Physical Aspects of Substance Misuse in Older People. Jane Collier Consultant Hepatology John Radcliffe Hospital Oxford

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1 Physical Aspects of Substance Misuse in Older People Jane Collier Consultant Hepatology John Radcliffe Hospital Oxford

2 Areas to cover Hepatitis C Curable disease New drugs (goodbye interferon) Drug Interactions Challenges Screening and getting drug to vulnerable individuals Alcohol related liver disease Complications of cirrhosis Alcoholic hepatitis (jaundice presentation) Non-invasive markers of severe fibrosis/cirrhosis Hepatitis B When to treat

3 Hepatitis C FIND INFECTED INDIVIDUALS AND CURE TREAT IN COMMUNITY

4 Curable 95-98% cure Cure if HCV RNA negative 3 months post treatment 8 to 12 weeks or oral therapy 2-3 drugs Some regimes single tablet /day Well tolerated with few side effects +/- ribavirin Sofosbuvir /Velpatasvir 1 tablet/day 12 weeks Drugs depend on genotype NHSE dictate regime (cheapest) 10-20,000 New drugs pangenotypic so in future may not need genotype CAN RE-INFECT 3 per 100 person/years

5 Effect of DAA treatment on end-stage liver disease Increased number of treatments with introduction of DAAs Falling mortality for hepatitis C cirrhosis Falling numbers listed for liver transplant in US Cirrhosis ; HCC

6 Drug Regimes C E1 E2 NS2 NS3 NS4A NS5A NS5B NS3/4A Protease inhibitor Paritaprevir (ritonovir boosted) Voxilaprevir Grazoprevir Glecaprevir NS5A Polymerase inhibitor Ombitsavir Ledipasvir Velpatasvir Elbasvir Pibrentasvir NS5B Polymerase inhibitor Dasabuvir Sofosbuvir Sofosbuvir Beclabuvir

7 Drug Interactions- Dose adjustments needed Omeprazole Statins Other Drugs Carbamazepine Quetiapine NO NO not all DAAs

8 Ribavirin- will eventually no longer be used Used Older DAA regimes ie ombitasvir containing Decompensated cirrhosis ie previous ascites Better tolerated than when used with interferon 5-6 tablets/day (weight based) 2-3 gram haemoglobin drop Rare side effects Rash Difficulty sleeping/anxiety

9 Hepatitis C Operational Delivery Networks 22 networks set up in July 2015 Initial cirrhotics treated Number of treatment slots/month /network High cost drug- blutec- so NO community pharmacy dispensing ; 10,000 treated/cured across England ; 12,500 treated/cured Thames Valley ODN currently 2 month wait

10 CIRRHOSIS--- can be silent until worsens and get complications ie ascites New kid on the block as a cause of cirrhosis is Non-Alcohol Related Fatty Liver Disease NAFLD/NASH

11 Urgency of treatment- Is my patient cirrhotic Clinical Low platelets ie 140 (N < 150) Splenomegaly on ultrasound (not always practical to get ultrasound) Non-invasive tests (mechanical and serum) Fibroscan > 14.5 cirrhosis > 11.5 suggest moderate scarring < 6 no scarring

12 Non-invasive serum markers of liver fibrosis (no biopsy) Expanded Liver Fibrosis (ELF) Tissue inhibitor of metalloproteinase (TIMP) Procollagen 3 propeptide (PIIIP3) Hyaluronic acid All good negative predictors of scarring FIB-4 Age, platelets, AST, ALT APRI Platelets + AST MED CALC APP

13 Non-Invasive Serum Markers Of Liver Fibrosis Example of How May Help Risk Stratification For Advanced Liver Fibrosis

14 Finding Hepatitis C Cases The new challenge Screening known IVDU users Drug and Alcohol Services GP shared care Finding past users no longer engaged with drug services Finding those previously tested as antibody positive who do not know How to test Hepatitis C antibody point of care capillary sample ( rapid result/ send away) Hepatitis C antigen correlated better with HCV RNA but need venous sample Hepatitis C RNA ( 70% HCV Ab positive) and Hepatitis C genotype need venous sample for confirmatory test ( EDTA sample)

15 Screening intravenous drug users- Oxford TREAT IN COMMUNITY

16 Alcohol

17 Alcoholic Liver Disease- a big problem RISING DEATHS DUE TO ALCOHOL RELATED IVER DISEASE DEATHS INCRESING IN OLDER

18 Natural History Clinical Deterioration Can be sudden Worsening liver scarring Jaundice Unpredictable due to alcoholic hepatitis worsening cirrhosis May get better if stop drinking Cirrhosis often silent

19 Complications of cirrhosis How do you assess prognosis? Worsening Blood Tests Diuretic Resistant Ascites Infected ascites Hepatic Encephalopathy Variceal Bleed alone Alcohol related hepatitis INR/ bilirubin/ creatinine/na 70% mortality at 2 years 50% mortality at 1 year 50% mortality at 1 year 20% mortality 20% mortality ALCOHOL A BIG MODIFIER AS LIVER FUNCTION/SCARRING MAY IMPROVE WITH ABSTINENCE

20 HEPATITIS B UK Universal Vaccination 2017 Intermediate prevalence Eastern Europe 90% of adults with acute hepatitis B will clear

21 Hepatitis B 66 year old man Hepatitis B surface antigen positive Hepatitis B e antigen negative and Hepatitis B e antibody positive screening test had infection a while Hepatitis B DNA 30,000 IU/ml aim < 20,000 ideally < 2,000 Hepatitis Delta antibody negative ALT 40 IU/ml Fibroscan 8.7 Ultrasound- no focal liver lesion, no enlarged spleen coexists with HBV aim < 30 men < 19 women < 6.0 no scarring >10 fibrotic/cirrhotic TREAT Entacavir or Tenofovir

22 Hepatitis B Natural History E antigen +ve Interferon 6 months Entecavir or Tenofovir E antigen - ve Interferon less effective Entecavir or Tenofovir

23 Chronic Hepatitis B Treat (older population) Viral Load > 2-20,000 ALT elevated (ie > 19 women /30 man) High fibroscan Life long Single tablet/day Entecavir or Tenofovir Stop once become HBs Ag negative (can take decades)