1-Acute_Liver_Disease-6y.presentation pptx

Acute liver diseases presentation

1. Acute Liver Disease Prepared by: Dr. Ruqaya Al- Kathiry

2. PRESENTING PROBLEMS IN LIVER DISEASE Liver injury may be either acute or chronic. Presentation of Liver Disease Chronic Liver Injury ( hepatic injury, inflam . ± fibrosis for >6ms) Acute Liver Injury Severity In early stages: asymptomatic with fluctuating ABNL LFTs. ABNL LFTs + non specific symptoms of fatigue Mild/moderate Signs of cirrhosis ± portal HT Jaundice Severe Chronic liver failure (May not occur until several years after cirrhosis has presented) Jaundice Ascites Hepatic encephalopathy (HE) Portal HT with variceal bleeding Acute liver failure Very severe

3. INFECTIONS AND THE LIVER These include hepatotropic viral infections, bacterial & protozoal infections. Each has specific C/Fs & requires targeted Rx. Viral Hepatitis This must be considered in anyone presenting with ↑ transaminases (AST, ALT). Causes of viral hepatitis Common ( majority of hepatitis virus infections) • Hepatitis A • Hepatitis B ± hepatitis D • Hepatitis C • Hepatitis E Less common ( ABNL LFTs in most pts. & occ. J occurs) • CMV • EBV Rare • HSV ( rare cause of hepatitis in adults, mostly immunocompromised) • Yellow fever Non-A, non-B, non-C (NANBNC) or non-A-E hepatitis is used to describe hepatitis due to a virus that is not HAV, HBV, HCV or HEV. ABNL LFTs are also common in chickenpox, measles, rubella & ac. HIV infection. These viruses cause similar C/Fs & pathological features which are anicteric or even asymptomatic. They differ in their tendency to cause ac. & chr. infections.

4. C/Fs: Hx: Symptoms rarely last >3-6 wks. Non-specific prodromal illness: H, myalgia , arthralgia, N, A & distaste for cigarettes usu. precedes J by a few ds to 2wks. V & D may follow, & abd . discomfort is common. Dark urine & pale stools may precede J . O/E: There are usu. few physical signs. Tender liver but only minimally enlarged. Mild splenomegaly & cervical LAP more in children or those with EBV infection. Invx: S. transaminases (AST, ALT): 200-2,000U/L in ac. infection ( ↓ & fluctuating in chr. infec ) Plasma bilirubin: reflects the degree of liver damage. ALP: rarely >2x upper limit of NL. PT: NL. Prolongation indicates the severity of the hepatitis but rarely >25s, except in rare cases of ac. liver failure. WBC: NL with a relative lymphocytosis . Serological tests: confirm the aetiology of the infection.

5. Management: Most do not need hospital care. Drugs which are metabolised in the liver (sedatives & narcotics) should be avoided. No specific dietary modifications are needed. Alcohol should be avoided during ac. illness. Elective surgery should be avoided in ac. viral hepatitis, as there is a risk of post-op. liver failure. Liver Tx is very rarely indicated for ac. viral hepatitis complicated by liver failure. Complications of Acute Viral Hepatitis ( rare ) • Acute liver failure • Cholestatic hepatitis (hepatitis A) • AA • CLD & cirrhosis (hepatitis B & C) • Relapsing hepatitis

6. Acute Liver Failure (Fulminant Hepatic Failure) It is an uncommon but serious condition. Definition: “Progressive deterioration in liver function & mental changes progressing from confusion to coma occurring within 8wks of onset of the precipitating illness, in the absence of evidence of preexisting liver disease .” This distinguishes it from cases in which HE represents a deterioration in CLD. Liver failure occurs when there is insufficient metabolic & synthetic function for the needs of the pt. The direct cause is usu. ac. loss of functional hepatocytes : In a pt with NL liver: very high injury is needed to cause liver failure (FHF). In a pt with CLD: the ac. insult is much less to ppt. liver failure. Although liver biopsy may be necessary, it is the presence or absence of the C/Fs suggesting chronicity that guides the clinician. Classification of acute liver failure Common causes Cerebral oedema Time: J to encephalopathy Type Viral, paracetamol Common < 7 days Hyperacute Cryptogenic, drugs Common 8-28 days Acute Cryptogenic, drugs Uncommon 29 days-12 weeks Subacute

7. Pathophysiology: Any severe cause of liver damage can produce ac. liver failure. Acute viral hepatitis is the most common cause worldwide. Paracetamol toxicity is the most frequent cause in UK.

8. Clinical Assessment: Cerebral disturbance (HE ± cerebral oedema) is the cardinal manifestation of ac. liver failure, but in the early stages this can be mild & episodic. Its absence does not exclude a significant ac. liver injury. HE: ↓alertness & poor conc. → restless & aggressive → drowsiness → coma. Cerebral Oedema: ↑ICP → unequal or ABNL reacting pupils, fixed pupils, HT, ↓P.R, ↑R.R, profuse sweating, local or general myoclonus , focal fits or decerebrate posturing. Papilloedema occurs rarely & is a late sign. General Symptoms: Weakness N & V RHC discomfort occ. J: may not be present ( e.g. paracetamol overdose) or even rare (Reye’s syndrome). Death may occur before J develops. Fetor hepaticus (??) can be present. Liver: NL size but later becomes smaller. Hepatomegaly is unusual &, in the presence of a sudden onset of ascites, suggests venous outflow obst. as Budd- Chiari syndrome. Splenomegaly is uncommon & never prominent. Ascites & oedema are late developments & may be a consequence of I.V.F.

9. Invx: To determine the cause of the liver failure & prognosis. • Toxicology screen: of blood & urine • HBsAg (may be -ve), IgM anti- HBc (best screening test for ac. hepatitis B infection) • IgM anti-HAV • Anti-HEV, HCV, CMV, HSV, EBV • Caeruloplasmin , S. Cu, urinary Cu, slit-lamp eye examination • Autoantibodies: ANA, ASMA, LKM, SLA • Immunoglobulins • U/S: of liver & Doppler: of hepatic veins PT: rapidly becomes prolonged; this is the lab. test of greatest prognostic value & should be carried out twice/d; to avoid using FFP except in frank bleeding. Factor V levels: can be used instead of PT to assess degree of liver impairment. Plasma bilirubin: degree of J. Plasma aminotransferase : is particularly ↑ (100-500xNL) after paracetamol overdose, but ↓ as liver damage progresses & is not helpful in determining prognosis. Plasma albumin: NL unless the course is prolonged. Percutaneous liver biopsy: C/I because of the severe coagulopathy , but biopsy can be undertaken using the transjugular route if appropriate. Management: Pts with ac. liver failure should be Rx in a high-dependency or ICU.

10. Monitoring in Acute Liver Failure Cardiorespiratory • P.R • B.P • CVP • R.R Neurological • Intracranial pressure monitoring • Conscious level Fluid balance • Hourly output (urine, V, D) • Input: oral, I.V Blood analyses • ABG • CBC • S. electrolytes: Na, K, HCO3−, Ca, Mg • RFT: Creatinine, urea • Glucose (2-hourly in acute phase ) • PT Infection surveillance • Cultures: blood, urine, throat, sputum, cannula sites • CXR • Temperature Complications of Acute Liver Failure • Encephalopathy and cerebral oedema • Hypoglycaemia • Metabolic acidosis • Infection (bacterial, fungal) • Renal failure • MOF (hypotension and respiratory failure)

11. Adverse Prognostic Criteria in Acute Liver Failure: • H⁺ >50 nmol /L (pH <7.3) at or beyond 24 hrs following the overdose Or • S.creatinine > 300μmol/L ( ≅ 3.38mg/dL ) + PT > 100s + encephalopath y G 3/4 Non-paracetamol cases • PT > 100s Or • Any 3 of the following: J to encephalopathy time > 7d Age <10 or >40 yrs Indeterminate or drug-induced causes Bilirubin >300 μ mol/L (≅17.6 mg/dL) PT >50secs Or • Factor V level <15% & encephalopathy grade 3 or 4 N.B: It predicts a MR of ≥90% and are an indication for referral for possible liver Tx . Conservative Rx to maintain life in the hope that hepatic regeneration will occur, but early transfer to a specialised transplant unit should always be considered. N- acetylcysteine may improve pts with ac. liver failure due to paracetamol poisoning. Liver Tx is an imp. Rx option for ac. liver failure. 1-yr SR following liver Tx for ac. liver failure is ~60% can be expected.

12. DRUGS AND THE LIVER The liver is the 1ary site of drug metabolism & an imp. target for drug-induced injury. Pre-existing liver dis. may affect metabolism of drugs & toxicity may occur when given drugs in NL doses. These can exacerbate known complications of cirrhosis. N.B: An unDx liver disease should always be considered in pts exhibiting unexpected effects following drug exposure.

13. Drug-induced Liver Injury: Drug toxicity should always be in the D/D of pts presenting with ac. liver failure, J or ABNL liver biochemistry. The most common picture is a mixed cholestatic hepatitis. Presence of J indicates more severe liver damage. Although ac. liver failure occurs, most drug reactions are self-limiting & chr. liver damage is rare. ABNL LFTs often take wks following a drug-induced hepatitis & ms following a cholestatic hepatitis → NL . Permanent bile duct loss ( ductopenia ) may follow a cholestatic drug reaction → chr . cholestasis → itching . Dx of ac. drug-induced liver dis : take a detailed drug Hx (keep in mind that liver injury can take wks or ms to develop following exposure).

14. A liver biopsy should be considered if there is suspicion of pre-existing liver dis. or if blood tests fail to improve when the suspect drug is withdrawn. Where drug-induced liver injury is suspected or cannot be excluded, the drug should be discontinued unless it is impossible to do so safely.

15. Types Of Liver Injury: Different histological patterns of liver injury may occur with drug injury. Pure Cholestasis : Selective interference with bile flow in the absence of liver injury can occur with: Oestrogens which was common when >50μg/d were used as OCPs. Both the current OCP & HRT can be safely used in CLD. Chlorpromazine Cholestatic Hepatitis: ABX: flucloxacillin & co- amoxiclav is the most common ABX to cause ABNL LFTs but, unlike others, it may not produce symptoms until 10-42d after it is stopped. Anabolic steroids used by body-builders. NSAIDs & COX-2 inhibitors: there is overlap with ac. hepatocellular injury. Acute Hepatocyte Necrosis: Paracetamol ( most common ): Ac. hepatocellular necrosis with ↑ S.transaminases ,. Diclofenac & INH: Inflam . is not always present but accompanies necrosis. Allopurinol : Granulomas may be seen. Herbal remedies. Recreational drugs (cocaine). Steatosis: Microvesicular hepatocyte fat deposition: tetracyclines & Na valproate. Macrovesicular hepatocyte fat deposition: tamoxifen & amiodarone toxicity → similar histological picture to NASH.

16. Vascular/Sinusoidal: Alkylating agents used in oncology → damage the vascular endothelium → hepatic venous outflow obst. Chr. overdose of vit . A → damage the sinusoids → local fibrosis → portal HT. Hepatic Fibrosis: Most drugs cause reversible liver injury & hepatic fibrosis is very uncommon. MTX: * when started → ac . liver injury * in ↑ doses over a long time → cirrhosis . RFs for drug-induced hepatic fibrosis: pre-existing liver dis. & ↑ alcohol intake.

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