Chronic Hepatitis

Andrew Bathgate

Chris Bellamy

Royal Infirmary of Edinburgh

Case

• 60 years, male

• Follicular NHL 1988

• Multiple previous lines of treatmentCHOP X 6 1999Relapse with high grade transformation RIVE X 3 September 2006BEAM autograft May 2007Relapse R-DHAPP X 3 May 2013End of treatment PET showed no evidence of residual disease

• BM allograft planned August 2014

Sept 13 Oct 13 Jan 14 Apr 14

ALT 18 58 162 204

ALK PHOS 106 134 141 168

BILIRUBIN 6 13 13 12

• Bone Marrow Transplant unit assessment Aug 14

• Hepatitis E IgM and RNA positive

• Stored serum tested HEV RNA negative July 2013

• Liver biopsy Sept 2014 - ? chronic HEV/fibrosis

Follow-up

• Ribavirin 400mg BD started Oct. 2014, ALT 631

• Nov. 2014, ALT 19, HEV PCR negative.

• Stopped Ribavirin Nov. 2014, norovirus.

• Dec. 2014, ALT 18, low level PCR HEV positive

• Given Ribavirin 200mg bd, taken 9 days

• March 2015, ALT 16, PCR negative.

• Allogenic peripheral blood stem cell transplant transplant April 2015

• Gut CMV reactivation

• GVHD skin and gut, on Pred 25mg

• Jan 2016, ALT 85, HEV PCR positive, ribavirinrestarted 400mg bd

• HEV sequencing = same virus

Chronic hepatitis E

• Solid organ transplantation

• Haematological malignancy Tamura2007, Tavitian2010

• stem cell transplantation Peron2006

• including reactivation LeCoutre2009

• Other immunosuppression• Pauci-immune vasculitis

• SLE on treatment Grewal2014

• Rarer• HIV with low CD4 count Dalton2009, Kaba2011

• CD4 T cell defect HonerZuSiederdissen2014

• apparently immunocompetent individuals

Chronic HEV management

Case- March 2016

• 54 year old man presents with jaundice

• Type 1 diabetes mellitus

• Abnormal liver enzymes 2012/14- presumed drug-induced liver injury by statins

• General lassitude but no other symptoms

• Recent trip to Bulgaria

• Tadalafil switched to daily from PRN 4 months previously

• Tamsolusin -2 years

Nov 10 Mar 12 Sep 14 Dec 14 Mar 16 Apr 16

BILI 20 17 13 21 50 58

ALT 71 126 25 143 465 531

Alk Phos 65 66 68 69 267 248

Hepatitis A-E negativeFerritin 448Immunoglobulin G 60g/l (uln 15)Smooth muscle ab negativeMitochondrial ab negativeANA 1/640 homogenous patternDs DNA ab 36 IU (uln 20)

Liver biopsy arranged

April 16 Commenced 9mg budesonide daily

May 16 bili 29, ALT 229, ALP 173

commenced azathioprine

June 16 bili 18, ALT 46, ALP 87

IgG 30

Mar 17 bili 21, ALT 18, ALP 48

budesonide 3mg, azathioprine 75 mg

Autoimmune Hepatitis- Introduction

• Annual incidence 1.9/100 000 in Northern European population

• Prevalence 16.9/100 000

• Around 5% of all liver transplants

• Female preponderance (4:1)

• All ages and ethnic groups susceptible

• Type 2 (LKM1 positive) more common in Europe

Scoring system

Treatment

• Oral prednisolone 40-60 mg (budesonidealternative), tapering of dose as ALT improves

• Azathioprine 50-150 mg depending on weight and response

• Rapid response (no symptoms, ALT < 2 x ULN, normalising of IgG) decrease disease progression

• About 50% develop cirrhosis although prognosis still good (10% mortality in 15 years)

Case- May 2013

• 58 year old Pakistani manHBsAg positive – resp clinic

Recent peritoneal TB

Ischaemic heart disease- coronary stents

Drugs- candesartan, aspirin, esomeprazole

finishing off anti-TB therapy

• HBeAg negative, HBeAb positive

Bili 9, ALT 24, ALP 84

HBV genotype D

HBV DNA 12,000 IU

hylauronic acid 17ng/ml (minimal fibrosis)

April 14 Sept 14 March 15

Bilirubin 5 5 8

ALT 69 30 61

ALP 84 66 85

HBV DNA 21,143 6,431 26,809

Fluctuating ALT, HBV DNA consistently over 2000 ? Inflammation/fibrosisBMI 30

Follow-up

• No indication for oral anti-viral

• Oct 15- ALT 22, HBV DNA 14,472

• June 16- ALT 25, HBV DNA 36,000

Dec 16- CABG

Regular review- HCC surveillance 6 monthly

Chronic Hepatitis B

• Becoming more common in UK due to immigration

• ALT and HBV DNA reasonable markers of active disease

Stages of chronic infection

The indications for treatment are generally the same for both HBeAg-positive and HBeAg-negative CHB.

This is based mainly on the combination of three criteria:

Serum HBV DNA levels > 2000 IU/l and serum aminotransferase levels > ULN for local lab value

Histology: moderate/severe hepatitis and/or F2 METAVIR

EASL Guidelines

2016 HBV algorithm

HCV algorithm