Acute and Chronic

Liver Disease

Contents
Investigations
Acute Liver disease
Chronic Liver Disease

Normal Liver Function

Protein synthesis and degradation:
albumin, transport proteins, clotting factors,

Carbohydrate metabolism
Lipid metabolism
Bile acid metabolism
Bilirubin metabolism
Hormone inactivation
Drug inactivation and excretion
Immunological function

Liver function tests 1

Bilirubin Conjugated and Unconjugated

ALT/AST levels
Alkaline Phosphatase
gGT
Albumin
INR

FBC

Liver function tests 2

Hepatitis antibodies: A, B, C.D, E
EBV, Toxo, CMV, Leptospirosis

Ferritin and fasting transferrin saturation,

Haemochromatosis genetics

Caeruloplasmin and copper (serum),

24 hour urine for copper

Autoantibodies: ANA, ASMA, AMA, Coeliac

Immunoglobulins: IgG, IgA, IgM
Cholesterol, triglycerides, glucose, TFTs
antitrypsin levels + phenotype
1
fetoprotein (cirrhotics only)

Imaging
Ultrasound Liver substance, lesions, gallbladder
and biliary tree, vessels (Doppler exam), spleen
size and varices
CT scan confirm small lesions, see pancreas
MRI of Liver classify smaller lesions
MRCP: Magnetic resonance
cholangiopancreatography, to see the biliary tree
ERCP: Endoscopic retrograde
cholangiopancreatography diagnostic and
therapeutic: stones, strictures etc.

MRCP

ERCP

Liver Biopsy
Very useful for confirming a diagnosis,
staging degree of inflammation and/or
fibrosis, iron content, mass lesions
Contraindications: Bleeding disorders,
ascites, small liver, uncooperative patient
Complications: Bleeding, pain, perforation
another viscus, biliary leak, pneumothorax
Methods: Percutaneous, transjugular,
laparoscopically

Jaundice
Pre hepatic
Haemolysis
Conjugation abnormalities

Hepatic any liver disease, acute or

chronic
Post hepatic Obstruction

Gilberts syndrome
Deficient glucuronyl transferase
Unconjugated hyperbilirubinaemia, other
LFTs normal
2-5% population
Jaundice when dehydrated
Low grade haemolysis
Normal liver, life expectancy etc.

Acute Liver Disease

Infections
Viral Hepatitis A, B, C, D, E, EBV, CMV, HSV,
Others Leptospirosis, Toxoplasma,

Drugs MANY HERBALS/OTC

Alcohol
Poisons
Vascular obstruction (eg. Budd Chiari)

Acute Liver Disease

SYMPTOMS
Nausea & vomiting, diarrhoea, cholestasis, pyrexia,
abdominal pain, jaundice
Fulminant/acute liver failure rare, patient very unwell
coagulopathy and encephalopathic

SIGNS
Jaundice, hepatomegaly, abdominal tenderness +
splenomegaly, flap/foetar

Acute Liver Disease: treatment

Supportive mainly
Remove precipitating cause if known eg. drugs
Treat some cases eg. Leptospirosis, some viral
infections in acute phase,
Expect complications and treat as they arise eg:
Infection
Bleeding

Outcome
Resolve
Worsen and develop FLF (? Transplant)
Progress to chronic liver disease, may require specific therapy*

Paracetamol toxicity
Present in many preparations***
10gms (20 tablets) can cause fatal liver failure
Initial N&V often settles with symptoms of liver
failure developing 2-3 days later
Coagulopathy and raised ALT
Paracetamol levels may be low/neg by this stage
High index of suspicion
Treat if in any doubt with N-acetylcysteine

Chronic Liver Disease

Alcohol
Autoimmune autoimmmune hepatitis, PBC (Primary
Biliary cirrhosis), PSC (Primary Sclerosing Cholangitis)
Haemochromatosis
Chronic Viral hepatitis: B & C
Non-alcoholic fatty liver disease (NAFLD)
Drugs (MTX, amiodarone)
Cystic fibrosis, 1antitryptin deficiency, Wilsons disease,
Vascular problems (Portal hypertension + liver disease)
Cryptogenic
Others: sarcoidosis, amyloid, schistosomiasis

Chronic Liver Disease - symptoms

None
Fatigue
Malnutrition
Ascites, ankle oedema, pleural effusions
weight gain
Impotence
Bleeding
Jaundice, itch, steatorrhoea

Alcohol
Fatty liver may have no symptoms
Alcoholic Hepatitis can be unwell with liver
and renal failure, jaundice, coagulopathy
Cirrhosis and its complications

Can present at any stage above

ACCURATE ALCOHOL HISTORY
Clues: LFTS: gGT, MCV
Other problems: medical (pancreatitis,
malnutrition, infections, cardiac), social.

Tx. Of Alcoholic Hepatitis

Feed (Enterally)
Vitamin replacement: Thiamine: IV Pabrinex and
multivitamins
Treat DTs
Corticosteroids if Maddreys discriminant function
higher than 32:
50% mortality rate
mDF= 4.6 x (PT patient-control) + Bilirubin/17.1 umol/L

Treat with steroids: Prednisolone 40mg X1/12

Other scoring systems: Glasgow Alcoholic Hepatitis
Score, MELD score

Fatty Liver
Many Secondary causes of fatty liver, including drugs,
alcohol, previous surgery
Primary fatty liver or non-alcoholic fatty liver disease
(NAFLD) commonly recognised now
Some patients in addition to fat on liver biopsy can have
inflammation as well (steatohepatitis) and are referred to
as NASH (non- alcoholic steatohepatitis), a portion of
these will develop scarring and can progress to cirrhosis
over time
Is associated with obesity, non-insulin dependent
diabetes, dyslipidaemia and hypertension; considered
part of syndrome X/metabolic syndrome
Fatty liver getting more common obesity increasing.

Hereditary haemochromatosis
Commonest genetic problem N. European
Progressive iron overload leading to liver
disease (cirrhosis and hepatocellular
carcinoma), diabetes, pigmentation,
arthropathy, hypogonadism, cardiac.
Not always symptomatic at diagnosis

Hereditary haemochromatosis
Need high serum ferritin level and fasting
transferrin saturations to make diagnosis
Fasting Transferrin Saturation > 45%
Raised Serum Ferritin > 350ug/L
Genetics: C282Y and H63D mutation
REMEMBER: MANY CAUSES OF RAISED
FERRITIN

Hereditary haemochromatosis
If HH confirmed
LFTs and ultrasound +/- Liver biopsy to
diagnose Cirrhosis
Prognosis worse if diabetic or cirrhotic at time of
diagnosis
If cirrhotic, need tumour surveillance
Treatment is phlebotomy to render iron deficient
and prevent organ damage, does not remove
risk of HCC
Life long

Chronic Liver Disease Decompensation

Ascites + renal failure

GI bleeding
Encephalopathy
Jaundice
Hepatocellular carcinoma

Ascites

Associated with a poor prognosis

Often associated with ankle oedema, pleural effusions
Diagnostic paracentesis: 1. Biochemistry, 2. Micro & 3. Cytology
SAAG: Serum albumin/ascites gradient > 11g/dl
Risk of Spontaneous Bacterial Peritonitis

Therapy

Low salt diet

Diuretics: Spironolactone and Frusemide
Therapeutic large volume paracentesis albumin replacement
Shunts TIPS
Transplantation

DAILY WEIGHTS, WATCH U&Es

Dont fluid restrict

Spontaneous Bacterial
Peritonitis

Risk: Ascites and Chronic liver disease

Often vague symptoms
Diagnosis: Diagnostic paracentesis for
WCC > 250 cells/mm3 and mainly polymorphs
Culture
Usually Gram negatives
Treat antibiotics +/- albumin
Antibiotic prophylaxis

Variceal bleeding
Due to portal hypertension
Varices at porto-systemic anastomoses
Skin Caput medusa
Oesophageal & Gastric
Rectal
Posterior abdominal wall
Stomal

Medical emergency

Resuscitate patient
Good IV access
Cross-match blood
and clotting factors
Emergency OGD

Band oesophageal varices

Can Inject gastric varices with
glue
Manage in HDU/ITU
Terlipressin IV
Prophylactic antibiotics
U/sound and doppler portal vein
Rebleed: Rescope,
Balloon tamponade,
May need TIPPs shunt, transplant

Prevention of variceal
haemorrhage
PRIMARY PREVENTION: Have not bled
Scope all cirrhotics
If large varices: B block with Propranolol or
Band varices.

SECONDARY PREVENTION: After bleed

Repeat banding until varices eradicated +/propranolol (ideally measure portal pressures)

Encephalopathy
Confusion due to liver disease
Graded 1-4
Precipitants: GI bleed, infection, constipation,
dehydration, medication esp. sedation
Flap asterixis and hepatic foetar
Treat underlying cause,
Laxatives phosphate enemas and lactulose
Rifaximin-broad non absorbed spectrum
antibiotic

Hepatorenal syndrome
Progressive renal failure in the setting of
advanced liver disease and portal
hypertension
Rule out other causes for renal failure:
Pre-renal, Microscopy, ultrasound
Type 1 (acute) and Type 2 (chronic)
Very poor prognosis

Hepatocellular Carcinoma
(Hepatoma)
Primary Liver Cancer
Usually in setting of cirrhosis
Risk factors: Viral hepatitis B/C, Alcohol,
haemochromatosis, 1 anti-trypsin, male PBCs
Screen cirrhotics with 6 monthly u/sound and
fetoprotein levels
Diagnosis made on imaging (u/s, CT or MRI) and
FP levels in cirrhotics biopsy usually not done
Cure: transplant or surgery
Palliation: TACE, radiofrequency ablation, Sorafenib
po.

Liver transplantation
INDICATIONS:
Fulminant Liver failure determined by certain clinical
criteria (Kings criteria)
Paracetamol Overdose: pH, INR, creatinine and Encephalopathy
Non-paracetamol: INR, Bilirubin, age, cause, encephalopathy

Chronic Liver Disease: Mainly for Decompensation

ascites
Uncontrolled variceal haemorrhage
Encephalopathy
Hepatoma Milan criteria

Disease specific criteria: Rising Bilirubin in PBC

Need to consider Q of Life and Other illnesses

Liver transplantation
WAITING LIST: MELD scoring system
Liver Matched by blood group and size
Post operative
Immunosuppression to prevent rejection eg.
Tacrolimus, Mycophenolate and Steroids
Prophylaxis against infection eg. CMV, HSV, PCP
Can get graft failure, vascular thrombosis, rejection
(acute and chronic), infections, disease recurrence

Liver disease: summary

LFTs
Causes of jaundice
Causes of acute hepatitis
Causes of cirrhosis Risk factors
Symptoms and Signs of liver disease
Ascites, encephalopathy & SBP, variceal
haemorrhage, HCC and hepatorenal
syndrome.