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Gastro for Psychs 2018.2 [Read-Only] [Compatibility Mode] Gastroenterology/Hepatology An update for the Psychiatrists John Perry North Shore Hospital Auckland, NZ Outline Interpreting liver function tests Common liver conditions Psychotropic medications and the liver Hepatitis C New treatment options and how it affects you Gut stuff Deciphering Liver Tests Pattern recognition!!! What kind of doctor? Deciphering Liver Tests LFTs Other important tests Bilirubin Albumin ALP FBC GGT MCV Platelets ALT PT/INR AST Imaging Liver Function Tests: How to crack the code Bilirubin Isolated rises usually not important Gilbert’s syndrome Haemolysis? Haptoglobins, Combe’s test, Reticulocyte count When raised with other enzymes may suggest significant liver disease Cholestasis Acute hepatitis Drug induced liver injury Liver Function Tests: How to crack the code ALP + GGT Classically “obstructive” enzymes Together rise with intra and extra-hepatic cholestasis, with increased bilirubin ALP alone often from bones GGT alone not usually significant EtOH, Fatty liver, Meds Liver Function Tests: How to crack the code ALT/AST Classically the “Hepatitic” enzymes Most labs only do ALT unless asked Small rises common Fatty liver Infections Viral hepatitis Multiple esoteric causes! High levels = potentially sick Acute hepatitis Paracetamol overdose Drug induced liver injury (DILI) Other important tests Albumin Drops in chronic liver disease (also many other causes) PT/INR Rises in significant liver dysfunction MCV High with alcohol dependence, some meds Platelets Low in alcoholics, low with portal hypertension Hepatitic Bili 28 (<20) ALP 119 GGT 60 (<50) ALT 290 (<45) AST 216 (<45) Albumin 35 N PT/INR 1.1 (0.9-1.1) Platelets 320 N Cholestatic Bili 29 (<20) ALP 560 GGT 492 (<50) ALT 41 (<45) Albumin 35 N PT/INR 1.0 N Platelets 320 N Colestatic LFTS need an ultrasound. Obstruction Liver lesions (cancer?) Mixed pattern Bili 259 (<20) …and pretty sick! ALP 1119 GGT 1303 (<50) ALT 2458 (<45) AST 2621 (<45) Albumin 31 (>34) PT/INR 4 (0.9-1.1) Platelets 490 (150 -390) Some Common Diagnoses Non-alcoholic fatty liver disease (NAFLD) = Fatty liver, sometimes NASH (Gilbert ’s syndrome) Alcoholic liver disease (ALD) Hepatitis B and C Drug-induced liver dysfunction Auto-immune liver diseases (AIH/PBC/PSC) Drug-induced liver injury Many others… NAFLD ALD Hep B Hep C Drug-induced 46 yr old man Others BMI 36 Bili 12 (<20) ALP 110 Minimal alcohol GGT 80 (<50) ALT 57 (<45) Comorbidities: Albumin 38 N Depression PT/INR 1.0 N Hypertension Platelets 276 N Dyslipidaemia Most likely diagnosis? Fatty liver (NAFLD) NAFLD ALD Hep B Hep C Drug-induced 46 yr old Tongan man Others BMI 36 Bili 12 (<20) ALP 110 Minimal alcohol GGT 80 (<50) ALT 57 (<45) Comorbidities: Albumin 38 N Depression PT/INR 1.0 N Hypertension Platelets 276 N Dyslipidaemia Most likely diagnosis? Hepatitis B or Fatty liver NAFLD ALD Hep B Hep C Drug-induced 46 yr old ex-IVDU Others BMI 36 Bili 12 (<20) ALP 110 Minimal alcohol GGT 80 (<50) ALT 57 (<45) Comorbidities: Albumin 38 N Depression PT/INR 1.0 N Hypertension Platelets 276 N Dyslipidaemia Most likely diagnosis? Hepatitis C Pattern Recognition Mild ALT rise = wide differential Clinical context helps In reality, we screen for most things Hep B/C Ferritin Immunoglobulins, auto-antibodies Thyroid function Coeliac screen Alpha-1 antitripsin Ceruloplasmin + serum copper A large patient + negative screen = NAFLD Fatty Liver/NAFLD/NASH NAFLD = non-alcoholic fatty liver disease Fatty liver, no inflammation 30 – 40% of some Western populations! Good prognosis NASH = non -alcoholic steatohepatitis Fatty liver, inflammation, fibrosis/damage occurring About 5% of fatty liver patients May lead to cirrhosis or liver failure, hepatocellular carcinoma Risk factors for progression Hypertension Raised cholesterol Metabolic syndrome Diabetes ALT > 2x ULN Management of NAFLD/NASH Those with risk factors or ALT >100 get referred to clinic Fibroscan is inaccurate Ok if normal, but raised reading may be false positive Losing weight/exercise is the mainstay of therapy So far only bariatric surgery alters outcome Small study showing benefit for rosiglitazone Hepatitis B for the Psychiatrist DNA virus Inserts into your genome 200 Million chronically infected worldwide Vertical transmission mother to child 30 – 90% likely Horizonal infection in children in endemic areas Chronic infection can lead to cirrhosis, liver cancer, death Excellent vaccination available – transmission can be prevented! Consider in Maori, Polynesian, Aborigine, Asian, East European, African Hepatitis B for the Psychiatrist Percentage of chronic HBV infection: < 2% –– Low 22––7%7% –– Intermediate > 8% –– High Margolis et al. 1991 Hepatitis B for the Psychiatrist Important tests: HbSAg (Hep B surface antigen) = infected HbSAb = immune ALT HBV DNA (only request if HbSAg +ve and ALT is raised) The bottom line: HbSAg +ve + raised ALT + HBV DNA>2000 IU/mL = refer for treatment Also refer if evidence of cirrhosis, or family Hx of Hepatoma (HCC) Hepatitis B for the Psychiatrist Treatment of Hepatitis B Suppress the virus with oral medication Entecavir Tenofovir Highly effective Duration of treatment may be many years We’re working on a cure… NAFLD ALD Hep B Hep C Drug-induced 56 yr old man Others Not particularly overweight Bili 26 (<20) Previous alcohol dependence ALP 103 Nil reported now GGT 591 (<50) ALT 53 (<45) Bipolar affective disorder AST 124 (<45) Takes lithium, quetiapine Albumin 32 (>34) Likely diagnosis? PT/INR 1.1 (0.9-1.1) Platelets 102 (150 -390) MCV 106 (81 – 98) Ferritin 1100 (20 – 350) Saturation 39% Alcoholic Liver Disease Alcohol causes a broad spectrum of disease: Fatty liver - Alcoholic hepatitis – Cirrhosis Normal liver Fatty liver Alcoholic Cirrhosis Hepatitis McCullough, AJ, et al. Am J Gastroenterol 1998; 93:2023 Alcoholic Liver Disease Alcohol causes a broad spectrum of disease: Fatty liver - Alcoholic hepatitis – Cirrhosis 90 to 100% Normal liver Fatty liver 10 to 35% 8 to 20% Alcoholic Cirrhosis HCC Hepatitis 40% ? 4% per year McCullough, AJ, et al. Am J Gastroenterol 1998; 93:2023 Alcoholic Liver Disease Management Encourage abstinence/safe drinking Thiamine Refer if significant liver disease Medications Disulfiram (Antabuse) Naltrexone Baclofen Which patients may have cirrhosis? Bili 26 (<20) Look for ALP 103 low albumin GGT 591 (<50) Raised PT/INR ALT 53 (<45) Low platelets AST 124 (<45) Consider: Albumin 32 (>34) Fibroscan PT/INR 1.1 (0.9-1.1) Imaging, usually U/S Platelets 102 (150 -390) Nodular liver MCV 106 (81 – 98) Portal HT Ferritin 1100 (20 – 350) Saturation 39% Refer all cirrhotic patients for assessment Surveillance in cirrhotic patients 2 – 4% annual incidence of Hepatocellular Carcinoma Curable if found early Palliative if not Ultrasound and AFP 6 monthly Improves survival Also screen for varices, 3 yearly What medications are safe with cirrhosis? Severity: Cirrhosis = just scarring. Can have most medications safely! Cirrhosis + Portal Hypertension. Caution but usually ok. Decompensated cirrhosis – beware. Low albumin Raised bilirubin Raised INR Ascites Encephalopathy Risk of precipitating encephalopathy (eg by constipation) Analgesia Paracetamol is the safest analgesic! 3 gm per day limit is safe. Opioids lead to constipation – can be bad. NSAIDs a problem for kidneys and risk of bleeding Methadone safest opiate Transient Elastography (Fibroscan) Transient Elastography (Fibroscan) Ultrasound transducer Mild amplitude, 50 Hz Elastic sheer wave Velocity correlates with stiffness, fibrosis. 5 – 10 mins, starved 3 hrs Transient Elastography (Fibroscan) Result affected by In practice High ALT Liver biopsy avoided in most Ascites Still needed for diagnostic work Obesity Psychotropic medications and the liver Drug Induced Liver Injury: anti-psychotic agents More common with conventional antipsychotic agents: Clorpromazine Less frequently with other phenothiazines Cholestatic hepatitis 2 – 4 weeks after starting Newer agents (atypical) are low risk Some linked with rises in LFTs Clinically apparent liver injury with jaundice exceedingly rare. Clozapine Main risk is agranulocytosis Transient rises in ALT/AST common Usually resolve in 6 – 12 weeks Sometimes require dose reduction Significant liver injury very rare 1 in 2000 patients 30 yr old Maori man. Chronic schizophrenia on clozapine 30 yr old Maori man. Chronic schizophrenia on clozapine Hb 110 Bili 40 WCC 14.9 ALP 86 Neut 11.8 GGT 162 Eos 0.0 AST 4880 Plts 253 ALT 2444 INR 1.8 Na 138 Alb 48 K 3.9 Cr 98 Blood gas: pH 7.406, CRP 105 pO2 8.17 pCO2 5.28 Trop 0.13 HCO3 24 Further investigations No other toxic drugs, no paracetamol Morbidly obese, on CPAP Clozapine level 4370 (toxicity increased if >1000) Echo – dilated cardiomyopathy LFTs trend 6000 5000 4000 U/L 3000 2000 1000 0 AST/ALT trends 20/03/2008 25/04/2008 26/04/2008 27/04/2008 28/04/2008 29/04/2008 29/04/2008 30/04/2008 1/05/2008 2/05/2008 3/05/2008 5/05/2008 date ast 8/05/2008 16/05/2008 alt 19/05/2008 21/05/2008 22/05/2008 6/06/2008 10/06/2008 25/06/2008 3/07/2008 The conclusion? Clozapine-induced cardiomyopathy? Congestive +/- ischaemic hepatitis? Clozapine -induced hepatitis? Clozapine overdose or just decreased hepatic clearance? Most of the above… Other atypical antipsychotics Olanzapine Frequent (10 – 50%) mild rises in ALT, transient Long
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