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 1antitrypsin levels + phenotype 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

• SYMPTOMSNausea & vomiting, diarrhoea, cholestasis, pyrexia,

abdominal pain, jaundice

Fulminant/acute liver failure rare, patient very unwell coagulopathy and encephalopathic

• SIGNSJaundice, 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 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

• 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• Don’t 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 varicesCan Inject gastric varices with glue

Manage in HDU/ITU

Terlipressin IVProphylactic 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 (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

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.