Key facts:
Authors: Natalie Acors and Andrew Stein
Top tip: Why are you not giving steroids? They improve mortality
Key Differential Diagnoses
- Infection
- Hepato-renal syndrome
- Other causes liver dysfunction
Key Investigations
- FBC, ESR, CRP
- U+E, LFT/GGT, Bone, Glucose
- INR
- ECG, CXR
- Liver/abdominal US
Key Treatment
- PREDNISOLONE 40 mg od
- IV PABRINEX 2 vials tds 3-6d, then THIAMINE 100 mg tds, for 1 mth
Key Management Decision
- Steroids
Background
The word 'hepatitis' is a misnomer; as transaminases (AST/ALT) rarely exceed 200, and never exceed 400 U/L
Introduction
- This syndrome has only relatively recently been described. The pathogenesis is not completely understood
- It is important as severe cases have a high mortality (15-50% at 30d)
- 40% are dead at 1 year
- The diagnosis is often missed - and it is treatable.
- Many patients have cirrhosis at presentation (this may be first presentation of cirrhosis)
- Sepsis or bleeding are common precipitants, often spontaneous bacterial peritonitis
Definition
- Progressive inflammatory liver injury associated with long-term heavy intake of ethanol
Terminology
- Try to avoid phrases like 'alcoholic' and 'alcoholism'; they are judgemental
- Do you drink 'too much'? What is 'too much?. It is better to talk about alcohol dependence syndrome; or 'this patient has a high alcohol consumption'
Epidemiology
- More common in non-Caucasians
Risk factors
- Alcohol
Symptoms
- Asymptomatic
- Or, non-specifically (nausea, vomiting, anorexia and diarrhoea)
- Fever (exclude infection)
- Occasionally RUQ pain
Key Questions
- "When did your symptoms start?"
- "How much alcohol do you drink (now and previously)?"
Signs
- Jaundice
- Enlarged tender hepatomegaly
- Ascites, encephalopathy
- Of liver failure/fluid overload
Investigation
Blood
- FBC (Hb falling rapidly ?bleeding ?haemolysis; low platelets, ?portal hypertension/hypersplenism; anaemia and low platelets suggests cirrhosis)
- ± Blood film (if low platelets)
- ± Reticulocytes (haemolysis may occur as part of Zieve’s syndrome)
- ESR/CRP, INR
- U+E (Na low, ?hepato-renal syndrome (HRS); whatever cause, carries poor prognosis)
Note: HRS is rare, only occurs in patients with severe liver disease, and once established is usually fatal. Early recognition and treatment imperative - LFT/GGT: [Ref]
Note: transaminases not that elevated; usually <200; always <400; AST>ALT (vs other hepatic diseases); if v high (>10,000) think of paracetamol OD or ischaemia - Bone, Glucose (may be low)
- BC
- ABG, if unwell (and platelets OK)
Other
- ECG
- CXR (fluid overload, sepsis)
- Liver/abdominal US with Dopplers (large and bright or features of cirrhosis and portal hypertension; also to exclude HCC, portal vein thrombosis as cause of deterioration)
Key Investigations
- Liver/abdo US
- Ascitic tap if ascites (spontaneous bacterial peritonitis, SBP?)
Ascitic tap
Biochemistry
- Protein
- Transudate has a total protein < 30 g/L - eg, cirrhosis, heart failure, nephrotic syndrome
- Exudate has a total protein > 30 g/L - eg, carcinomatosis, infection, TB
- Glucose: in SBP and neoplasm, decreased glucose (<3.0 mmol/L); due to increased glucose consumption
- Lactate dehydrogenase (LDH): increases significantly (>500 iu/L) in SBP (and neoplasm)
- Amylase: in pancreatitis (or perforated viscus) the amylase may be 5x the serum level
Cytology
- Should only be performed when neoplasm is suspected
Bacteriology
- WC, gram stain and culture
- The diagnosis of SBP is suggested by a polymorphonuclear (PMN) cell count in excess of 250 cells per cubic millimetre; in the absence of evidence of an alternative source of infection (secondary peritonitis), such as viscus perforation or intraabdominal abscess
- When mononuclear cells predominated, tuberculosis or fungal infection is likely
- Gram stain may help to differentiate the organism in ascitic fluid infection. It is more frequently positive in secondary peritonitis
- Dont forget to put some fluid in a BC bottle
Specialist Investigations
Blood
- 'Hepatic screen' (Immunoglobulins, anti-mitochondrial AB, anti-smooth muscle AB; ANA/dsDNA; ferritin (may be increased in any acute illness, but iron studies and transferrin saturation may clarify), caeruloplasmin (if <45years); αFP; Anti-HA IgM, HBsAg, Anti-HCV,)
- ± EBV, CMV
- ± Tumour markers (CA 125, CA 15-3, CA19-9, CEA, AFP)
- ± Haptoglobin/LDH (haemolysis)
Other
- Liver biopsy (Transjugular biopsy may be required)
Differential Diagnoses
- Infection; 10% will have sepsis even in the absence of clinical signs; fever may be a reflection of SIRS
- Hepato-renal syndrome
- Consider alternative causes of liver dysfunction (viral hepatitis, haemochromatosis) or acute liver insult on background of alcoholic liver disease (paracetamol OD, ischaemia)
Treatment
Treatment
Drugs
- IV PABRINEX 2 vials tds, for 3-6d; give over 30 mins (resus equipment to hand); before changing to oral treatment (PO THIAMINE 100 mg tds, for one month)
- ± IV GLUCOSE, 20 mls 50%, if BG <4 mmol/L
Note: GLUCOSE increases risk of Wernicke's encephalopathy, so give IV PABRINEX first - ± IV CO-AMOXICLAV 1.2 g tds (to cover Spontaneous Bacterial Peritonitis (SBP))
- ± PO CHLORDIAZEPOXIDE 20-40 mg qds, gradually reducing over 7-14d (Rx DTs/agitation); prescribe PRN doses as well; many clinicians start at dosages that are too low
- ± Rx of seizures
- Avoid sedatives if encephalopathy present
- Avoid nephrotoxic drugs and diuretics
Procedures
- IV
- Daily weights
- High calorie, low salt, high protein diet
- Monitor LFT, U+E, INR
- Fluid restrict if Na <125
- Diagnostic ascitic tap (WC > 250 neutrophils indicates SBP)
Prescribing issues
- Significant risk of anaphylaxis with PABRINEX
Key Management Decision
- Prednisolone/not
[Ref]
Stop
- Alcohol
Treatment
(second line)
Drugs
- PREDNISOLONE 40 mg od for 5/7, then tapered over 28d. There is some evidence that a subset of patients with severe alcoholic hepatitis benefit from prednisolone. But all patients with GI bleeding, sepsis or renal impairment were excluded from the trials
Note: prednisolone should not be started if there is any suspicion of sepsis (10% will have sepsis even in the absence of clinical signs. Full sepsis screen must be completed before prednisolone considered - If suspected variceal bleeding, give IV TERLIPRESSIN 2 mg stat, then 1-2 mg qds (provided no active cardiac ischaemia); for upto 72h
- Give 4.5% HAS if renal impairment is present. If no response, IV TERLIPRESSIN 0.5 mg qds
Procedures
- If unwell, urinary catheter, CVP line, arterial line (if clotting/platelets OK)
- Endoscopy
Admit?
- Usually
Bed plan
- Medical admission ward
- ± Gastroenterology
- ± ITU
Referrals
Medical
- Hepatology
- ± ITU
Other
- Dietitian
- Community alcohol service
The Rest
Complications
- Cirrhosis
- Variceal haemorrhage
- Sepsis (including SBP)
- Hepato-renal syndrome
Follow-up
- Hepatology/gastroenterology
- Community alcohol service
Prognosis
- 30-day mortality = 15% (severe liver disease 50%)
- If no encephalopathy, jaundice, or coagulopathy, 30-day mortality < 5%
- 1-year mortality rate after hospitalization for AAH = 40%
Note: worse if female, older, WC increased, or abnormal clotting; long-term prognosis depends heavily on whether patients have established cirrhosis and whether they continue to drink
Risk stratification
(who can be managed as outpatient)
- If patient well with no melaena, ascites or encephalopathy, and bilirubin <100, they can be managed as outpatient
2° Prevention
+ Health promotion
- Encourage attendance at community alcohol service, and Alcoholics Anonymous
- To most patients, advise NO aclohol consumption for 6 months, in first instance
- If no end-organ damage, then normal 'safe' alcohol limit is advised (<4 units a day for male, <3 for female). If end-organ damage, patient should remain teetotal
- ACAMPROSATE – helps relieve intense anxiety, cravings and insomnia
- DISULFIRAM – causes unpleasant side effects with alcohol ingestion
'Safe' alcohol consumption
Don't forget
- To consider prednisolone
- SBP .. ie, if in doubt, give antibiotics as well
- Community alcohol service referral at discharge
Red flags
- Reduced conscious level
- GI Bleeding
- Hyponatraemia or renal impairment
- Continued drinking
