Liver disease in 2017: challenges and opportunities

Liver disease in 2017: challenges and opportunities Dr Matthew Cowan Consultant Gastroenterologist and Hepatologist Surrey and Sussex Healthcare NHS Trust Faculty of Physician Associates 2 nd National CPD Conference Tuesday 19 th September 2017

Liver disease in 2017: some rare and esoteric things that I think are interesting (but are totally irrelevant to you) Dr Matthew Cowan Consultant Gastroenterologist and Hepatologist Surrey and Sussex Healthcare NHS Trust Faculty of Physician Associates 2 nd National CPD Conference Tuesday 19 th September 2017

Liver disease in 2017: what is happening now, what is likely to change and how to survive in your job Dr Matthew Cowan Consultant Gastroenterologist and Hepatologist Surrey and Sussex Healthcare NHS Trust Faculty of Physician Associates 2 nd National CPD Conference Tuesday 19 th September 2017

Things to discuss What is happening to liver disease in the UK? What are the most common causes of liver disease? What happens when you acquire a liver disease? What can we do about liver disease? Please interrupt and ask questions

Standardised UK mortality rate data 1970-2011 Williams et al 2014 The Lancet 2014 384, 1953-1997DOI: (10.1016/S0140-6736(14)61838-9)

Figure 2 Standardised liver death rates in countries in the European Union before 2004 (Williams et al 2014) The Lancet 2014 384, 1953-1997DOI: (10.1016/S0140-6736(14)61838-9) Copyright 2014 Elsevier Ltd Terms and Conditions

Alcohol and the liver Patterns of drinking - Mediterranean v Northern European drinking Geographical and societal trends in liver disease in the UK Unit counting and safe limits Slide 10

Number of hospital admissions for NAFLD 1998-2010 (Williams et al 2014) Registrations for liver transplantation in the UK for non-alcoholic fatty liver disease (Williams et al 2014)

Two people with serious liver diseases

Fibrosis progression Generally slow rate of progression of fibrosis in HCV - 1/3 cirrhosis in 20 years - 2/3 cirrhosis in 50 years Alcohol and most other diseases have similar patterns HBV more complex and depends upon stage of chronic infection Coexistent profibrotic conditions are synergistic (eg alcohol, obesity) Identification and treatment can stop and reverse the progression of fibrosis

So how do you tell the difference? Cirrhosis may be obvious - Decompensation - Portal hypertension - Clinical signs (spiders, etc) - Low platelets - Funny scans Or it might not be Liver fibrosis is not obvious Noninvasive markers Blood tests - AST:ALT ratio >1 Fibroscan Biopsy is becoming obsolete for staging liver disease (but is still very helpful for determining cause)

Fibroscan Ultrasound-based test Non-invasive, painless Nurse-delivered clinic Results instantly available Excellent NPV

Child Pugh Score 1 2 3 Encephalopathy None 1-2 (confused) 3-4 (asleep/coma) Ascites None Mild/controlled Moderate Bilirubin <34 34-51 >51 Albumin >35 28-35 <28 INR <1.8 1.1.8-2.3 >2.3 Annualised liverrelated mortality Operative mortality A (5-6) 1-2% 10% - B (7-9) 4-20% 18-45% 81% C (>9) 30-60% 76-82% 100% Post-operative morbidity

What can we do about liver disease? Prevent deterioration in liver function - Minimise alcohol intake - Avoid hepato-toxic drugs - Avoid additional infections Treat the cause of liver disease before significant fibrosis occurs Institute surveillance for HCC and decompensation in cirrhotic patients Manage the complications of liver disease

Interferon-free (and ribavirin-free) regimens for HCV PEARL-1 ABT-450/r + ABT-267 12 weeks oral therapy g1b HCV CLINICAL LIVER Gastroenterology 2014;147:359 365 ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and 100% Sustained Virologic Response With or Without Ribavirin in Treatment-Experienced Patients With HCV Genotype 1b Infection Pietro Andreone, 1 Massimo G. Colombo, 2 Jeffrey V. Enejosa, 3 Iftihar Koksal, 4 Peter Ferenci, 5 Andreas Maieron, 6 Beat Müllhaupt, 7 Yves Horsmans, 8 Ola Weiland, 9 Henk W. Reesink, 10 Lino Rodrigues Jr., 3 Yiran B. Hu, 3 Thomas Podsadecki, 3 and Barry Bernstein 3 1 University of Bologna, Bologna, Italy; 2 Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; 3 AbbVie, Inc, North Chicago, Illinois; 4 Karadeniz Technical University, Trabzon, Turkey; 5 Medical University of Vienna, Internal Medicine III, Vienna, Austria; 6 Elisabeth Hospital, Linz, Austria; 7 University Hospital, Zurich, Switzerland; 8 Université Catholique de Louvain, Brussels, Belgium; 9 Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; 10 Academic Medical Center, Amsterdam, The Netherlands CLINICAL LIVER See Covering the Cover synopsis on page 257. regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725

Longterm suppression of HBV Slide 24

Surveillance in cirrhosis 2-5% risk of decompensation per year Synthetic dysfunction Varices Ascites Encephalopathy 3-7% per year risk of HCC in HCV cirrhosis National recommendations 6/12 afp and U/S Fattovich and Llovet 2006, Ryder 2003

Managing decompensated liver disease Treat portal hypertension - Prevent (or treat) bleeding from varices - Manage ascites - Treat encephalopathy Treat sepsis (including SBP) Optimise nutrition Identify and treat (if possible) hepatocellular carcinoma Once the liver has failed, the only treatment that will reduce the risk of death is liver transplantation

Things to discuss What is happening to liver disease in the UK? - A huge growth industry What are the most common causes of liver disease? - Alcohol (75% of deaths from liver disease) - Obesity - Chronic viral hepatitis What happens when you acquire a liver disease? - A gradual progression of liver fibrosis culminating in cirrhosis What can we do about liver disease? - Plenty as long as we identify it early. Recognising liver disease once patients have cirrhosis is too late Outpatient survival rates 84% one year 66% five years Inpatient survival rates 55% and 31% Half of patients with ALD will die before recovery of liver function

Liver screen Chronic liver disease - Alcohol history - LFT, clotting (FBC, U&E) - HBV sag, HCV Ab* - Autoantibodies, Igs - Ferritin - afp - a1at - Copper / caeruloplasmin if young - Imaging (US first) Acute liver disease - Alcohol history - Drug history - LFT, clotting (FBC, U&E) - Paracetamol levels - HAV, HBV, HEV, CMV, EBV, HIV, (HCV)* - Autoantibodies, Igs - Copper / caeruloplasmin if young - Imaging (US first) *More detailed tests required if positive Slide 29

matthew.cowan@sash.nhs.uk