1. Acute and Chronic Liver Disease
Dr. Orla Crosbie
Consultant Gastroenterologist, CUH
4th Med, 17th Nov 2010

2. Contents
Investigations
Acute Liver disease
Chronic Liver Disease

3. 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

4. Liver function tests 1 Bilirubin – Conjugated and Unconjugated
ALT/AST levels
Alkaline Phosphatase
gGT
Albumin
INR
FBC

5. 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)

6. 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.

7. MRCP

8. ERCP

10. 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

11. Jaundice Pre hepatic Hepatic – any liver disease, acute or chronic
Haemolysis
Conjugation abnormalities
Hepatic – any liver disease, acute or chronic
Post hepatic – Obstruction

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

13. Acute Liver Disease Infections Drugs – MANY – HERBALS/OTC Alcohol
Viral Hepatitis A, B, C, D, E, EBV, CMV, HSV,
Others – Leptospirosis, Toxoplasma,
Drugs – MANY – HERBALS/OTC
Alcohol
Poisons
Vascular obstruction (eg. Budd Chiari)

14. Acute Liver Disease SYMPTOMS SIGNS
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

15. 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*

16. 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

18. 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

19. Chronic Liver Disease - symptoms
None
Fatigue
Malnutrition
Ascites, ankle oedema, pleural effusions – weight gain
Impotence
Bleeding
Jaundice, itch, steatorrhoea

20. 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….

21. 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

22. 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.

25. 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

26. 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

27. 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

28. Chronic Liver Disease - Decompensation
Ascites + renal failure
GI bleeding
Encephalopathy
Jaundice
Hepatocellular carcinoma

31. 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
Don’t fluid restrict

33. 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

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

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

36. 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

38. 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)

39. 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

40. 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

43. 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.

44. 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
ascites
Uncontrolled variceal haemorrhage
Encephalopathy
Hepatoma – Milan criteria
Disease specific criteria: Rising Bilirubin in PBC
Need to consider Q of Life and Other illnesses

45. 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…

46. 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.