Huda Alquraishi Rashid hospital Dubai - UAEs-Presentation.pdf · Huda Alquraishi Rashid hospital...

Update in Viral hepatitis

Huda AlquraishiRashid hospital

Dubai

Huda Al Quraishi

Agenda

• Introduction

• Case presentation

• Guidelines

• Conclusion

Introduction

• Retreating HCV is crucial

• In the era of highly effective DAAs, 1-5% of patients will fail to achieve SVR and will require re-treatment options

• re-treatment is essential to prevent the long-term sequelae of HCV.

• Retreatment after development of resistance-associated substitutions, may be challenging

Case

• S.A is 66 years, female• HTN, DM• HCV diagnosed 2007• Genotype 4, F4

Medication

• Amlodpine• Carvidolol• Empagliflozin

Examination• conscious, oriented• No flapping tremor• BP 130/75• P 79• Afebrile• Chest : clear• Abdomen: soft, spleen palpable, no ascitis• CVS: S1+S2• Lower limb odema -ve

HB 8.5 Gm/dl

MCV 93 fL

PLT 47 10^3/uL

WBC 2.9 10^3/uL

Creat 0.8 mg/dL

Na 136 mmol/L

K 4 mmol/L

Urea 17 Mg/dl

INR 1.5 sec

HCV RNA 6432036 IU

ALB 2.7 g/dl

ALT 48 u/l

BILI 1.2 mmol/L

ALK 1.8 u/l

AST 31 u/l

GGT 111 u/l

AFP 13.2 IU/mL

• Sofosbuvir + Simeprevir for 12 weeks

• Relapsed

Examination• conscious, oriented• No flapping tremor• BP 136/89• P 82• Afebrile• Chest : clear• Abdomen: soft, spleen palpable, no ascitis• CVS: S1+S2• Lower limb odema -ve

HB 11 Gm/dl

MCV 95 fL

PLT 34 10^3/uL

WBC 2 10^3/uL

Creat 0.4 mg/dL

Na 134 mmol/L

K 3.7 mmol/L

Urea 14 Mg/dl

INR 1.3 sec

HCV RNA 22162262 IU

ALB 2.9 g/dl

ALT 22 u/l

BILI 1.1 mmol/L

ALK 80 u/l

AST 30 u/l

GGT 78 u/l

AFP 41 IU/mL

Abdominal ultrasound• Known case of liver cirrhosis with evidence of portal hypertension, grossly

splenomegaly ,multiple collaterals and minimal ascites. • Chronic Calcular cholycystitis

Upper endoscopysmall oesophageal varices,moderate portal hypertensive gastropathy

Options of treatment

A. SOF/VEL 12 weeksB. GLE/PIB 12 weeksC. SOF/VEL/VOXD. SOF/DAC/RIBE. SOF/LDVF. GZR/EBRG. OBV/PTV/r +

Sofosbuvir-Velpatasvir-Voxilaprevir in DAA-Experienced GT 1-6 POLARIS-4

Phase 3

Treatment Experienced

Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Source: Bourlière M, et al. N Engl J Med. 2017;376:2134-46.

Sofosbuvir-Velpatasvir-Voxilaprevir SVR12

Drug DosingSofosbuvir-Velpatasvir-Voxilaprevir (400/100/100 mg): fixed dose combination; one pill once dailySofosbuvir-Velpatasvir (400/100 mg): fixed dose combination; one pill once daily

GT 1-6 with prior DAA experience

(no NS5A inhibitor)n = 333

N=182

Sofosbuvir-Velpatasvir SVR12N=151

Week 0 12

GT 1, 2, 3 patients randomized 1:1. Stratified by presence of cirrhosis.Genotypes 4 were assigned to active arm (and not randomized). No GT 5, 6 patients were enrolled.

24

POLARIS

1-3

Baseline CharacteristicSOF-VEL-VOX

12 weeks(n = 182)

SOF-VEL12 weeks(n = 151)

Age, mean (range) 57 (25-85) 57 (24-80)

Male, n (%) 143 (79) 114 (75)

White, n (%) 160 (88) 131 (87)

Genotype, %11a1b

234

78 (43)54 (30)24 (13)31 (17)54 (30)19 (10)

66 (44)44 (29)22 (15)33 (22)52 (34)

0

Body mass index, mean, kg/m2 (range) 29 (18-45) 29 (18-53)

Mean HCV RNA, log10 IU/mL (range) 6.3 ± 0.6 6.3 ± 0.7

IL28B CC, n (%) 33 (18) 29 (19)

Cirrhosis, n (%) 84 (46) 69 (46)

POLARIS-4: Results

POLARIS-4: Overall SVR12 by Treatment Arm-4: Overall SVR12 by Treatment Arm


9790

0

20

40

60

80

100

SOF-VEL-VOX SOF-VEL

Patie

nts

(%) S

VR12

P<0.001 for superiority compared with prespecified 85% performance goal for SOF-VEL-VOX

136/151177/182

POLARIS-4: Results overall SVR 12 by treatment arm

POLARIS-4: Overall SVR12 by Treatment Arm


9790

0

20

40

60

80

100

SOF-VEL-VOX SOF-VEL

Patie

nts

(%) S

VR12

P<0.001 for superiority compared with prespecified 85% performance goal for SOF-VEL-VOX

136/151177/182

1 Relapse1 Death1 Lost to follow-up

1 Breakthrough14 Relapses

PPOLARIS-4: Results (SVR12 by Genotype)4: ResultsPOLARIS-4: Results

POLARIS-4: SVR12 by Genotype


98 96 10094

100

8995 97

85

0

20

40

60

80

100

GT 1a GT 1b GT 2 GT 3 GT 4

Patie

nts

(%) w

ith S

VR 1

2

SOF-VEL-VOX SOF-VEL

44/5251/5432/3331/3121/2223/2439/4453/54 0/019/19

POLARIS-4: Results (SVR12 by Cirrhosis Status)


9894

98

86

0

20

40

60

80

100

SOF-VEL-VOX SOF-VEL

Patie

nts

(%) w

ith S

VR 1

2

No Cirrhosis Cirrhosis

96/98 82/84 77/82 59/69

POLARIS-4: Result (Overall SVR by Baseline RAS)


94100 100 100 100

89 90 91 94

50

0

20

40

60

80

100

No RAS Any RAS NS3 Only NS5A Only NS3 + NS5A

Patie

nts

(%) w

ith S

VR 1

2

SOF-VEL-VOX SOF-VEL

32/3440/40

N=22 patients had NS5B RASs – all went on to achieve SVR12.No treatment-emergent RASs noted in the viral relapser on SOF/VEL/VOX. In SOF/VEL group, 10/15 developed Y93H or Y93C.

29/3239/3963/7083/8367/7584/89 2/44/4

Glecaprevir-Pibrentasvir in HCV GT 1 or 4 & Prior DAA TreatmentMAGELLAN-1 (Part 2)

Treatment-Experienced

Source: Poordad F, et al. Hepatology. 2018;67:1253-60.

Week 0 2812 2416


Glecaprevir-Pibrentasvir(300/120 mg) once dailyn = 44GT 1

(n = 87)

or

GT 4 (n = 4)

SVR12

SVR12n = 47 Glecaprevir-Pibrentasvir(300/120 mg) once daily

Randomized 1:1 ratio to 12 or 16 weeks; stratified by genotype and past NS5A experience

CharacteristicsGlecaprevir-Pibrentasvir

12 weeks(n = 44)

Glecaprevir-Pibrentasvir16 weeks

(n = 47)

Age, median years (range) 57 (22-67) 56 (36-70)Male sex, n (%) 31 (70) 33 (70)Black race, n (%) 9 (20) 11 (23)BMI, median kg/m2 (range) 28 (21-41) 29 (20-52)IL28B non-CC genotype, n (%) 38 (86) 42 (89)

HCV RNA, median log10 IU/ml (range) 6.1 (4.7-7.2) 6.3 (4.7-7.1)

HCV Subtype, n (%)1a1b1c4

35 (80)8 (18)

-1 (2)

32 (71)11 (23)

1 (2)3 (6)

Compensated cirrhosis, n (%) 15 (34) 12 (26)


CharacteristicsGlecaprevir-Pibrentasvir

12 weeks(n = 44)


(n = 47)

Prior DAA class, n (%)NS3/4A PI only (NS5A inhibitor naïve)NS5A inhibitor only (PI-naïve)N3/4A PI + NS5A inhibitor

14 (32)16 (36)14 (32)

13 (28)18 (30)16 (34)

Past DAA response, n (%)On-treatment failureVirologic relapse

14 (32)30 (68)

13 (28)34 (72)

Key baseline substitutions, n (%)NoneNS3 onlyNS5A onlyNS3 and NS5A

13 (30)2 (5)

24 (55)5 (11)

13 (30)4 (9)

23 (52)4 (9)


MAGELLAN-1 (Part 2): Results


89 91

0

20

40

60

80

100



Patie

nts

with

SVR

12

(%)

39/44 43/47

MAGELLAN-1 (Part 2): Results by Prior DAA Class

Sustained Virologic Response Based on Prior DAA Class

Prior DAA ClassGlecaprevir-Pibrentasvir

12 weeks(n = 44)


(n = 44)

NS3/4A PI only 14/14 (100) 13/13 (100)

NS5A inhibitor only 14/16 (88) 17/18 (94)

NS3/4A PI + NS5A inhibitor 11/14 (79) 13/16 (81)


Sustained Virologic Response Based on Baseline Substitutions

Baseline SubstitutionsGlecaprevir-Pibrentasvir

12 weeks(n = 44)


(n = 44)

None 13/13 (100) 13/13 (100)

NS3 only 2/2 (100) 4/4 (100)

NS5A only 20/24 (83) 22/23 (96)

NS3 and NS5A 4/5 (80) 1/4 (25)


Jan 2016

• Sofosbuvir + Daclatasvir and ribavirin for 24 weeks

• Week 4 HB 11.3 Gm/dlMCV 95 fLPLT 47 10^3/uLWBC 3.0 10^3/uLCreat 0.5 mg/dLNa 134 mmol/LK 4.0 mmol/LUrea 17 Mg/dlINR 1.4 secHCV RNA Not detected

• EOTHB 9.8 Gm/dlMCV 95 fLPLT 35 10^3/uLWBC 1.5 10^3/uLCreat 0.5 mg/dLNa 133 mmol/LK 3.9 mmol/LUrea 14 Mg/dlINR 1.5 secHCV RNA -VE

ALB 2.6 u/l

ALT 11 mmol/L

BILI 0.6 u/l

ALK 94 u/l

AST 23 u/l

• Week 24 post treatmentHB 11.5 Gm/dl

MCV 94 fL

PLT 41 10^3/uL

WBC 2.5 10^3/uL

Creat 0.5 mg/dL

Na 142 mmol/L

K 3.8 mmol/L

Urea 6 Mg/dl

INR 1.4 sec

HCV RNA -VE

ALB 2.6 g/dl

ALT 31 u/l

BILI 1.2 mmol/L

ALK 86 u/l

AST 30 u/l

GGT 89 u/l

AFP 36 IU/mL

1 year later

CT abdomen• Cirrhosis of liver with nodular parenchymal margins enlarged left and caudate

lobe of liver. There is small 1.8 x 1.7 cm size focal hypoechoic parenchymal lesion in the segment six of right hepatic lobe which reveals intense immediate arterial

• enhancement on post IV contrast study and early washout of contrast in the porto-venous phase.

Conclusion

• No specific algorithm to guide retreatment decision can be derived

• Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of SVR among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed

• Risk of HCC and liver-related mortality is significantly reduced, but not eliminated

• Patients with HCV who have virologic failure after treatment containing an NS5A inhibitor have limited retreatment options

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