/Hepatology An update for the Psychiatrists

John Perry North Shore Hospital Auckland, NZ Outline

¢ Interpreting 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

¢

¢ Encephalopathy

¢ Risk of precipitating encephalopathy (eg by )

¢ 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 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

AST/ALT trends

6000

5000

4000

3000 U/L

2000

1000

0

8 8 8 8 8 8 8 8 08 08 08 08 08 08 00 20 /200 /200 20 200 20 /2008 /200 200 20 /2008 20 20 4 4 4/ 4/ 5 5/2 5 5/ 5/ 6 0 0 0 /04/200 0 /0 /0 0 /05/200 0 5/ 6/ 8/ 9 1/0 2 3/05/2008 5/05/2008 8 6/ 9 6/0 3/07/2008 20/03/ 2 2 27/04/ 2 2 29/04/200830/ 1 1 21/05/200822/ 10/06/ 25/06/ date

ast alt 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 gradual rise associated with weight gain = NAFLD

¢ Rare instances of more significant abnormalities – cholestatic or hepatitic

¢ All resolve with cessation, no progressive damage

¢ Quitiapine

¢ Frequent (30%) transient abnormalities

¢ Rare significant injury (jaundice 1 – 4 weeks after starting, hepatitic LFT picture), cases of liver failure reported

¢ Cross-reactivity with risperidone

¢ Risperidone

¢ Frequent (30%) early transient rises in LFTs

¢ Early reversible injury (ALT and ALP rise)

¢ Rare late mixed or cholestatic injury months or years later Anti-depressants

¢ MAO inhibitors

¢ Early versions very hepatotoxic

¢ More recent ones ok, though risk of late hepatitis 1 – 3 months into treatment

¢ Tricyclic anti-depressants

¢ Transient rises in ALT/AST

¢ Rare instances of significant liver injury

¢ Varies according to type

¢ SSRIs

¢ 10% incidence of transient rises in ALT/AST

¢ Rare clinically significant injury Anti-depressants

¢ Citalopram + Escitalopram

¢ LFT abnormalities <1%

¢ Rare liver injury with jaundice, fatigue, and

¢ Resolves on stopping

¢ Venlafaxine

¢ LFT abnormalities <1%

¢ Rare liver injury 1 – 3 months into treatment

¢ Resolves on stopping Mood stabilisers – Valproate

¢ Transient rises in ALT common, resolve

¢ 3 distinct serious presentations: st ¢ 1 : Hyperamonaemia with minimal/no evidence of liver injury

¢ Confusion then possibly coma

¢ High serum ammonia

¢ Improves 1- 2 days after stopping valproate nd ¢ 2 : Acute hepatocellular injury + jaundice

¢ 1 – 6 months after starting

¢ Hepatocellular or mixed pattern

¢ Multiple reported cases of liver failure/fatalities

¢ IM carnitine may be beneficial if given early rd ¢ 3 : Reye-like syndrome – children

¢ Lethargy, confusion, high ALT but not bilirubin

¢ Raised amonia Drug-induced liver injury (DILI)

¢ Minor rises in ALT/AST common, resolve

¢ Cholestasis usually means discontinue med, may be slow to resolve

¢ Jaundice + DILI-induced hepatitis (ALT/AST) = bad!

¢ Panic and call for help How to be a Hepatologist livertox.nih.gov

Hepatitis C Virus

¢ RNA virus

¢ Identified in 1987

¢ Slowly progressive liver disease ¢ Significant morbidity in most patients ¢ Chronic fatigue, brain fog ¢ Increase in all-cause mortality

¢ Cirrhosis/Liver failure/Death in 20 – 30% Prevalence downunder

¢ Australia – 270 000 cases, 1.28% prevalence

¢ Dropping fast!

¢ NZ - No compulsory reporting, unknown exact numbers

¢ Estimated 50 000 New Zealanders infected

¢ Less than half diagnosed

¢ 10% have accessed treatment, 5% have been cured HCV Genotypes in NZ

G 3 G 1

G 2 The Evolution of HCV Treatment

+ + Pegylated- Interferon Ribavirin Interferon Ribavirin Interferon:

MISERY IMMUNOMODULATION SUFFERING

PSYCHIATRIC ILLNESS

DEATH The Evolution of HCV Treatment

+ + + Direct Acting Antivirals IFN RV PEG-INF RV Rapid improvement in Genotype 1 The Evolution of HCV Treatment

Peg- Interferon+R Interferon- + + + ibavirin free + Direct acting Regimes! Pegylated- Ribavirin antiviral Interferon Ribavirin Interferon Graveyard of Past Therapies

Leaches Frontal Lobotomy

Interferon for HCV

Pangenotypic drugs are here

¢ Epclusa (Velpatasvir + Sofosbuvir)

¢ Aus - better

¢ Maviret (Grecaprevir + pibrentasvir)

¢ NZ - cheaper

¢ Once a day treatment, 8 or 12 weeks

¢ Genotype doesn’t matter

¢ No expected side-effects

¢ Few drug interactions

¢ Quetiapine needs dose reduction for Maviret

¢ 98-99% cure rates WHO Target: Pangenotypic DAAs with increased diagnosis Ù prevalence declines by 80%, deaths, HCC & cirrhosis by 85% by 2030

Total Infected Cases (Viremic) — New Zealand Liver Related Deaths — New Zealand 450 60,000 400 50,000 350 40,000 300 250 30,000 200 20,000 150 10,000 100 50 - -

Baseline IFN DAAs G1 only DAAs all Genotypes Baseline IFN DAAs G1 only DAAs all Genotypes

HCC — New Zealand Decompensated Cirrhosis — New Zealand 400 900 800 300 700 600 500 200 400 300 100 200 100 - -

Baseline IFN DAAs G1 only DAAs all Genotypes Baseline IFN DAAs G1 only DAAs all Genotypes Treatment Uptake – Reducing Treatment Uptake • Numbers per month (total period July 2016-Sept 2017) We could run out of patients to treat!

Most easy-to-reach patients have now been cured How you can help

¢ Do HCV testing in your clinics

¢ Any history of illicit drug use

¢ Test once with routine bloods

¢ Encourage HCV positive patients to get cured

¢ GP, Liver Clinic

¢ Consider treating in-patients

¢ Call for advice After HCV is cured

¢ Patients can still be re-infected

¢ No immunisation achieved

¢ Advise on harm reduction

¢ There is no reactivation later

¢ HCV Ab test remains positive - ignore

¢ HCV RNA test is negative (indicating cured)

¢ Cirrhotic patients should improve

¢ Unless other risks for progression

¢ Alcoholism, obesity

¢ Important: Cirrhotic patients can still get Hepatocellular Carcinoma

¢ Need ongoing surveillance with U/S + AFP Gut stuff for the Psychiatrist …

¢ Gastroesophageal Reflux

¢ Constipation Gastroesophageal Reflux (GORD)

¢ Physiological reflux occurs postprandially, not at night

¢ GORD = reflux causing troublesome symptoms and/or complications

¢ Very common

¢ 10 -20% of patients in West, <5% in Asia

¢ Symptoms:

¢ and regurgitation

¢ Water brash, , chest pain, chronic cough, nausea

¢ Dysphagia – alarm symptom

¢ Diagnosis

¢ On symptoms alone if classical Endoscopy pictures

¢ Management ¢ Risk factors

¢ Modify risk factors ¢ Obesity ¢ Avoid late meals ¢ Alcohol ¢ Elevate the bed? ¢ Caffeine ¢ Antacids

¢ Acid suppression ¢ Smoking

¢ Ranitidine ¢ Chocolate

¢ PPIs ¢ Hiatus ¢ Promotility agents (domperidone)

¢ Endoscopy if alarm symptoms or new reflux >45 years old

¢ Surgery if failure of medical therapy Barrett’s Oesophagus

¢ Change due to chronic reflux

¢ Risk of progression

¢ Dysplasia to adenocarcinoma

¢ <1% in lifetime

¢ Surveillance every 3 years usually Are PPIs safe to take long term?

Probable concerns: Not proven:

¢ Rebound hyper-acidity ¢ B12 deficiency

¢ So wean gradually ¢ Osteoporosis

¢ Increased GI infections ¢ Pneumonia ¢ C. difficile ¢ Dementia

¢ Low Mg levels Very rarely:

¢ Interstitial nephritis

¢ Mircroscopic colitits (lansoprazole) Constipation – what’s new?

¢ Divided into two types

¢ Slow transit

¢ Obstructed

¢ Do cause a lazy bowel? Management of slow transit

¢ Basic advice

¢ Fibre, H 2O, exercise

¢ Laxatives

¢ Osmotic

¢ Stimulant

¢ Rectal preparations

¢ Specialist review

¢ Transit study

¢ Prucalopride 2mg daily Forest plot of randomised controlled trials of laxatives versus placebo in chronic idiopathic constipation.

Ford A C , and Suares N C Gut 2011;60:209-218

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved. “Psychotropic Bowel”

¢ Anticholinergics

¢ Clozapine

¢ Anticholinergic

¢ Seratonergic ¢ Studied colonic transit times in 14 patients

¢ Clozapine treatment

¢ Clozapine + protocol

¢ Laxatives increased colonic transit time in most patients

¢ Subjective constipation symptoms didn’t improve

¢ Protocol was nothing fancy:

¢ Coloxyl + Senna 2 nocte, then 2 bd

¢ PR to exclude impaction

¢ Magracol

¢ 1 sachet bd Long-term concerns with laxative use?

¢ No.

¢ There is no convincing evidence of structural or functional impairment of enteric nerves or intestinal smooth muscle.

¢ Safe to use both osmotic and stimulant laxatives

¢ Causing “lazy bowel” is a disproven myth

Wald A, J Clin Gastroenterol 2003;36(5):386 Psychiatric patients can get bowel cancer too

¢ Bowel cancer is very common ¢ 1 in 11 patients will get it in their lifetime

¢ Consider referral for investigation if: ¢ Persistent new symptoms not obviously due to med changes ¢ Alarm symptoms ¢ Weight loss, recurrent bleeding, progressive pain ¢ FHx ¢ Bleeding (dark red = always refer), outlet type usually ok ¢ Anaemia ¢ +ve iFOBs Thank you

¢ Any questions?

Faecal Mycrobiota Transplantion Faecal Mycrobiota Transplantation

¢ “The administration of faecal material containing distal gut microbiota from a healthy individual donor to a patient with a disease or condition related to dysbiosis, or alteration of their ‘normal ’ gut microbiota”

¢ The gut has evolved with us!

¢ Historically th ¢ 4 Century China th ¢ Veterinary medicine since 17 Century

¢ Psuedomembranous colitis 1958 The problem:

¢ C. difficile

¢ Usually post antibiotic use

¢ Treated with metronidazole then vancomycin

¢ Significant recurrence rate, sometimes multiple

¢ New hypervirulent strain 0127

¢ North America, Europe

¢ High 30 day mortality in compromised patients

¢ High morbidity in recurrent disease

¢ Huge disease burden

N Engl J Med 2015; 372:825-34, Lancet 2005; 366: 1079-84 Before FMT for recurrent C. dif

¢ Tapered long vancomycin course

¢ Pulsed therapy?

¢ Saccharomyces boulardii and other probiotics

¢ (Rifaxamin) FMT: What is involved?

¢ Donor screening

¢ Free of transmissible infection

¢ No intrinsic GI illness

¢ No auto-immune disease

¢ No history of chronic pain syndromes

¢ No evidence of metabolic syndrome

¢ No history of malignancy FMT: What is involved? Efficacy in recurrent C. difficile

Mechanism of successful treatment

Gastroenterology 2015 What about FMT for other diseases?

Inflammatory Bowel Disease

¢ Mixed results, uncontrolled case series

¢ Two recent RCTs:

¢ 75 patients with Ulcerative Colitis 6wks FMT vs water Remission 24% vs 5% with placebo

¢ 50 patients with Ulcerative Colitits FMT once, then repeated 3 weeks later vs autologous (via naso-duodenal tube) No significant difference (but high dropout rate)

Gastroenterology 2015 March, April What about FMT for other diseases?

Obesity

¢ Effective in ex-germ-free mouse model

¢ Pilot RCT in human

¢ FMT from lean to obese individuals

¢ Improved insulin sensitivity and increased gut microbial diversity

Gastroenterology 2012; 143:913 -6 What about FMT for other diseases?

¢ Irritable bowel syndrome?

¢ No reliable evidence yet

¢ Under investigation:

¢ Type 2 Diabetes

¢ Fatty liver disease

¢ Multidrug resistant organism eradication

¢ Hepatic encephalopathy

¢ Paediatric allergy disorders Safety of FMT: Short Term

¢ Minor immediate symptoms common

¢ Abdominal discomfort, , , diarrhoea, constipation, borborygmy, , transient fevers.

¢ Serious AE’s are rare

¢ Colonoscopic complications

¢ Transfer of enteric pathogens

¢ Aspiration risk (NG)

¢ Safe in immunocompromised patients Long-Term Safety/Implications

¢ Pathogens

¢ Currently unidentified

¢ New pathogens

¢ Conditions associated with gut microbiota

¢ Obesity ¢ Non-alcoholic fatty liver

¢ Diabetes disease

¢ Atherosclerosis ¢ Irritable bowel syndrome

¢ IBD ¢ Asthma

¢ Colon cancer ¢ Autism? Availability of FMT

¢ Australia, New Zealand, China, Europe

¢ No restrictions

¢ Canada

¢ ‘New Biological Drug ’

¢ USA

¢ Under FDA restrictions

¢ Patient perceptions?

¢ DIY in the community?

The future of FMT

¢ Registered donors?

¢ Stool banks

¢ Commercial products:

¢ Full spectrum stool-based products

¢ Defined microbial consortia Faecal Mycrobiota Transplant

¢ Key Points:

¢ Highly-effective for recurrent C. difficile

¢ Evolving data on potential benefit and/or harm in other GI and non-GI conditions

¢ Theoretical long-term safety concerns

¢ Use with caution and informed consent