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 2nd National CPD Conference

Tuesday 19th 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





Liver disease in 2017: what is

happening now, what is likely

to change and how to survive

in your job

Dr Matthew Cowan





Liver disease in 2017:

challenges and opportunities

Dr Matthew Cowan





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…

The Lancet 2014 384, 1953-1997DOI: (10.1016/S0140-6736(14)61838-9)

Williams et al 2014

Standardised UK mortality rate data

1970-2011

Things to discuss






Figure 2

The Lancet 2014 384, 1953-1997DOI: (10.1016/S0140-6736(14)61838-9)

Copyright © 2014 Elsevier Ltd Terms and Conditions

Standardised liver death rates in

countries in the European Union

before 2004 (Williams et al 2014)

http://www.elsevier.com/termsandconditions

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

Registrations for liver transplantation in the

UK for non-alcoholic fatty liver disease

(Williams et al 2014)

Number of hospital admissions

for NAFLD 1998-2010 (Williams

et al 2014)

Things to discuss






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 liver-

related mortality

Operative

mortality

Post-operative

morbidity

A (5-6) 1-2% 10% -

B (7-9) 4-20% 18-45% 81%

C (>9) 30-60% 76-82% 100%

Things to discuss






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

ABT-450, Ritonavir, Ombitasvir, and Dasabuvir Achieves 97% and100% Sustained Virologic Response With or Without Ribavirin inTreatment-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 andBarry Bernstein3

1University of Bologna, Bologna, Italy; 2Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; 3AbbVie, Inc, NorthChicago, Illinois; 4Karadeniz Technical University, Trabzon, Turkey; 5Medical University of Vienna, Internal Medicine III, Vienna,Austria; 6Elisabeth Hospital, Linz, Austria; 7University Hospital, Zurich, Switzerland; 8Université Catholique de Louvain,Brussels, Belgium; 9Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; 10Academic MedicalCenter, Amsterdam, The Netherlands

See Covering the Cover synopsis on page 257.

BACKGROUND & AIMS: The interferon-free regimen of ABT-

450 (a protease inhibitor), r itonavir, ombitasvir (an NS5A

inhibitor ), dasabuvir (a non-nucleoside polymerase inhibi-

tor), and ribavir in has shown efficacy in patients with

hepati t is C virus (HCV) genotype 1b infection—the most

prevalent subgenotype worldwide. We evaluated whether

r ibavir in is necessary for ABT-450, r itonavir, ombitasvir,

and dasabuvir to produce high rates of sustained virologic

response (SVR) in these patients. METHODS: We performed

a multicenter, open-label, phase 3 tr ial of 179 patients with

HCV genotype 1b infection, without cirrhosis, previously

treated with peginterferon and ribavir in. Patients were

assigned randomly (1:1) to groups given ABT-450, r itonavir ,

ombitasvir , and dasabuvir, with r ibavir in (group 1) or

without (group 2) for 12 weeks. The pr imary end point was

SVR 12 weeks after treatment (SVR12). We assessed

the noninfer ior ity of this regimen to the rate of response

reported (64%) for a similar population treated with

telaprevir, peginterferon, and ribavir in. RESULTS: Groups

1 and 2 each had high rates of SVR12, which were non-

infer ior to the repor ted rate of response to the combination

of telaprevir, peginterferon, and r ibavir in (group 1: 96.6%;

95% confidence interval, 92.8%–100%; and group 2: 100%;

95% confidence interval, 95.9%–100%). The rate of

response in group 2 was noninfer ior to that of group 1. No

virologic failure occurred during the study. Two patients

(1.1%) discontinued the study owing to adverse events,

both in group 1. The most common adverse events in groups

1 and 2 were fatigue (31.9% vs 15.8%) and headache

(24.2% vs 23.2%), respectively. Decreases in hemoglobin

level to less than the lower limit of normal were more

frequent in group 1 (42.0% vs 5.5% in group 2; P < .001),

although only 2 pat ients had hemoglobin levels less than 10

g/ dL. CONCLUSIONS: The interferon-free regimen of ABT-

450, r itonavir , ombitasvir , and dasabuvir , with or without

r ibavir in, produces a high rate of SVR12 in treatment-

experienced patients with HCV genotype 1b infect ion. Both

regimens are well tolerated, as shown by the low rate of

discontinuations and generally mild adverse events.

ClinicalTrials.gov number: NCT01674725

Keywords: PEARL-II; Ribavirin-Free; IFN; Interferon-Free

Therapy.

Watch this article’s video abstract and others at http://tiny.cc/j026c .

Scan the quick response (QR) code to the leftwith your mobile device to watch this article’svideo abstract and others. Don’t have a QR codereader? Get one by searching ‘QR Scanner ’ inyour mobile device’s app store.

Untreated chronic hepatitis Cvirus (HCV) infection is

a leading cause of liver damage, cirrhosis, and he-

patocellular carcinoma.1 The prevalence of HCV infection is

estimated to be 3% worldwide and results in approximately

350, 000 deaths annually.2,3 Genotype 1 accounts for ap-

proximately 70% of all HCV infections and subgenotype 1b is

most predominant in Europe and Eastern Asia. Approved

direct-acting antiviral agents (DAAs), telaprevir, boceprevir,

sofosbuvir, and simeprevir, given with peginterferon

(pegIFN) and ribavirin (RBV), have reported sustained viro-

logic response (SVR) rates of 67%–89% in HCV genotype

1–infected patients. Response rates with DAA regimens are

generally lower in patients who have failed previous pegIFN-

containing treatment regimens than in treatment-naive

Abbreviations used in this paper: AE, adverse event; ALT, alanineaminotransferase; AST, aspartate aminotransferase; CI, confidence in-terval; DAA, direct-act ing antiviral agent; HCV, hepatitis C virus; pegIFN,peginterferon; RBV, ribavirin; RT-PCR, reverse-transcrip tion polymerasechain reaction; SVR, sustained virologic response; SVR12, sustainedvirologic response 12 weeks after treatment; TEAE, treatment-emergentadverse event; ULN, upper limit of normal.

© 2014 by the AGA Institute0016-5085/

http://dx.doi.org/10.1053/j.gastro.2014.04.045

Gastroenterology 2014;147:359–365

CLI

NIC

AL

LIV

ER

Open access under CC BY-NC-ND license.

Longterm suppression of HBV

Slide 24

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

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


- A huge growth industry


- Alcohol (75% of deaths from liver disease)

- Obesity

- Chronic viral hepatitis


- A gradual progression of liver fibrosis culminating in cirrhosis


- 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

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liver disease in 2017: challenges and opportunities

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