Current approaches in the treatment of HCV GT 1b patient...

Current approaches in the treatment of

HCV GT 1b patient with extrahepatic

manifestations

Clinical case

Olga Sagalova St. Petersburg 03.06.2016 г.

2

Complaints in May 2016 г.: pain throughout the body, musculoskeletal pains in the area

below head, pain in the lumbar and lower thoracic spine region (more intensive at

inclinations), numbness in the hands at the night, feeling that hands “were pumped”,

hands hoot for fatigue, knee joint pains, tearfulness, irritability, weakness and hands

pains (impossibility of exact movements), sensitivity violations, dryness of a mucous

mouth, nose, eyes.

Anamnesis vitae:

1977 - the urolithic disease was diagnosed. A stone of the left kidney, the lithotomy is carried out.

1978 - acute pyelonephritis of left kidney, complicated by peritonitis, left nephrectomy was carried out.

Hemotransfusions

1982 - reflux in the stump of the ureter, resection of the stump.

1991 - the recurrence of renal colic on the right. Repeatedly hospitalized in urology department with a

diagnosis of urolithiasis. A single stone of the right kidney.

1994 – suspicion of acute pyelonephritis of right kidney complicated by sepsis. 03.1994 г. – right kidney

decapsulation.

During the next 10 years condition was stable.

F, 59 years

old, BMT – 24,9

HCV

GT1b

F3 pegIFN/RBV

treatment in

2008 – D/C

before EOT due

to AEs

3

Case history

0 5 10 15 20 25 30

Arthralgia

Years

1999 – HCV antibodies

Lichen planus

dryness of a mucous mouth, nose, eyes,

paresthesia

Liver biopsy: F1 (2008 г.) Antiviral treatment failed:pegintron/RBV 05.11.2008 –

24.12.2008 г. D/C due to AEs

2011: scleroderma, Sjogren syndrome

2015 г.: severe pain, polyneuropathy of the hands*, Lyrica 300 mg QD with a strong

temporary effect

* Electromyography in 2015 г.: signs of bilateral demyelinating lesions of sensory and motor fibers of the median nerve in the

distal no signs of damage at the level of the carpal channel.

4

Patient B, May 2016 г.: lichen planus of oral mucosa, inactive

phase

5

Laboratory findings in May 2016

F, 59 years

old

HCV

GT1b

F3 pegIFN/RBV

treatment in

2008

Parameter Meaning

Total bilirubin, µmol/l 8.7

Direct bilirubin, µmol/l 3.0

ALT, U/l 116

ASТ, U/l 110

GGTP, U/l 78.7

Ureа, µmol/l 5.7

Creatinine, µmol/l 81

Creatinine clearence, ml/min 61

МНО 1,01

Albumin, g/l 39.7

C-reactive protein, mg/l 7.5 (N = 0.0 – 5.0)

Crioglobulines Not detected

Hb, g/l 117

Plt, х 109/l 165

WBC, х 109/l 5,42

Results of instrumental

methods

Fibroscan 11.08.2015 г. - 11,8

kPa

MSCT of the abdomen

14.03.2016:

Liver has a normal size, shape,

with clear contours. The spleen is

not enlarged, cysts of the spleen..

CT features of a state after left

nephrectomy, scarring in the left

psoas muscle after drainage of

the hematoma, the vicar zoom,

nephrolithiasis (multiple

concretions from 3 to 9 mm in

diameter), a moderate expansion

of the CPPS of the right kidney..

6

Diagnosis: CHCV (GT 1b, IL-28B CT), minimal activity, F3 Metavir ( Fibroscan 11,8 kPa ).

Extrahepatic manifestations: Systemic scleroderma, a chronic course, limited form, minimal

activity with skin lesions (the"mask-like" face, a symptom of a "tobacco pouch"), blood vessels

(Raynaud's syndrome), joints (arthralgia), myalgia, gastrointestinal tract (esophagitis, chronic

hypokinetic colitis with constipation), cardiovascular system (incomplete intra-artrial blockade),

polyneuropathy of the upper extremities. Secondary Sjogren's syndrome (xerostomia,

xerophthalmia). Lichen planus of the oral mucosa, an inactive phase.

Co-morbidities: Urolithiasis. Chronic pyelonephritis of the one right kidney, the active

phase, CRF 0. CKD 2. Cyst of the retroperitoneal space. Percutaneous drainage in Sept 2015.

Osteoporosis without fractures T - 3.3. Scoliotic deformation of the spine. Osteochondrosis,

aggravation. Lumbalgia.

Hypertension, the risk 2. Bronchial asthma, mild persistent current, controlled current.

Respiratory failure 0.

Peptic ulcer of duodenum without exacerbation.

F, 59 years

old

HCV GT1b F3 pegIFN/RBV

treatment in

2008

7

Some of the extrahepatic manifestations of HCV infection

Mixed cryoglobulinemia syndrome Autoimmune mechanisms

Skin:

- cutaneous necrotising vasculitis;

- erythema nodosum;

- urticaria;

Renal:

- membranoproliferative glomerulonephritis.

Hematologic:

- non-Hodgkin's lymphoma.

Neuromuscular and joint:

- peripheral polyneuropathy;

- myopathic syndrome;

- arthritis, arthralgia

Skin:

- lichen planus (1,9%)

- porphyria cutanea tarda.

Endocrine:

-thyroiditis;

- diabetes mellitus etc.

Hematologic:

-autoimmune thrombocytopenia;

- aplastic anemia.

Autoimmune and other:

scleroderma and CREST syndrome;

- Sjogren's syndrome (2-11,9%)

8

1. Ombitasvir/paritaprevir/ritonavir (25/150/100 mg QD)

and dasabuvir (250 mg BD) 12 weeks

2. Simeprevir 150 mg + sofosbuvir 400 mg QD 12 weeks

3. Sofosbuvir 400 mg + daclatasvir 60 mg QD 12 weeks

4. Daclatasvir 60 mg + asunaprevir 100 mg QD 24 weeks

Which of the IFN- free regimens would you

prefer?

‡

9

Which factors should be taken into account while

choosing the antiviral treatment?

1. Stage of fibrosis.

2. Efficacy of antiviral treatment regimen

3. Potential drug-drug interactions.

4. Renal disease.

5. Extrahepatic manifestations

10

Efficacy of IFN-free regimens in HCV GT 1b pts

without cirrhosis

1. Kwo P, et al. 50th EASL; 2015. Abstract LB14

2. Dieterich D. et al, EASL, 2014, P0755

3. Colombo M. et al., 2014 AASLD, Abstract #1931

4. Zuckerman E. et al. EASL 2016. Abst. PS004

5. Sulkowski M. et al. N. Engl. J. Med. 2014; 370(3): 211-221

6.Pol S, et al. EASL 2015. L03

7.Kao JH. et al, Liver Int. 2015 Dec 18. doi: 10.1111/liv.13049. [Epub ahead of print]

8.Shuhei H. et al., EASL 2016, Abstract SAT 261

97 91

86,4

0

20

40

60

80

100

SOF+SIM 3D SOF+DAC DAC+ASV

clinical trials

real-world data

1

8

SV

R 1

2 ,%

2*

* including SOF+SIM+RBV regimen

** SVR 4 for pts without cirrhosis

3 4 5 6**

7 98 98.6 99 100 100

‡

http://www.ncbi.nlm.nih.gov/pubmed/24428467



11

Which factors should be taken into

account while choosing the antiviral

treatment?




4. Renal disease.


12

Current treatment:

-pregabalin (Lyrica) 300 mg QD,

- verapamil 120 mg QD,

- osteogenon 840 mg QD.

- tramadol ½ tablet QD

- risperidon 0,5 mg QD in the evening

F, 59 years

old

HCV GT1b F3 pegIFN/RBV

treatment in

2008

13

Potential drug-drug interactions

Drug SOF DAC SIM OBV/PTV/

r + DSV

ASV

Pregabalin - - - - -

Verapamil - + + + +

Tramadol - - + + +

Risperidon - - + + +

Osteogenon - - - - -

«-» - drug interactions are not expected

«+» - drug interactions are possible www.drugs.com/drug_interactions.html

14



treatment?




4. Renal disease.


15 Dumortier, AASLD, 2015, 1158

SOF-Based Therapy in HCV Patients with Severe Renal Failure

Retrospective study of SOF-based therapy in 50 patients with CHC with severe

renal failure (GFR < 35 mL/min) in France

France

n=50

Male, n (%) 36 (72)

Mean age, years 60.5±7.5

GT 1, n (%) 28 (56)

Cirrhosis, n (%) 27 (54)

Hemodialysis, n (%) 35 (70)

History of kidney transplantation, n (%) 17 (34)

History of liver transplantation, n (%) 11 (22)

On waiting list for kidney transplant, n (%) 27 (54)

Treatment naïve, n (%) 14 (28)

SOF+RBV, n (%) 7 (14)

SOF+PegIFN+RBV, n (%) 2 (4)

DCV+SOF±RBV, n (%) 30 (60)

SMV+SOF±RBV, n (%) 11 (22)

‡

90 88

0

20

40

60

80

100

SVR4 SVR12

Virologic Response (Interim Analysis)

Vir

olo

gic

resp

on

se,

%

Safety Results

GFR was not significantly modified

during treatment

Baseline: 29.6±6.2 mL/min

EOT: 27.9±6.5 mL/min

No cases of severe anaemia and

renal-related AE

16



treatment?




4. Renal disease.


17

Does successful antiHCV treatment with DAAs entail with reduction of extrahepatic manifestations?

Lichen planus:

– There are no published data regarding DAAs usage 1.

– Data regarding use of pegIFN/RBV are controversial 1

• Sjogren's syndrome:

There are no published data regarding DAAs usage.

Positive effect of pegIFN/RBV regimen has been registered in the limited number of observations 2

Scleroderma: There are no published data regarding DAAs usage

1. Sherman A .& Sherman K. Curr HIV/AIDS Rep (2015) 12:353–361

2. Doffoel-Hantz V. et al. La Revue de medecine interne / fondee

par la Societe nationale francaise de medecine interne. 2005;26:88–94.

18

1. Extrahepatic manifestations of HCV infection could be the main

indication for antiviral treatment even in the absence of significant liver

cirrhosis.

2. Taking into consideration the natural history of HCV infection and the

high efficacy of currently available regimens of antiviral drugs, the

treatment should be started at the early stage of disease to prevent the

development of severe fibrosis and extrahepatic manifestations. *.

3. In patients with severe co-morbidities it is necessary to choose the

most effective and safe IFN-free regimen taking into account potential

drug-drug interactions.

3. SOF-containing regimens are highly effective and well tolerated

options of treatment for “difficult –to-treat” patients.

* HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.

http://www.hcvguidelines.org/ Updated February 24, 2016

Conclusion

19

Thanks for your

attention

HCV genotype 2 infection: A case report

Professor Е. Esaulenko Saint-Petersburg State Pediatric Medical University

Genotype 2 is found worldwide, but is less common than genotype 1 and 3

Prevalence (Viremic)

0.0%-0.6%

0.6%-0.8%

0.8%-1.3%

1.3%-2.9%

2.9%-7.8%

North America Europe, Western Europe, Central Europe, Eastern Asia, Central Asia Pacific, High Income Asia, South

Asia, Southeast

Asia, East

Australasia

Sub-Saharan Africa, West Sub-S Africa, Southern Sub-S Africa, Central North Africa/Middle East Latin America, Andean Latin America, Southern

Latin America, Tropical

Latin America, Central

Caribbean

Razavi H, Gower E, Estes C, Hindman S. Global HCV Genotypes. Poster presented at: AASLD: The Liver Meeting 2013; 2013 Nov 1-5; Washington, DC, United States.

Prevalence of HCV genotype 2 in Russia

Country/Region %

Russia ~ 8,1% Pimenov et al., 2012

Russia ~ 4,4% Shustov et al., 2005

Russia, Moscow ~ 5,5% Vedernikov et al., 2010

Russia, Primorsky

region

~ 20% Sklyar et al., 2005

Russia, Saint-

Petersburg

~ 7,2% Zhebrun et al., 2011

3

In March 2016, patient was referred to the Clinical

Infectious Hospital named after Botkin, Saint- Petersburg, with:

1. high elevated liver enzymes: AlAT 350 U/L (reference range <

30 U/L);

2. positive HCV antibodies

3. PCR HCV +

4

Case report

Patient history & Examination in November 2015

County Russia

City St. Petersburg

Date of Birth 20/10/1952

Age, yr 63

Date anti-

HCV

15/11/2015

Reason for

testing: investigations

before surgery

Time of infection

and route of

transmission is

unknown

:

ALT 400 МЕ/L

Bilirubin 14 μmol/L

PCR HCV +

Genotyping and viral load were

not available

In November 2015 the patient

underwent cholecystectomy, which

was complicated by common bile duct

stricture.

5

Patient history & Examination in March 2016

ALT 350 МЕ/L

Bilirubin 12μmol/L

PCR HCV +

viral load

(HCV RNA

quantitative)

4x106 IU/mL

Genotype 2

Fibroscan F0

hemoglobin 110 g/L

platelet count 180x106 /L

Diagnosis:

Chronic hepatitis C,

replicative phase, GT2,

high cytolytic activity, F0

(Metavir)

6

Comorbidities

Chronic pancreatitis. Cholelithiasis. Choledocholithiasis, Bile duct stricture.

Arterial hypertension

– Losartan

Depressive Disorder

– Self-treatment with herbal OTC drugs

7

Will you treat this patient immediately or wait & monitor?

1. Treat now

2. Wait & monitor

8

EASL Recommendations on Treatment of Hepatitis C 2015

EASL Recommendations on Treatment of Hepatitis C 2015

In this case: the patient decided to start antiviral

treatment

9

Which treatment regimen would you choose in this GT2 HCV patient?

1. Pegylated IFN alpha 2 + Ribavirin

2. Pegylated IFN alpha 2 + Ribavirin +Sofosbuvir

3. Sofosbuvir + Ribavirin

4. Sofosbuvir + Daclatasvir

5. Daclatasvir + Asunaprevir

10

Treatment options recommended by EASL for patients with genotype 2 HCV infection:

•Daily sofosbuvir (400 mg) and weight-based RBV (1000-1200

mg) for 12 weeks);

• This regimen may be extended up to 16 or 20 weeks for

patients with cirrhosis, especially if treatment experienced

•Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 12 weeks,

In Russia, Peg IFN + RBV for 24 weeks is still a standard of care

in GT2 HCV patients

11

97

78

98

8291

62

0

20

40

60

80

100

SV

R12 (

%)

No cirrhosis Cirrhosis Overall

58/59 44/54 10/11 8/13 68/70 52/67

SOF+RBV 12 weeks PEG-IFN+RBV 24 weeks

Error bars represent 95% confidence intervals

GT 2 Treatment-Naïve SOF+RBV vs PEG-IFN+RBV

FISSION

Lawitz E, et al. N Engl J Med. 2013;368:1878–87. 12

Zeuzem S, et al. N Engl J Med 2014;370:1993–2001.

93

68/73 212/250

Overall

97 100 94 78

Naïve, Non-cirrhotic

Experienced, Non-cirrhotic

29/30 2/2 7/9 30/32

SV

R12 (

%)

Naïve, Cirrhotic

Experienced, Cirrhotic

0

20

40

60

80

100 Overall

Non-cirrhotic

Cirrhotic

HCV GT 2 TN and TE SOF + RBV for 12 Weeks

VALENCE

13

Thank you for attention!

14

Treatment of Chronic Hepatitis C with DAA in decompensated cirrhotic patient

with Wilson disease

T.Rozina

Lomonosov Moscow State University

I.M.Sechenov First Moscow State University

Wilson disease

Rare congenital condition with impaired copper metabolism, leading to metal accumulation and damage of the target organs

Orphan disease

Disease gene (АТР7В) is located in chromosome 13

Prevalence is 1:30 000 inhabitants1,2

Carrier frequency 1: 90, 1:1001,2

Autosomal recessive inheritance

1.Scheinberg H., Sternlieb I. Wilson's disease. In: Smith L.H. Jr., ed. Major problems in Internal Medicine. -Vol. 23. -WB Saunders Company. -Philadelphia, -1984. 2.Roberts E.A., Schilsky M.L. A practice guideline on Wilson disease.// Hepatology. -2003. -Vol. 37. -N 6. -P. 1475-92.

Target organs:

Eyes

Heart

Kidney

Liver Brain

Patient D., born in 1983 Scientific Centre of Neurology

Years 2010 2013 January February Tremor Gait and speech disturbances Platelets х109/l 59 Hemoglobin, g/l 138 AST, IU/l 38 ALT, IU/l 45 Bilirubin, μmol/л 25,1 Albumin, g/l 30 Spleen, mm 193 Diagnosis Treatment

Patient D., born in 1983 Scientific Centre of Neurology

Years 2010 2013 January February Tremor Gait and speech disturbances Platelets х109/l 59 Hemoglobin, g/l 138 AST, IU/l 38 ALT, IU/l 45 Bilirubin, μmol/л 25,1 Albumin, g/l 30 Spleen, mm 193 Diagnosis Wilson disease Treatment Zinc sulfate 620mg/day

Patient D., born in 1983 Scientific Centre of Neurology City Hospitals N 52, 20

Years 2010 2013 2014 January February September January Tremor Gait and speech disturbances Platelets х109/l 59 61 Hemoglobin, g/l 138 134 AST, IU/l 38 63 ALT, IU/l 45 91 Bilirubin, μmol/л 25,1 26,4 Albumin, g/l 30 39 Spleen, mm 193 Diagnosis Wilson disease Treatment Zinc sulfate 620mg/day

Traumat i c Brain Injury

Patient D., born in 1983 Scientific Centre of Neurology City Hospitals N 52, 20

Years 2010 2013 2014 January February September January February Tremor Gait and speech disturbances Platelets х109/l 59 61 Hemoglobin, g/l 138 134 - 68 - 90 AST, IU/l 38 63 44 ALT, IU/l 45 91 55 Bilirubin, μmol/л 25,1 26,4 Albumin, g/l 30 39 Spleen, mm 193 Diagnosis Wilson disease Variceal bleeding Treatment Zinc sulfate 620mg/day Blood transfusions

Traumatic

brain Injury

GIB

Ligation

of

Varices

ASCITES

HBsAg – Anti-HCV –

Patient D, born in 1983 Tareev named Clinic of Sechenov First Moscow State Medical University

Years 2014 March April Tremor Gait and speech disturbances Ascites Hgb, g/l 87 AST, IU/l 47 ALT, IU/l 56 Bilirubin, μmol/l 18 Albumin, g/l 29 Prothrombin, % 78 Diagnosis Wilson disease: liver cirrhosis Child B, portal hypertension (ascites, splenomegaly, variceal bleeding, ligation of esophageal varices) Treatment Zinc sulfate 620 mg/day D-penicillamine 250 mg/day


Years 2014 March April Tremor Gait and speech disturbances Ascites Hgb, g/l 87 95 AST, IU/l 47 520 ALT, IU/l 56 536 Bilirubin, μmol/l 18 43,6 Albumin, g/l 29 36 Prothrombin, % 78 Diagnosis Wilson disease: decompensated liver cirrhosis Treatment Zinc sulfate 620 mg/day D-penicillamine 250 mg/day


Years 2014 March April Tremor Gait and speech disturbances Ascites Hgb, g/l 87 95 AST, IU/l 47 520 334 ALT, IU/l 56 536 385 Bilirubin, μmol/l 18 43,6 40 Albumin, g/l 29 36 38 Prothrombin, % 78 46 Diagnosis Wilson disease: decompensated liver cirrhosis Acute Hepatitis С Treatment Zinc sulfate 620 - 372 mg/day D-penicillamine 250 – 500 mg/day

HAV, HEV – HBV –

HCV RNA +, genotype 3

Which strategy would you prefer?

1. Symptomatic treatment

2. Increasing of Penicillamine dosage

3. To stop Penicillamine, because transaminases elevation can be caused by Penicillamine (DILI)

4. Immediate start of antiviral treatment

5. Wait 12 weeks for spontaneous HCV-clearance, than antiviral treatment if viremic


Years 2014 2015 March April May July March June September Tremor Gait and speech disturbances Ascites Hgb, g/l 87 95 117 139 146 148 160 AST, IU/l 47 520 334 105 55 42 448 414 315 296 208 ALT, IU/l 56 536 385 137 64 49 598 583 376 464 396 Bilirubin, μmol/l 18 43,6 40 21 24 34,7 42 37 53 39 Albumin, g/l 29 36 38 40 42 45 41 45 Prothrombin, % 78 46 48 46 55 Diagnosis Wilson disease: decompensated liver cirrhosis Chronic Hepatitis С Treatment Zinc sulfate 620 - 372 - 248mg/day Stopped D-penicillamine 250 – 500 – 750 – 1000 – 1500 - 1500 - 1500mg/day



HAV, HEV – HBV, CMV, EBV –

Database of Tareev named Clinic (1985-2016)

• 181 patient • 140 (77,3%) – liver cirrhosis, 79 (43,6%) –

decompensated liver cirrhosis • No cases with concomitant chronic HBV-infection • 3 patients with concomitant HCV-infection

1. Chronic hepatitis С, genotype 2, relapse after IFN + RIB 24 weeks. Now takes SOF + DAC

2. Acute hepatitis С, treated with SOF + RIB 24 weeks, SVR 3. Clinical case

In literature: Nałecz A. et al 1995, Lembowicz K. et al. 1999.

https://www.ncbi.nlm.nih.gov/pubmed/10086916


Years 2014 2015 March April May July March June September Tremor Gait and speech disturbances Ascites Hgb, g/l 87 95 117 139 146 148 160 AST, IU/l 47 520 334 105 55 42 448 414 315 296 208 ALT, IU/l 56 536 385 137 64 49 598 583 376 464 396 Bilirubin, μmol/l 18 43,6 40 21 24 34,7 42 37 53 39 Albumin, g/l 29 36 38 40 42 45 41 45 Prothrombin, % 78 46 48 46 55 Diagnosis Wilson disease: decompensated liver cirrhosis Chronic Hepatitis С Treatment Zinc sulfate 620 - 372 - 248mg/day Stopped D-penicillamine 250 – 500 – 750 – 1000 – 1500 - 1500 - 1500mg/day



HAV, HEV – HBV, CMV, EBV –

AVT

Which type of treatment would you prefer?

1. PegIFN + Ribavirin 24 week

2. PegIFN + Ribavirin + Sofosbuvir 12 weeks

3. Sofosbuvir + Daclatasvir 12 weeks

4. Sofosbuvir + Ribavirin 24 weeks

5. Sofosbuvir + Daclatasvir 24 weeks

6. Sofosbuvir + Daclatasvir + Ribavirin 24 weeks

EASL Guideline for Cirrhotic Patients

European Association for the Study of the Liver (EASL). Recommendations on Treatment of Hepatitis C 2015, Journal of Hepatology, Vol. 63, Issue 1, p199–236

SOF + PEG-RBV

SMV + PEG-RBV

SOF + RBV

SOF + LDV

PAR/р + OMB +

DAS

PAR/р + OMB

SOF + SMV

SOF + DCV

GT 1а 12 w

12 w (naives or relapsers)

or 24 w (partial or null responders)

No 12 w with RBV or 24 w w/o RBV or 24 w with RBV in

negative predictive factors ответа

24 w with RBV No 12 w with

RBV or 24 w w/o RBV

12 w with RBV or 24

w w/o RBV

GT 1b No 12 w with RBV No

GT 2 12 w No

12 w (naives or

relapsers) or 24 w

(partial or null responders)

No No No No 12 w w/o RBV

GT 3 12 w No No No No No No 24 w with RBV

GT 4 12 w

12 w (naives or relapsers)

or 24 w (partial or null responders)

No

12 w with RBV or 24 w w/o RBV or 24 w with RBV in


No 24 w with RBV

12 w with RBV or

24 w w/o RBV

12 w with RBV or

24 w w/o RBV

GT 5-6 12 w No No

12 w with RBV or 24 w w/o RBV or 24 w with RBV in


No No No

Drug-drug interactions

www.hep-druginteractions.org

Lab Tests during Antiviral Treatment

Week 0 Week 4 Week 12 Week 24 Follow up

Week 4 Follow up Week 12

AST 208 33 30 33 36 32

ALT 396 38 29 28 31 36

Hgb 160 134 130 129 144 145

Bilirubin 42 42 37 46 19 49

HCV RNA 2,2 x 104 IU/ml

0 0 0 0 0

2015 2016

Conclusions:

• SVR 12 achieved

• Drug-drug interactions between Penicillamine with Sofosbuvir and Daclatasvir are not expected

• No clinically significant AE

• Cirrhosis compensation achieved due to concomitant treatment with Penicillamine and DAA

Long-term Prognosis in Wilson Disease

Study N Duration of

follow up, years Stable course Survival

Merle U et al., 20071

Germany 163 17 (1-51) 76% 98%

Svetel M et al., 20092 Serbia

142 11 79% 80%

Lowette KF, 20103 Belgium

24 15 92% 92 %

Bruha R, 20114 Czech Republic

117 12 (1-41) 82% -

1 Merle U et al. Gut. 2007;56(1):115-20; 2 Svetel M et al. Eur J Neurol. 2009;16(7):852-7; 3 Lowette KF et al. Eur J Gastroenterol Hepatol. 2010 May;22(5):564-71. 4 Bruha R et al. Liver Int. 2011;31(1):83-91

Current approaches in the treatment of HCV GT 1b patient...

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