LIVER DISORDERS (PRACTICAL MANAGEMENT) Dr Pok Kern (PK) TAN Gastroenterologist Calvary hospital, ACT 1 st April 2017

Transcription

1 LIVER DISORDERS (PRACTICAL MANAGEMENT) Dr Pok Kern (PK) TAN Gastroenterologist Calvary hospital, ACT 1 st April 2017

2 TOPICS TO COVER Acute liver failure Chronic liver failure Portal hypertension : Ascites Hepatic encephalopathy Alcoholic liver disease NAFLD Not covered Viral Hepatitis HBC/ HCV Autoimmune, Metabolic and vascular diseases

3 ACUTE LIVER FAILURE Defined as INR >1.5 / Prothrombin time increased by 4-6 seconds Altered sensorium Wide differentials Urgent tests Toxicology (Paracetamol) Hepatitis A to E serology (Hep E if visited India, Pakistan, Russia, Mexico) Autoimmune Screen (ANA, Immunoglobulin, Anti Smooth muscle, LKM, Mitochondrial) Metabolic (fulminant Wilson disease)

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5 ACUTE LIVER FAILURE Ischaemic hepatitis Documented hypotension is not always found High Transaminases High LDH : indicative of cell necrosis

6 FULMINANT WILSON S DISEASE High mortality. Young and abrupt onset Coombs negative haemolytic anaemia with high bilirubin Kayser Fleitcher ring in 50% of patients

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8 ACUTE LIVER FAILURE Altered sensorium 2 nd to brain swelling and intracranial HTN Aetiology is unclear Serum ammonia If >220microM predicts increased intracranial pressure Rx Treat underlying aetiology Correct coagulopathy, treat intracranial hypertension, supportive care Orthotopic liver transplant

9 CHRONIC LIVER FAILURE (CIRRHOSIS) Portal hypertension 3 major complications 1. Ascites 2. Varicel bleeds 3. Hepatic encephalopathy

10 CLINICAL SIGNS Shifting dullness? Sensitivity 83% Specificity 56% How much fluid if you find flank dullness on exam? ~ 1500ml Ref: JAMA 1982; 247;

11 PATHOPHYSIOLOGY OF ASCITES Portal hypertension (Pressure > 12mmHg) Splanchnic vasodilation SVR & MAP CO Endogenous vasoconstrictor (Prostacyclin) Water (ADH) and sodium retention(raa) Renal vasoconstrictor (RAA) Ref: Hepatology 1997;26;1149

12 WHAT TO EXPECT IN CIRRHOSIS? Urinary Na retention Increased total body sodium Dilutional hyponatraemia Hyperdynamic circulation Relative hypotension

13 DIURETICS Preferred regime (AASLD 2012) Spironolactone 100mg PO OD PLUS Frusemide 40mg PO OD Benefit : faster fluid mobilisation This ratio maintains normokalaemia Max spironolactone 400mg + frusemide 160mg

14 ?LIMIT TO DAILY WEIGHT LOSS NO if significant peripheral oedema But once the oedema has resolved 0.5 kg/ day is probably reasonable Ref: Rapid diuresis in pt with ascites from CLD; the importance of peripheral oedema ; Gastroenterology 1986;90;

15 ASCITES IN CIRRHOSIS SUMMARY: Na restriction (<2grams/day) and dual diuretic regimen Effective in >90% patient

16 HYPONATRAEMIA IN CIRRHOSIS Common in cirrhotic Pseudohyponatraemia Generally can tolerate well down to ~ 120 Reduce or withhold spironolactonse Fluid restriction (1-1.5L/day) if Sodium continues to drop

17 CHRONIC LIVER FAILURE Hepatic encephalopathy (HE) Manifests with neurological or psychiatric abnormalities 30-40% of cirrhotic Traditionally regarded as fully reversible. Cumulative HE leads to mental deficit Gold standard West Haven criteria Hard to use, interobserver variation

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19 HEPATIC ENCEPHALOPATHY Asterixis + disorientation

20 HEPATIC ENCEPHALOPATHY in cirrhosis ALWAYS have precipitant. Should look for triggers

21 HEPATIC ENCEPHALOPATHY Investigation CT brain Generally do not contribute to diagnosis or grading But 5X increased risk of intracebral bleed so reasonable to do with first HE or suspicious of other aetiology Serum ammonia High level alone do not add diagnostive, prognostic value But if normal, the Dx of HE will be in question

22 HEPATIC ENCEPHALOPATHY Treatment Identify and treat the precipitant. 90% of HE can be treated by just correcting the precipitants Lactulose.Aim for 2-3 loose stools a day. Add rifaximin. need to use with lactulose Haloperidol for agitation Protein restriction NO longer recommended Small meals and hyperalimentation. Late night snack

23 ALCOHOLIC LIVER DISEASE Relationship btw amount consume and risk of cirrhosis is NOT linear RF Drinking outside meal times. 2.7X risk of cirrhosis Binge drinking (5XSD/d for male, 4XSD/female) Female* Overweight Genetic GABA, GABRG3 (not full penetrance) Safe limit <21 SD males /wk <14 SD females /wk

24 ALCOHOLIC LIVER DISEASE Diagnosis History, CAGE questionnaire Clinical features (e.g. parotiditis, Dupytren s contracture, feminisation) Biochemistry (GGT low specificity and sensitivity. More accurate if MCV is also high) Biochemistry Typical pattern AST 2-6X ULN, AST : ALT >2 (70% cases) However AST >500 or ALT >200 Is Uncommon unless concomitant Paracetamol ingestion.

25 ALCOHOLIC LIVER DISEASE Diagnosis (cont) Imaging is to exclude other causes Liver biopsy is NOT necessary Prognostic tool : Maddrey Discriminant function (MDF) To grade severity of alcoholic hepatitis Score >= 32, 30-50% one month mortality

26 ALCOHOLIC LIVER DISEASE Treatment Abstinence improves portal pressure, histology, survival 66% improves significantly after 3/12 Nutritional support Esp breakfast and night time snack Prednisolone if Maddrey Score >32 40mg daily for 4 weeks then taper over 2-4 weeks Pentoxyfyline 400mg TDS for 4 weeks if steroid is contraindicated Oral phosphodiesterase, inhibits TNF and other cytokines

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28 NAFLD Definition Hepatic steatosis on imaging or histology No other causes for 2 nd hepatic fat accumulation e.g. alcohol Subcategorised NAFL simple steatosis. Low risk of progression NASH with inflammation with/without fibrosis Strongly associated with metabolic syndrome

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30 NAFLD Prevalence -up to 90% of pt undergoing bariatric surgery % of type II DM pt on imaging -up to 50% high TG and low HDL -risk increases with age. Most common cause of death is cardiovascular event

31 NAFLD Difficult to differentiate NASH from simple NAFL Important predictor is Metabolic syndrome NAFLD fibrosis score Fibroscan can be used to assess advanced fibrosis

32 NAFLD Treatment To loose weight 5-9% min. Best evidence is Caloric restriction + exercise Significant improvement in steatosis and reversal of histological changes MR spectroscopy ~40% reduction in steatosis kcal energy defect

33 NAFLD Drug therapy What works Pioglitazone improves fibrosis score but limited by Side effects Vitamin E 800IU/day. For non cirrhotic non diabetis NASH What doesn t work (or inadequate data) Metformin Ursodeoxycholic acid Statin (inadequate data) but useful as broader strategy for CVS risk Ezetmibe Omega 3, but can be used to treat hypertriglyceridaemia

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35 NAFLD Bariatric surgery works

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