Acute and Chronic

Liver Disease
Dr. Orla Crosbie
Consultant Gastroenterologist, CUH

4th Med, 17th Nov 2010

 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
a1antitrypsin levels + phenotype

a-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, a1antitryptin 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, a1 anti-trypsin, male PBCs
Screen cirrhotics with 6 monthly u/sound and
afetoprotein levels
Diagnosis made on imaging (u/s, CT or MRI)
and aFP 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.