The Impact of Curing HCV on the Liver and the Extra ...s3.gi.org/meetings/mn2016/16ACG_Hep_School_Midwest_0013.pdf · IVer Bon Secours Health System The Impact of Curing HCV on the

Mitchell L. Shiffman, MD, FACG

Liver Institute of VirginiaEducation, Research and Treatment for Patients with Liver Disease

IVerBon SecoursHealth System

The Impact of Curing HCV on the Liver and the Extra-Hepatic Manifestations of

Chronic HCV

Mitchell L. Shiffman, MD, FACGDirector

Liver Institute of VirginiaBon Secours Health System

Richmond and Newport News, VA, USA

IVer

CURING HCVTHE VIRUS, THE LIVER, THE PATIENT

• We can now “cure” HCV in almost all patients

• However, we may not cure organ damage from HCV

Liver fibrosis

Cirrhosis

Extra-hepatic injury

• Until these “scars” resolve, our patients remain at risk

HCC

Mortality

Reduced quality of life

ACG 2016 Midwest Hepatitis School Copyright 2016 American College of Gastroenterology

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AN SVR MAY NOT CURE THE LIVERPERSISTENT ELEVATION IN ALT

• Elevated ALT in patients with SVR:

2-8% of patients treated with PEG-IFN

1% of patients treated with oral anti-viral therapy

• What causes this?

IFN-induced immune hepatitis

Another co-existent liver disease

NAFLD

Alcohol consumption

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CURING HCVPERSISTENT ELEVATION IN HCV

AT is a 67-year-old male who was found to have chronic HCV, GT1B with HCV RNA of 1.2 million IU in 1/2015. AST and ALT were 86/97 with normal ALP, TBILI, albumin, and a platelet count of 195K. A laboratory assessment of fibrosis was 0.5 and shear wave elastography 7.1 kPa. He was treated with the combination of “paritaprevir-ritonavir-ombitasvir- dasabuvir” for 12 weeks and achieved SVR.

He is referred back to you because of elevated liver enzymes; AST and ALT of 55/69. The ALP, TBILI, and albumin remain normal and platelet count is 185K. HCV RNA is undetectable. A liver ultrasound shows increased echogenicity.


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ELEVATION IN ALT AFTER SVRAPPROACH

• Since liver biopsy is now rarely performed, co-existent liver disorders may be missed

• Monitor patients and serum ALT for at least a few years after SVR

• Serologies for other causes of liver disease if ALT is persistently or intermittently elevated

• Ultrasound to screen for fatty liver/chronic liver injury

• Consider liver biopsy to define etiology

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AN SVR MAY NOT CURE THE LIVERASSESSMENT BY FIBROSURE

T Poynard et al.J Hepatol. 2013; 59:675-683.

Patients with SVRN=171Fibrosis Regression

Patients with SVRN=171Fibrosis Progression


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PATIENTS WITH SVRMAY DEVELOP CIRRHOSIS

T Poynard et al.J Hepatol. 2013; 59:675-683.

Why do 12% of patients progress to cirrhosis?• They actually had cirrhosis

before treatment• Interferon stimulation of the

immune response. • Will not be seen with oral

anti-viral agents• Co-existent NAFLD• ETOH• Other unrecognized liver

disorders

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SVR MAY NOT CURE THE LIVERPERSISTANCE OF LIVER INJURY

0

2

4

6

8

10

Infla

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atio

n S

core

0

1

2

3

4

5

Fib

rosi

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core

Baseline

5 Years

ML Shiffman et al.Ann Hepatol 2014; 13: 340–349.


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SVR MAY NOT CURE THE LIVERPERSISTENCE OF FIBROSIS

ML Shiffman et al.Ann Hepatol 2014; 13: 340–349.

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SVR MAY NOT CURE THE LIVERTHE POINT OF NO RETURN

• N=120 patients• Advanced cirrhosis• Treated 12 weeks• SOF+SMV• Overall SVR = 81%• Patients with MELD

>20 did not appear to improve

• HCC developed in some patients that appeared to improve

SMVSOF

LT

HCC

Adapted from ML Shiffman et al.Am J Gastroenterol 2015; 110:1179-1185.


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SVR MAY NOT CURE THE PATIENTPERSISTANCE OF MORTALITY RISK

AJ van der Meer et al.JAMA 2012; 308:2584-2593.

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SVR MAY NOT CURE THE LIVERPERSISTANCE OF HCC RISK

AJ van der Meer et al.JAMA 2012; 308:2584-2593.


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CURING HCVPERSISTENCE OF HCC RISK

MM is a 65-year-old male who was found to have cirrhosis and chronic HCV, GT2 in 2006. Liver function was normal and he had no prior hepatic decompensation. He was treated with PEG-IFN and RBV for 24 weeks and achieved SVR. He was followed for 2 years by the gastroenterologist and then referred back to his PCP.

In 11/2015 he develops severe RUQ pain and is found to have an 8 cm liver left-lobe mass by ultrasound. A dynamic MRI shows the mass has typical features of HCC and there is invasion of the left portal vein.

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ASSESSING THE LIVER AFTER SVRAPPROACH

• Shear wave elastography or laboratory assessments of fibrosis annually until fibrosis is resolving.

• In patients with cirrhosis:

Ultrasound every 6 months to screen for HCC

Until:

• All liver function studies and platelets are normal?

• Shear wave elastography or laboratory assessment of fibrosis no longer suggests advanced fibrosis?


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SVR MAY NOT CURE THE PATIENTPERSISTANCE OF NON-LIVER INJURY

• Although cryoglobulinemia resolves in patients with SVR organs which have been injured by cryoglobulinsdo not appear to recover CKD secondary to MPGN Neuropathy Neurocognitive changes

• B cell lymphoma• Diabetes mellitus• Fatigue• Quality of life

L Alric, et al. Am J Kidney Dis 2004; 43: 617–623.A Ammendola, et al. Muscle Nerve 2005; 31: 382–385.

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CURING HCVRESOLUTION OF CRYOGLOBULINEMIA

CW is a 54-year-old female who developed ulcerations on her toes, severe toe pain such that she could not stand or walk. She was found to have HCV, GT1A. Liver enzymes, function and platelets were normal. A shear wave elastographywas 4.5 kPa. Rheumatoid factor and cryoglobulins were positive. She was treated with “ledipasvir-sofosbuvir” for 8 weeks and achieved SVR. 1 month into treatment the foot pain was gone. All toe lesions resolved within 8 weeks.


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CURING HCVPERSISTENCE OF ORGAN DAMAGE

JF is a 57-year-old male with chronic HCV GT1B, HTN and DM. A liver biopsy in 2010 demonstrated stage 1 fibrosis. He failed treatment with PEGIFN/RBV in 2010. He returns for evaluation in 1/2015 because of abdominal and lower-extremity swelling and is found to have obvious ascites and 3+ lower edema. Serum creatinine is now 2.5 mg. Urine analysis 4+ protein. 24 hr urine collection 4 grams of protein. Rheumatoid factor positive. Cryoglobulins negative. He is treated with “grazoprevir-elbasvir” for 12 weeks and achieves SVR. Ascites resolves, proteinuria resolves but serum creatinine remains in the 2.5-3.0 range.

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PREVENTING HCV RELATED DISEASEIMPACT OF SVR/TREATMENT

Y Kawamura et al. Am J Med 2007; 120: 1034–1041.Y Arase et al. Hepatology 2009; 49: 739–744.YC Hsu et al. Hepatology 2014; 59: 1293–302.

TreatmentNo Treatment

IN PTS WITH DM


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CURING HCV IMPACT ON LIVER DISEASE

• Curing HCV leads to fibrosis regression and in some cases resolution of cirrhosis.

• However,

Liver injury may not resolve if there is another co-existent cause of liver disease.

Liver cancer risk persists in patients with cirrhosis

• All patients must be properly assessed for evidence of liver disease before and after the patient has been cured of HCV.

• Ensure that the liver disease has in fact resolved

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CURING HCV IMPACT ON EXTRA-HEPATIC DISEASE

• Curing HCV causes resolution of cryoglobulinemaand other immune manifestations of HCV

• All features of cryoglobulinemia resolve

• However,

End-organ damage from the effects of cryoglobulinema may not resolve.

• All the more reason to treat HCV before it damages the liver and extra-hepatic sites


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The Impact of Curing HCV on the Liver and the Extra ...s3.gi.org/meetings/mn2016/16ACG_Hep_School_Midwest_0013.pdf · IVer Bon Secours Health System The Impact of Curing HCV on the