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,
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Carbohydrate metabolism
Lipid metabolism
Bile acid metabolism
Bilirubin metabolism
Hormone inactivation
Drug inactivation and excretion
Immunological function
Liver function tests 1
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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,
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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
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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
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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 Maddrey’s 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
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Ascites + renal failure
GI bleeding
Encephalopathy
Jaundice
Hepatocellular carcinoma
Ascites
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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
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Low salt diet
Diuretics: Spironolactone and Frusemide
Therapeutic large volume paracentesis – albumin replacement
Shunts – TIPS
Transplantation
• DAILY WEIGHTS, WATCH U&Es
• Don’t fluid restrict
Spontaneous Bacterial
Peritonitis
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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 (King’s criteria)
– Paracetamol Overdose: pH, INR, creatinine and Encephalopathy
– Non-paracetamol: INR, Bilirubin, age, cause, encephalopathy
• Chronic Liver Disease: Mainly for Decompensation
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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
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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.