signiﬁcant ﬁbrosis predicts new-onset diabetes mellitus ......hbx pres2/s prec/pgrna pres1...

Significant fibrosis predicts new-onset diabetes mellitusand arterial hypertension in patients with NASH

Graphical abstract

NAFLD-related significant fibrosis as a determinant of metabolic outcomesin non-diabetic non-hypertensive patients

Cumulative incidence

1-year - 0.7%3-year - 2.1%5-year - 3.5%

1-year - 0.7%3-year - 2.8%5-year – 4.2%

1-year – 2.9%3-year – 11.4%5-year – 14.3%

1-year – 2.9%3-year – 14.3%5-year – 17.1%

Mild fibrosis (F0-F1)

Significant fibrosis (F2-F4)

Type 2 diabetes mellitus Arterial hypertension

N = 143

N = 35

Annual incidence

Significant fibrosis (F2-F4) Obesity (BMI >30)

7 cases/100 person-years 6.7 cases/100 person-years

Type 2 diabetes mellitus Arterial hypertension

Highlights� NAFLD-related significant fibrosis predicts the occurrence of

type 2 diabetes mellitus and arterial hypertension.

� The annual incidence of metabolic outcomes is four-timeshigher in the presence of significant fibrosis.

� Neither steatosis nor NASH predict the appearance of metabolicoutcomes.

� Hepamet fibrosis score >0.12 is associated with the risk ofdeveloping type 2 diabetes mellitus.

Authors

Javier Ampuero, Rocío Aller,Rocío Gallego-Durán, ., Javier Salmerón,Juan Turnes, Manuel Romero Gómez

[email protected] (J. Ampuero),[email protected] (M. RomeroGómez).

Lay summaryPatients with biopsy-proven non-alco-holic fatty liver disease and significantfibrosis were at risk of developing type 2diabetes mellitus and arterial hyper-tension. The risk of metabolic outcomesin patients with significant fibrosis wasincreased in the presence of obesity. Inaddition to liver biopsy, patients atintermediate-to-high risk of significantfibrosis by Hepamet fibrosis score wereat risk of type 2 diabetes mellitus.

Research ArticleNAFLD and Alcohol-Related Liver Diseases

July 2020

https://doi.org/10.1016/j.jhep.2020.02.028 e1© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. J. Hepatol. 2020, 73, 17–25

Selonsertib for patients with bridging fibrosis orcompensated cirrhosis due to NASH: Results from

randomized phase III STELLAR trials

Graphical abstract

≥1-stage fibrosisimprovement

NASH resolutionwithout worsening

fibrosis

≥1-stage fibrosisimprovement

NASH resolutionwithout worsening

fibrosis

0

5

10

15

20

25

Prop

ortio

nof

patie

nts

(95%

CI)

SEL18 mg

SEL6 mg Placebo SEL

18 mgSEL6 mg Placebo

44/321 26/159 14/321 14/159

1314

16

54

9

p=0.56p=0.59

p=0.25p=0.14

SEL18 mg

SEL6 mg Placebo SEL

18 mgSEL6 mg Placebo

59/351 27/172 13/351 7/172

p=0.29p=0.67

p=0.37p=0.86

1917

16

44

2

STELLAR-3 STELLAR-4

41/322 16/322 67/354 8/354

Highlights� Selonsertib was safe and inhibited its target (ASK1) but did not

lead to fibrosis regression or reduce disease progression in NASH.

� Improvement in liver fibrosis on biopsy was associated withimprovement only in other histologic features.

� Improvements in ELF score and liver stiffness by transient elas-tography correlated with a variety of clinical parameters.

Authors

Stephen A. Harrison, Vincent Wai-Sun Wong, Takeshi Okanoue, .,Zachary Goodman, Eric J. Lawitz,Zobair Younossi

[email protected](S.A. Harrison).

Lay summaryPatients with non-alcoholic steatohe-patitis (NASH) can develop scarring ofthe liver (fibrosis), including cirrhosis,which increases the risks of liver fail-ure and liver cancer. We testedwhether 48 weeks of treatment withselonsertib reduced fibrosis in patientswith NASH and advanced liver scar-ring. We did not find that selonsertibreduced fibrosis in these patients.

Research ArticleNAFLD and Alcohol-Related Liver Diseases

https://doi.org/10.1016/j.jhep.2020.02.027 e2© 2020 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. J. Hepatol. 2020, 73, 26–39

Full-length 5’RACE identifies all major HBV transcripts inHBV-infected hepatocytes and patient serum

Graphical abstract

m7Gppp

pDephosphorylation of degraded mRNARemoval of 5'Cap

Anchor ligation

RT with first gene specific primer Gsp1

PCR with anchor primer andsecond gene specific primer Gsp2

Capped transcriptspecific amplicons

pAAAAA

pAAAAA

pAAAAA

HBx

preS2/S

preC/pgRNApreS1

Intracellularviral RNAs

Full length HBV 5'RACE

Encapsidatedviral RNAs

pgRNASpliced pgRNA

Different HBxtranscripts

Circulatingviral RNAs

321

pgRNASpliced pgRNA

Different HBxtranscripts

pAAAAA

preS

1

preS2S

HBx

preC/pg

cccDNA

Highlights� HBV full-length 5’RACE discriminates all viral transcripts

including HBx.

� Viral particles contain pgRNA, pgRNA splice variants anddifferent HBx RNAs.

� HBx RNAs in viral particles are both capped and uncapped.

� The composition of circulating viral RNA species can varyamong patients.

Authors

Bernd Stadelmayer, Audrey Diederichs,Fleur Chapus, ., Kara Carter,Barbara Testoni, Fabien Zoulim

[email protected](B. Stadelmayer), [email protected](F. Zoulim).

Lay summaryEspecially under infection conditions, ithas been difficult to study the differenthepatitis B virus transcripts in depth. Thisstudy introduces a new method that canbe used in any standard lab to discriminateall hepatitis B viral transcripts in cell cul-ture and in the serum of patients.

Research ArticleViral Hepatitis


Hepatitis B core-specific memory B cell responsesassociate with clinical parameters in patients with

chronic HBV

Graphical abstract

0

6

9

3

IT IA IC ENEG

HBcAgHBsAg <<x 17.8 1.030.058

HBsAg Dylight650

HBs

Ag D

ylig

ht55

0

NUC

HBcAb (Serum)

HBcAb SFC (ELISPOT)

HBcAg+ B cells (FACS)

HBV DNA(log IU/ml)

ALT(ULN)

Blood CD19+ B cell Blood CD19+ B cellHBcAg Dylight650

HBc

Ag D

ylig

ht55

0

Highlights� B cell responses in chronic HBV are predominantly directed against

HBcAg, not HBsAg.

� HBcAg-specific memory B cells associate with HBV’s clinical phases.

� HBcAg-specific B cell responses are reduced during antiviral treatment.

Authors

Thomas Vanwolleghem, ZwierM.A. Groothuismink,Kim Kreefft, Magdeleine Hung,Nikolai Novikov, Andre Boonstra

[email protected](T. Vanwolleghem).

Lay summaryIn recent years, studies examin-ing the role of B cells duringchronic hepatitis B virus infec-tion have regained interest. Weshow that circulating B cellsmore often target the hepatitis Bcore antigen than the hepatitissurface antigen. Moreover, thesehepatitis B core-specific B cellsassociate with the natural his-tory of chronic HBV, and theirresponses decline during effec-tive antiviral treatment.



Hepatitis B-related outcomes following direct-actingantiviral therapy in Taiwanese patients with chronic

HBV/HCV co-infection

Graphical abstract

DAA

HCVXDAADAA

HBV

HCV

HBV±NUC

HBV

HBVHBVX

HCV/HBV dual infections

HCV SVR + HBsAg loss

HCV SVR + stable HBV

HCV SVR + HBV reactivation

10%

52%

38%20% (6/30) HBV

clinical flare

33% (2/6) death

Highlights� HBsAg levels decline during DAA therapy and rebound post-DAA

therapy in HBV/HCV coinfected patients.

� HBsAg loss can occur in HBV/HCV coinfected patients on DAAtherapy at a frequency seen in HBV monoinfection.

� HBV/HCV-coinfected patients are at risk of HBV reactivation afterDAA, especially in those with higher HBsAg levels.

� HBV/HCV coinfected cirrhotic patients on DAAs should undergoHBV prophylaxis to reduce risk of hepatic failure and death.

� Quantitative HBsAg measurement could guide decision-making inHBV/HCV coinfected patients on DAA therapy.

Authors

Ming-Lun Yeh, Chung-Feng Huang,Ching-I. Huang, ., Wan-Long Chuang,Raymond T. Chung, Ming-Lung Yu

[email protected] (M.-L. Yu).

Lay summaryWe studied outcomes relating to hep-atitis B virus (HBV) in patients coin-fected with both hepatitis B and C.Patients receiving direct-acting anti-viral treatment for hepatitis C weremore likely to experience seroclear-ance (or functional cure of HBV), butwere also more likely to experienceHBV reactivation, which can lead tohepatitis, liver failure and death. Incoinfected cirrhotic patients beingtreated for HCV, prophylactic treat-ment for HBV is mandatory.


https://doi.org/10.1016/j.jhep.2020.01.027 e5© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/). J. Hepatol. 2020, 73, 62–71

IFNL3-adjuvanted HCV DNA vaccine reduces regulatory Tcell frequency and increases virus-specific T cell

responses

Graphical abstract

NS4B

NS5ANS3/4A

IFNL3 plasmid

Vaccination in chronicHCV patientsNCT02027116

CD4+ and CD8+ T cells

Regulatory T cells

Cytokine production (IFN-γ, TNF, and IL-2)

Total Treg frequency Activated Treg frequency

CTLA-4 expression

Vaccination inDAA-treated SVR subjects

NCT03674125

Prevention of HCV reinfection ?

HCV non-structural (NS) plasmids

HCV DNA vaccine(GLS-6150)

+

Highlights� DAAs successfully induce SVR in chronic HCV infection, but a

prophylactic HCV vaccine is still warranted.

� We report here the first-in-human study demonstrating safetyof an IFNL3-adjuvanted HCV DNA vaccine.

� IFNL3-adjuvanted HCV DNA vaccine reduces Treg cell frequencyand increases virus-specific T-cell responses.

� Ex vivo IFN-k3 treatment decreases Treg cell frequency in pre-vaccinated PBMCs, which might be an indirect effect by pDCs.

Authors

Ji Won Han, Pil Soo Sung, Seon-Hui Hong,., Jeong Heo, Sang Hoon Ahn, Eui-Cheol Shin

[email protected] (E.-C. Shin), [email protected] (S.H. Ahn), [email protected](J. Heo).

Lay summaryAlthough direct-acting antivirals(DAAs) are successfully used for thetreatment of chronic hepatitis C virus(HCV) infection, a prophylactic HCVvaccine needs to be developed, espe-cially for patients who achieve a sus-tained virologic response. In the currentstudy, we show that a DNA vaccine(GLS-6150) was safe and increasedHCV-specific T cell responses. A clinicaltrial is underway to test this vaccine inpatients with a sustained virologicresponse following DAA therapy.



Genotype correlates with the natural history of severebile salt export pump deficiency

Graphical abstract

0 5 10 150

20

40

60

80

100

% o

f pat

ient

sal

ive

with

nat

ive

liver

p <0.001

18

BSEP1At least one p.D482G or p.E297G mutation (residual function in BSEP)

BSEP2At least one missensemutation, yet not p.D482G or p.E297G

BSEP3Mutations leading to atruncated or non-functionalprotein

0 5 10 150

10

20

30

40

18Age (years)

% o

f pat

ient

s w

ithhe

pato

cellu

lar c

arci

nom

a

BSEP 3BSEP 2BSEP 1

p = 0.001

Highlights� NAPPED is the largest global database of genotyped patients

with BSEP deficiency.

� The genotype of patients with BSEP deficiency predictssurvival with native liver.

� Genotype predicts long-term benefit of interruption ofenterohepatic circulation.

� Serum bile acids can be a surrogate marker for long-termoutcome.

� Treatment of patients with BSEP deficiency should be basedon genotype.

Authors

Daan B.E. van Wessel, Richard J. Thompson,Emmanuel Gonzales, ., Ton M.G. Bunt,Bettina E. Hansen, Henkjan J. Verkade

[email protected] (H.J. Verkade).

Lay summaryThis study presents data from the largestgenetically defined cohort of patients withsevere bile salt export pump deficiency todate. The genotype of patients with severebile salt export pump deficiency is asso-ciated with clinical outcomes and the suc-cess of therapeutic interventions. Therefore,genotypic data should be used to guidepersonalized clinical care throughoutchildhood and adulthood in patients withthis disease.

Research ArticleDILI, Autoimmune, Cholestatic and Genetic Diseases


A randomized, placebo-controlled, phase II study ofobeticholic acid for primary sclerosing cholangitis

Graphical abstract

Placebo

OCA 5-10 mgOCA 1.5-3.0 mg

-200

-150

-100

-50

0

50

Weeks

ALP

(U/L

) LS

mea

n (S

E) c

hang

e fro

m b

asel

ine

*

* p <0.05

***

0 2 6 12 14 18 24

Study design

Placebo

1.5 mg OCA

5 mg OCA

3.0 mg OCA

10 mg OCA

Screening≤30 days

from day 0

Randomization

12 weeks 12 weeks

2-Yearopen-labelLTSE

Titration visit

Highlights� Novel treatments for PSC are an urgent unmet need.

� This phase II study evaluated OCA in patients with PSC.

� OCA 5–10 mg significantly reduced serum ALP levels at 24weeks.

� The safety profile of OCA was consistent with previousstudies.

Authors

Kris V. Kowdley, Raj Vuppalanchi,Cynthia Levy, ., Leigh MacConell,David Shapiro, Christopher L. Bowlus

[email protected](K.V. Kowdley).

Lay summaryPrimary sclerosing cholangitis (PSC) is along-term disease that damages the bileducts in the liver over time. In the AESOPclinical study in patients with PSC, obe-ticholic acid reduced serum alkalinephosphatase (a potential marker of diseaseseverity) during an initial 24-week treat-ment period. The result was sustainedduring the 2-year, long-term extension ofthe study. The most common side effect ofobeticholic acid in the study was itchyskin, which is consistent with earlierclinical studies.

Research ArticleDILI, Autoimmune, Cholestatic and Genetic Diseases

https://doi.org/10.1016/j.jhep.2020.02.033 e8© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/). J. Hepatol. 2020, 73, 94–101

Toll-like receptor 4 is a therapeutic target for preventionand treatment of liver failure

Graphical abstract

Acute liverfailure

Acute-on-chronicliver failure

TLR4 TLR4

TLR4 signaling inhibitionTAK-242

Lipopolysaccharide (LPS)

Apoptotic cell deathsystemic inflammation

Necrotic cell deathsystemic inflammation

Highlights� Cirrhosis is associated with TLR4-related sensitization to

endotoxins and a switch from apoptotic to necroptotic celldeath.

� Inhibition of TLR4 signaling by TAK-242 reduces immune cellresponses and hepatocyte injury in response to LPS in vitro.

� In models of acute and acute-on-chronic liver failure, TAK-242 mitigated LPS-driven systemic inflammation and organinjury.

Authors

Cornelius Engelmann, Mohammed Sheikh,Shreya Sharma, ., Saurabh Gupta,Fausto Andreola, Rajiv Jalan

[email protected] (R. Jalan).

Lay summaryToll-like receptor 4 (or TLR4) mediatesendotoxin-induced tissue injury in liverfailure and cirrhosis. This receptor sensi-tizes cells to endotoxins, which are pro-duced by gram-negative bacteria. Thus,inhibiting TLR4 signaling with an inhibitor(TAK-242) ameliorates organ injury andsystemic inflammation in rodent models ofacute and acute-on-chronic liver failure.

Research ArticleCirrhosis and Liver Failure


HDL-related biomarkers are robust predictors ofsurvival in patients with chronic liver failure

Graphical abstract

Stable cirrhosis228 patients

enrolled at Medical University of Graz

Acute decompensation280 patients

enrolled in CANONIC cohortincluding 107 patients with ACLF

Measurement ofHDL-relatedbiomarkers(HDL-C, apoA-I)

at baseline

Chr

onic

live

r fai

lure

Follo

w-u

p 12

mon

ths

HD

L-C

Apo

A-I

Cum

ulat

ive

surv

ival

Months

0.2

0.0

0.4

0.6

0.8

1.0

0 2 4 6 8 10 12

p <0.001

>17 mg/dl≤17 mg/dl

Cum

ulat

ive

surv

ival

Months

0.2

0.0

0.4

0.6

0.8

1.0

0 2 4 6 8 10 12

p <0.001

>50 mg/dl≤50 mg/dl

Exte

rnal

val

idat

ion

in98

5pa

tient

sen

rolle

dat

Med

ical

Uni

vers

ity o

fVie

nna

Highlights� HDL levels are profoundly decreased in chronic liver failure.

� HDL-related biomarkers (HDL-C, apoA-I) are robust predictors ofdisease progression and survival.

� The prognostic value of single HDL-related biomarkers is verysimilar to that of the composite scores.

� HDL-related biomarkers correlated inversely with markers ofinflammation.

Authors

Markus Trieb, Florian Rainer,Vanessa Stadlbauer, ., Joan Clària,Gunther Marsche, Rudolf E. Stauber

[email protected](G. Marsche), [email protected] (R.E. Stauber).

Lay summaryPeople who suffer from cirrhosis(scarring of the liver) have low levelsof cholesterol carried by high-densitylipoproteins (HDL-C). These alter-ations are connected to inflammation,which is a problem in severe liverdisease. Herein, we show that reducedlevels of HDL-C and apolipoprotein A-I(apoA-I, the main protein carried byHDL) are closely linked to the severityof liver failure, its complications andsurvival. Both HDL-C and apoA-I canbe easily measured in clinical labo-ratories and are as good as currentlyused prognostic scores calculatedfrom several laboratory values bycomplex formulas.

Research ArticleCirrhosis and Liver Failure

https://doi.org/10.1016/j.jhep.2020.01.026 e10© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/). J. Hepatol. 2020, 73, 113–120

Stereotactic body radiation therapy vs. radiofrequencyablation in Asian patients with hepatocellular

carcinoma

Graphical abstract

Multinationalretrospective study

Propensity score matching

SBRT 496 tumorsRFA 1,568 tumors

SBRT 313 tumorsRFA 313 tumors

Cumulatvelocal recurrence

Gray's test, p<0.0010

20

40

60

80

100

0 12 24 36 48 60 72Time (Months)

Cum

ulat

ive

inci

denc

e of

loca

l pro

gres

sion

(%)

SBRTRFA

313 236 153 90 43 17 5313 197 134 84 49 26 14RFA

SBRTNo. at risk

Gray's test, p<0.0010

20

40

60

80

100

0 12 24 36 48 60 72Time (Months)

Cum

ulat

ive

inci

denc

e of

loca

l pro

gres

sion

(%)

SBRTRFA

496 315 200 121 64 28 101,568 1,086 771 501 294 155 62RFA

SBRTNo. at risk

1,568 1,086 771 501 22994 15RFAF

SBRT RFA

Highlights� SBRT provided better local control than RFA among patients with

HCC.

� Toxicity rates and survival outcomes were similar between thesetreatment modalities.

� SBRT is an effective alternative to RFA for larger tumors (>3 cm) ina subphrenic location (especially segment 8).

Authors

Nalee Kim, Jason Cheng, Inkyung Jung,., Seok Jae Heo, Jong Yoon Won,Jinsil Seong

[email protected] (J. Seong).

Lay summaryIt is currently not known what thebest treatment option is for patientswith unresectable hepatocellular car-cinoma. Here, we show that stereo-tactic body radiation therapy providesbetter local control than radio-frequency ablation, with comparabletoxicities. Stereotactic body radiationtherapy appears to be an effectivealternative to radiofrequency ablationthat should be considered when thereis a higher risk of local recurrence ortoxicity after radiofrequency ablation.

Research ArticleHepatic and Biliary Cancer


Portopulmonary hypertension in the current era ofpulmonary hypertension management

Graphical abstract

60

40

20

Surv

ival

(%)

0

80

100

Months since PoPH diagnosis0 12 24 36 48 60

Transplanted patientsNo indication for LTIndication for LT but nottransplanted

Survival by liver transplant (LT) status

Overall survival

Cohort of 637 patients withportopulmonary hypertension

Initial PAH therapy in574 patients (90.1%)

Effect of oral PAH therapies on pulmonary vascular resistance

Endothelin receptor

antagonist

Phosphodiesterase-5inhibitors

Oral combination

therapy

-37%-40% -64%

Portopulmonary hypertension

Pulmonary vascular remodeling

Highlights� Portopulmonary hypertension is a severe complication of portal

hypertension.

� Therapies targeting pulmonary arterial hypertension improve car-diopulmonary haemodynamics.

� Combining these therapies and liver transplantation is associated withexcellent long-term outcomes.

Authors

Laurent Savale,Manuel Guimas,Nathan Ebstein, .,Marc Humbert, Pascal DeGroote, Olivier Sitbon

[email protected](L. Savale).

Lay summaryPortopulmonary hyperten-sion is defined by the pres-ence of pulmonary arterialhypertension in the contextof chronic liver disease and ischaracterized by progressiveshortness of breath andexercise limitation. The pres-ence of severe pulmonaryarterial hypertension in livertransplant candidates repre-sents a contraindication forsuch a surgery; however,treatments targeting pulmo-naryarterialhypertensionareefficacious, allowing for safetransplantation and confer-ring good survival outcomesin those who undergo livertransplantation.

Research ArticleLiver Transplantation


Exercise retards hepatocarcinogenesis in obese miceindependently of weight control

Graphical abstract

Lean WT mice Obese diabeticfoz/foz mice

DEN injection

Sedentary mice

No HCC HCC in 7/11 mice

Lean WT mice Obese diabeticfoz/foz mice

DEN injection

Volountary exercise

HCC in 1/12 mice HCC in 2/13 mice

6 months

Highlights� Obesity and insulin resistance accelerate liver cancer onset in foz/foz mice.

� Mice with an in-cage exercise wheel engage in physical activity that abolishesthe effect of obesity on hepatocarcinogenesis.

� Pair-fed foz/foz mice exhibit similar weight gain but are not protected.

� Exercise decreases proliferation of dysplastic hepatocytes by activating p53 toinduce p27.

� A critical pathogenic role of JNK1 was also confirmed using Jnk1-/-.foz/foz mice.

Authors

Arfianti Arfianti,Sharon Pok, Vanessa Barn,., George N. Ioannou,Narci C-H. Teoh, GeoffreyC. Farrell

[email protected](G.C. Farrell).

Lay summaryFatty liver disease com-monly occurs alongsideobesity and diabetes, con-tributing to rapidlyincreasing rates of livercancer throughout theworld.Herein,weshowthatexercise reduces the inci-dence and progression ofhepatocellular carcinomainmousemodels.Theeffectof exercise on cancer riskwasshowntobeindepend-ent of changes in weight.Exercise could be a pro-tectivemechanismagainstliver cancer in at-riskindividuals.

Research ArticleExperimental and Translational Hepatology


Hepatic stellate cell activation promotes alcohol-induced steatohepatitis through Igfbp3 and SerpinA12

Graphical abstract

Lipogenicgenes

↓SerpinA12NRP-1 ↓pAMPK

Hepatic stellate cell

Hepatocyte

↑pAkt

↑IGFBP3Integrin

Ethanol

Synectin

Highlights� HSCs regulate hepatocyte steatosis that precedes liver fib-

rosis in alcohol-related liver disease.

� HSC-derived Igfbp3 and SerpinA12 mediate lipid dropletformation in hepatocytes.

� These results are recapitulated in samples from patients withalcoholic hepatitis.

Authors

Juan P. Arab, Daniel Cabrera, TejasavS. Sehrawat, ., Marco Arrese, RobertC. Huebert, Vijay H. Shah

[email protected] (V.H. Shah).

Lay summaryHepatic stellate cells are known for theirrole in fibrosis (scarring of the liver). In thisstudy, we describe their role in the modu-lation of fat deposition and inflammation inthe liver, which occurs secondary to alcoholdamage.

Research ArticleExperimental and Translational Hepatology


[18F]-Alfatide PET imaging of integrin avb3 for thenon-invasive quantification of liver fibrosis

Graphical abstract

Tail intravenous injection

Micro-PET/CT

PET/CT scan

[18F]-Alfatidebiodistribution

[18F]-Alfatideuptake

Hepatic integrinαvβ3 expression

Monitor liver fibrosis

18FAlfatide

18FAlfatide

Highlights� [18F]-Alfatide was demonstrated to bind specifically with integrin avb3

(mainly expressed on activated HSCs).

� [18F]-Alfatide can detect fibrosis progression both in animal liver fibroticmodels and human liver tissues.

� Imaging integrin avb3 with PET/[18F]-Alfatide offers a potential non-invasivemethod for monitoring fibrosis progression.

Authors

Tuo Shao, Zhen Chen,Vasily Belov, .,Xiaoyuan Chen, RaymondT. Chung, Steven H. Liang

[email protected] (S.H. Liang),[email protected](R.T. Chung), [email protected] (X. Chen).

Lay summaryIntegrinavb3expressiononactivated hepatic stellatecells (aHSCs) is associatedwith HSC proliferation dur-ing hepatic fibrogenesis.Herein, we show that aradioactive tracer, [18F]-Alfatide, binds to integrinavb3 with high affinity andspecificity. [18F]-Alfatidecould thusbeusedasanon-invasive imagingbiomarkerto track hepatic fibrosisprogression.

Research ArticleInnovative Diagnostics, Modelling and Digital Hepatology


signiﬁcant ﬁbrosis predicts new-onset diabetes mellitus ......hbx pres2/s prec/pgrna pres1...

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