomerulonephritis associated with cryoglobulinaemia in Hepatitis C

• IgA nephropathy in alcoholic liver disease

Therefore, once AKI has been diagnosed, the cause of AKI should be investigated as soon as possible as per AKI bundle (e.g. urine dip, albumin: creatinine ratio, renal tract ultrasound) and potential causes treated.

• Irrespective of the stage, diuretics and other nephrotoxic drugs should be discontinued

• Consider holding non-selective beta-blockers

• Screen and treat for infections, especially SBP if ascites present

• Volume replacement in accordance with cause and severity of fluid loss (e.g. crystalloids for patients with diarrhoea or excessive diuresis

• Treat acute GI bleeding and transfuse to maintain Hb 70-90 g/L

• In patients with AKI and tense ascites, therapeutic paracentesis should be associated with albumin infusion since it improves renal function.

The majority of patients (>90%) with AKI stage 1A (serum creatinine < 133 µmol/L) would be expected to respond to the above management within 48 hours with hypovolaemia being the most likely cause.

In patients with no obvious reversible cause with AKI stage >1A (serum creatinine > 133 µmol/L), 20% albumin solution at the dose of 1 g of albumin/kg of body weight (with a maximum of 100 g of albumin) should be given for two consecutive days.

In patients with AKI stage > 1A, who fail to respond to these measures and fulfil criteria for HRS-AKI, treatment with ALBUMIN (20 – 40 g/day) and Terlipressin is indicated (See dosing below)^8,9,10

Criteria for HRS-AKI:

• Cirrhosis with ascites

• Diagnosis of AKI (serum creatinine increasing ≥26.5 µmol/L within 48 hours or an increase in serum creatinine  ≥1.5 times from baseline within past 7 days)

• No response after 2 consecutive days of diuretic withdrawal and volume expansion with HAS

• Absence of shock

• No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides or iodinated contrast media)

• No signs of structural kidney injury (proteinuria > 500 mg/day, microhaematuria >50 red blood cells per high powered field and/or abnormal renal imaging)

More recently, terlipressin in the treatment of HRS-AKI has been linked to a higher risk of respiratory failure and sepsis and should therefore be used with caution⁵. In 2023, the Medicines and Healthcare products Regulatory Agency (MHRA) recommended new measures to reduce the risk of respiratory failure and sepsis related to using terlipressin in people with type 1 hepatorenal syndrome¹¹.

This included a warning to avoid terlipressin in patients with advanced acute on chronic liver failure (ACLF grade 3 and/or MELD >39) or advanced kidney failure (creatinine > 442 µmol/L) unless the benefit is judged to outweigh the risks. Patients with breathing problems should receive treatment to manage their condition before starting terlipressin. During and after treatment, patients should be monitored for signs and symptoms of respiratory failure and infection. If patients develop respiratory symptoms, dose reduction of human albumin if being used, should also be considered. If symptoms are severe or do not resolve, terlipressin should be discontinued.

In higher risk patients, both the MHRA and EASL guidelines recommend terlipressin as a continuous infusion as this may reduce the risk of severe side effects vs intermittent bolus administration^1,11,12

Terlipressin Dosing:

Intermittent Bolus Dosing.

Terlipressin 0.5mg-1mg qds*.* HAS 1g/kg on day 1 and 40g daily thereafter.

Dose of terlipressin can be increased to 2mg qds if renal function has not improved after 2-3 days.

Terlipressin continuous infusion (diluted in 5% dextrose):

1mg in 50mL (20micrograms in 1mL), 2mg in 100mL (20micrograms in 1mL), 5mg in 250mL (20micrograms in 1mL) - run over 24hours, adjusting dose according to response. 

Initially 2mg/24 hours. If no improvement in urine output (30% increase) or a significant decrease in serum creatinine (by 20-25 µmol/L) by 24-36 hours, then dose of terlipressin should be increased to 4mg/24 hours.

Terlipressin should be maintained until a complete response (creatinine < 133 µmol/L or within 26.5 µmol/L of baseline) and up to a maximum of 14 days in the case of partial response (improvement but > 133 µmol/L or 26.5 µmol/L from baseline) or non-response.

4. Hyponatraemia

Hyponatraemia is common in advanced liver disease and can be a marker of poorer prognosis and increased risk of HE and HRS. A careful history, assessment of fluid status, biochemistry and medication review are essential to determining the cause.

Diuretics and other potential medications, which may cause hyponatraemia, should be held.

Hypovolaemic hyponatraemia should be treated with fluid resuscitation with 0.9% saline and those with hypervolaemic hyponatraemia should be fluid restricted to achieve negative fluid balance (usually between 1 – 1.5L/day), unless there is AKI.

It is possible for patients with ascites, peripheral oedema and low serum albumin to still be intravascularly deplete, in which case use of HAS may improve serum sodium, but not mortality.

Correction of hyponatraemia should be by <8 mmol/L per 24 hours to avoid osmotic demyelination syndrome. Hypertonic saline is not routinely used as it can worsen fluid overload and increase risk of demyelination. It can be considered in the critical care environment in patients with life-threatening sequelae of hyponatraemia.

There is no role for Vaptans in the management of hyponatraemia secondary to decompensated liver cirrhosis.

5. Hepatic encephalopathy

Hepatic encephalopathy is a manifestation of hepatic decompensation, but can also occur in isolation without concomitant elevations in bilirubin/INR etc. It can be precipitated by sepsis, dehydration, gastrointestinal bleeding or any condition in which liver function is further impaired (e.g. alcoholic hepatitis, flare of viral hepatitis).

Initial assessment should include:

• Airway, Breathing, Circulation

• Glasgow coma scale

• If GCS <8-10 or evidence of desaturation/risk of aspiration – contact ITU

• Low grade (grade 1-2) vs high grade (grade 3-4) encephalopathy

• Clinical signs of infection, and septic screen including urine dipstick/culture, exclusion of SBP by ascitic tap if ascites present, chest X-ray

• Hydration status

• Severity of liver dysfunction based on laboratory tests

• Drug chart review: all sedating medications should be stopped (see below)

Management:

Empirical hydration therapy, even in the absence of clinical signs of dehydration/hypovolaemia is reasonable, e.g. 1L 0.9% sodium chloride over 4-6 hours then review.

Antibiotics should NOT be prescribed unless there is strong clinical suspicion of infection (refer to antibiotic guidelines on intranet).

Lactulose should be prescribed with the intention of achieving 2 soft stools per day:

15-30mls bd orally, which can be titrated up to 20-30 ml QDS; if the patient is too drowsy or confused to take oral medicine, pass NG tube and give 40ml bolus.

Phosphate enemas are also effective: 1 enema stat then review response in 3-4 hours. If effective prescribe 1-2 enemas daily until sustained improvement in encephalopathy.

Pre-existing medications: potentially sedating drugs such as codeine, tramadol, morphine, and all benzodiazepines should be withheld until conscious level has improved, following which the need for them should be reassessed.

Anti-depressants such as amitriptyline, mirtazapine, venlafaxine and the SSRIs should also be withheld in the short term, and advice should be sought regarding their re-commencement. Withdrawal for more than a few days may cause adverse effects but, in the acute situation with reduced conscious level, it is acceptable to withhold them.

Rifaximin 550mg BD orally can be considered in patients with recurrent HE (1 or more further episode within 6 months of first presentation) despite being on lactulose¹³ and only after discussion with the Hepatology/Gastroenterology team.

Paracetamol

Paracetamol is safe at normal doses in stable cirrhosis. Due to its non-sedating profile, it is a preferred analgesic for mild to moderate pain.

It is important to note that intravenous paracetamol dosage is weight dependent:

In adults with body weight up to 51 kg – 15 mg/kg every 4-6 hours with maximum of 60 mg/kg per day.

In adults with body weight 51 kg and above – 1 g every 4-6 hours with maximum 4 g/day

In decompensated disease (e.g. ascites, variceal bleeding, sepsis, encephalopathy) paracetamol remains safe, although reduced doses are advised (max 3g/day).

Paracetamol becomes unsafe when hepatic stores of glutathione become depleted. This can occur in malnutrition. In underweight or malnourished individuals reduced doses should be prescribed.

Paracetamol is not advised in cases of acute hepatitis i.e. raised transaminase (AST/ALT) levels > 5-10 x upper limit of normal. In all cases of acute hepatitis any prior prescription of paracetamol should be stopped, and it should not be restarted until full recovery in liver function.

Unexplained liver dysfunction or hepatitis in underweight, frail or debilitated patients who use paracetamol regularly (e.g. nursing home resident on 1g qds long term) may in fact represent paracetamol toxicity and consideration should be given to treatment with n-acetylcysteine as per protocol.

Refer to the BASL position statement on paracetamol prescribing for further information¹³.

NSAIDs

Non-steroidal drugs are relatively contraindicated in all forms of liver disease, including stable cirrhosis. They can precipitate renal dysfunction, upper GI bleeding and cause idiosyncratic acute liver dysfunction. Outpatients with very stable disease who take low dose NSAIDs for painful conditions do not need to stop, but the prescription should be reviewed following admission for decompensation or other inter-current illness.

Opiates (codeine, oxycodone, tramadol, morphine, slow-release patches)

The risks and benefits of these potentially sedating and constipating drugs must be assessed on an individual basis. If the patient is drowsy/encephalopathic they should be withheld in the short term, unless a palliative care pathway has been established. Morphine is the preferred opioid in patients with advanced liver disease if an opioid is required.

Other analgesics

Drugs used for chronic/neuropathic-type pain (eg. gabapentin, pregabalin) should be discussed with the pain team on an individual basis.

For more detail regarding prescribing analgesia in end-of-life patients with advanced liver disease please refer to the BASL Symptom Control and End of Life Care in Adults with Advanced Liver Disease guideline