CAN ELASTOGRAPHY BE USED IN ALL LIVER DISEASES?

Transcription

1 CAN ELASTOGRAPHY BE USED IN ALL LIVER DISEASES? INTERNATIONAL HEPATOLOGY ULTRASOUND COURSE UNIVERSITY COLLEGE OF LONDON ROYAL FREE HOSPITAL 01-03/06/2018 Dr Ma&eo Rosselli, MD PhD UCL Ins(tute for Liver and Diges(ve Health Royal Free Hospital London

2 INTRODUCTION Elastography is used to assess non invasively liver disease at the (me of diagnosis and follow up. It is used to predict the severity of portal hypertension and pa(ents outcome. Liver s(ffness measurements are not always the same in terms of cutoff values (there are inter- ae(ology and intra- ae(ology differences). It is not always easy to have reliable measurements and some (mes we cannot obtain meaningful results. This presenta(on aims to highlight these differences, difficul(es and provide further insights on the mul(faceted nature of liver disease and the clinical approach to non invasive assessment.

3 INTRODUCTION The feasibility and reliability of liver elastography depend on Liver related factors The amount of fibrosis and its distribu(on Confounding factors (inflamma(on, cholestasis, conges(on ) Inter- e(ology and intra- e(ology differences (difficulty in defining specific elastography cutoff values)

4 INTRODUCTION Pa(ent/technical related factors Narrow intercostal spaces Ascites Breath holding Skin to capsule distance Waist circumference ( 102 cm) and High BMI ( 30)

5 F1 F2 F3 F4 Pellicoro et al. Liver fibrosis and repair: immune regula(on of wound healing in a solid organ. Nature Reviews, Immunology. 2014; 14:

6 ALD HBV PSC HCV NAFLD PSC PBC PSC

7 Fibrosis distribution in explanted cirrhotic livers 50.0 CPA - % ALD PBC PSC AIH Aetiology HCV HBV Figure 4. Box and whisker plots (median and IQ range in rectangle, 275 correlation is not the same as assessing the degree of agreement of measurements,22 which is the most relevant factor when considering an assay to quantify histological fibrosis. We have shown for the first time (Figure 2) that there is a good agreement between L and R lobes, as virtually all points are within the 95% limits of agreement with a bias of only 1.35%, which was less than the median intra-observer error of 2%. Therefore, although statistical significance can be attached to higher R lobe CPA (P = 0.039), the bias is only 1.35%, which is clinically insignificant when compared to the intra-observer error of 2% and the overall CPA range of 8 47%. When assessed individually, none of the aetiologies of liver disease in this study showed statistically significantly more fibrosis in one lobe compared to the other, although the sample population in this study for each aetiology is small (n = 10). PBC, PSC and HCV had a higher median CPA in the R lobe than the L lobe and ALD, AIH and HBV showed that slightly more fibrosis was present in the L lobe. Therefore, from a

8 ALD

9 ALCOHOL LIVER DISEASE Alcohol related toxic effect and inflamma(on Raised liver s(ffness values not solely related to fibrosis* Reversibility of inflamma(on and s(ffness values ader alcohol withdrawal** and possible regression of cirrhosis with abs(nence Difficult follow up because of the effect of ac(ve alcohol intake *Mueller S, Millonig G, Sarovska L, et al. Increased liver s(ffness in alcoholic liver disease: differen(a(ng fibrosis from steatohepa((s. World J Gastroenterol 2010; 16: **Trabut JB, Thepot V, Nalpas B, et al. Rapid decline of liver s(ffness following alcohol withdrawal in heavy drinkers. Alcohol Clin Exp Res 2012;36:

10 ALCOHOL LIVER DISEASE Fernandez et al. Transient elastography using Fibroscan is the most reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in alcoholic liver disease. Eur J Gastroenterol Hepatol Sep;27(9):

11 ALCOHOL LIVER DISEASE A systema(c review from the Cochrane Collabora(on, based on 5 retrospec(ve and 9 prospec(ve cohort studies with a total of 834 pa(ents, suggests that TE may be used as a diagnos(c method to rule out severe fibrosis or cirrhosis in pa(ents with ALD using cut- offs of 9.5 and 12.5kPa* Recent work highlights very good correla(on of TE and 2DSWE to diagnose significant fibrosis and cirrhosis with cutoff values of 9.6 and 19.7 kpa for TE and 10.2 and 16.4 kpa for 2DSWE** *Pavlov et al. Transient elastography for diagnosis of stages of hepa(c fibrosis and cirrhosis in people with alcoholic liver disease. Cochrane Database Syst Rev 2015;(1):CD **Thiele et al. Transient and 2- Dimensional Shear- Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis. Gastroenterology 2016;150:

12 74.5 kpa 61.6 kpa

13 PRIMARY BILIARY CHOLANGITIS Autoimmune liver disease Affects the distal bile ducts with inflamma(on and periductal fibrosis Patchy distribu(on of fibrosis Presinusoidal portal hypertension Cirrhosis

14 PRIMARY BILIARY CHOLANGITIS *F1 7.1 kpa F2 8.8 kpa F kpa F kpa *Corpechot et al. Noninvasive elastography- based assessment of liver fibrosis progression and prognosis in primary biliary cirrhosis Hepatology. 2012;56(1):

15 PRIMARY BILIARY CHOLANGITIS kpa 23.4 kpa 15.6 kpa 25.5 kpa

16 11.7 kpa 8.69 kpa 13.0 kpa Discrepancy between the liver irregular echostructure/morphology and szffness values which are relazvely low and variable liver szffness

17 CPH and PBC LIVER STIFFNESS 41.6 kpa 10.5 kpa SD = 11.4 kpa Med =22.5 kpa

18 The venogram shows a veno- venous intra- hepazc shunt. HVPG is low despite the presence of cirrhosis FHVP = 3 mmhg WHVP = 6 mmhg HVPG = 3 mmhg

19 PBC SPLEEN STIFFNESS SD = 27.9 kpa Med = kpa

20 PRIMARY BILIARY CHOLANGITIS The available data is scarce compared to other ae(ologies but provides clinical guidance However there is high variability due to the patchy distribu(on of fibrosis and liver s(ffness per se might in some cases underes(mate fibrosis Presinusoidal portal hypertension should always be suspected.

21 PRIMARY SCLEROSING CHOLANGITIS Chronic cholesta(c liver disease of unknown cause Inflamma(on of the intra and/or extra- hepa(c bile ducts which leads to biliary fibrosis It is typically a segmental/regional disease Periportal fibrosis Cirrhosis

22 PRIMARY SCLEROSING CHOLANGITIS *F1 7.4 kpa F2 8.6 kpa F3 9.6 kpa F kpa *Corperchot et al. Baseline values and changes in liver s(ffness measured by transient elastography are associated with severity of fibrosis and outcomes of pa(ents with primary sclerosing cholangi(s. Gastroenterology 2014;146(4):970-9.

23 M O R F O L O G I C DIFFERENCES IN PRIMARY S C L E R O S I N G CHOLANGITIS

24 LS kpa LS kpa

25 LS 4.22 kpa

26 6.9 kpa

27 SEVERE DISSOCIATION OF THE BILIARY TREE 22.6 kpa 37.3 kpa 72 kpa 206 kpa

28 PRIMARY SCLEROSING CHOLANGITIS There is evidence of correla(on between defined s(ffness values and fibrosis S(ffness measurement follow up might provide prognos(c informa(on Cholestasis has a high impact on s(ffness values and we do not know for sure how much of it is due to inflamma(on or established fibrosis The segmental distribu(on of disease might underes(mate the severity of PSC if we rely on s(ffness values which might have sampled a normal area of liver parenchyma.

29 AUTOIMMUNE HEPATITIS

30 AUTOIMMUNE HEPATITIS The natural history of autoimmune hepa((s is extremely heterogenic and might change from an indolent form with mild fibro(c changes to progressive parenchymal sclerosis and cirrhosis with portal hypertension. It might be characterized by inflammatory flares or an aggressive panern with diffuse necrosis which may lead to acute/subacute liver failure or cirrhosis. The (ming of treatment and response leads to the residual parenchymal appearance and func(onal reserve.

31 AUTOIMMUNE HEPATITIS Liver s(ffness has been reported to be very high in AIH, likely to be secondary to inflamma(on* Fibrosis and cirrhosis can be reversible in this seong and elastography is a reliable follow- up tool to monitor also disease ac(vity** *Hartl et al. Transient elastography in autoimmune hepa((s: Timing determines the impact of inflamma(on and fibrosis. J Hepatol. 2016; 65(4): **Hartl et al. Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepa((s. J. Hepatol. 2018, 68,

32 AUTOIMMUNE HEPATITIS

33 AUTOIMMUNE HEPATITIS CIRRHOSIS 29.9 kpa 23.0 kpa

34 5.37 kpa 6.56 kpa

35 Linle elas(fica(on of t h e a r e a s w i t h panacinar necrosis. P o r t a l t r a c t s highlighted by dense well- formed elas(n Elas(fied panacinar n e c r o s i s w i t h r e g e n e r a ( n g nodules Panacinar necrosis. No viable liver parenchyma. Basic underlying lobular architecture preserved with iden(fiable portal tracts H e p a t o c y t e n o d u l e s separated by thick fibrous s e p t a w i t h m a r k e d ductular prolifera(on and a m i l d, m a i n l y l y m p h o p l a s m a c y ( c inflammatory infiltrate

36 LS 11.6 kpa LS kpa LS kpa

37 LS 5.82 kpa LS 6.06 kpa

38 NAFLD RELATED CHRONIC LIVER DISEASE

39

40 Metabolic syndrome NAFLD HepaZc steatosis NASH NAFLD fibrosis - cirrosi

41 Dietrich CF et al. EFSUMB Guidelines and Recommenda(ons on the Clinical use of Liver Elastography Ultraschall in Med 2017; 38: e16 e47 DIFFERENCES BETWEEN ELASTOGRAMS AND ULTRASOUND IMAGES Ultrasound scanering occurs at the large- scale structural level, it also arises at the cellular level and does not require the structure to be connected. Shear wave will not propagate across zero fric(on breaks in the structural matrix. For example, a dilute suspension of cells in saline will scaner ultrasound but will not support a shear deforma(on or a shear wave. Finally, unlike the situa(on for ultrasound propaga(on and scanering, the shear modulus of most (ssues increases with vascular and inters((al pressure. These features might make elastography sensi(ve to the presence of disease in situa(ons where conven(onal ultrasound imaging fails to detect it. On the contrary back scanering might generate a heterogenic echo- panern according to the underlying (ssue architecture but the physical characteris(cs might fall within the normality range.

42 NAFLD RELATED CHRONIC LIVER DISEASE LS 3.99 kpa LS kpa LS kpa

43 PREDICTION

44 CAP >300 db/m and LS CAP >340 db/m and LS INCREASED RISK OF FALSE POSITIVE RESULTS FOR F3- F4 INCREASED RISK OF FALSE POSITIVE RESULTS FOR F3- F4 Pe&a et Al, Hepatology 2017;65(4):

45 NAFLD DIAGNOSTIC ALGORYTHM NAFLD Fibrosis Score (NFS) EsZmates the amount of scarring based on several lab tests. Formula: X age X BMI x IFG/Diabetes (Yes = 1; no = 0) X AST/ALT razo X platelet X albumin NFS < =F0- F2 NFS indetermined NFS > = F3- F4 Castera et al Nat Review Gastroenterol Hepatol 2013; 10:666-75

46 LIMITING FACTORS FOR MEASURING STIFFNESS IN NAFLD The distribu(on of inflamma(on within steato(c liver and hence the evolu(on towards fibrosis might be irregular leading to variable readings and poten(ally lower accuracy. Increased BMI (> 30Kg/m 2 ) makes transient elastography measurement challenging. The use of XL probe reduces the rate of failed measurements in obese subjects. Annalisa Berzigoo. Geong closer to a point- of- care diagnos(c assessment in pa(ents with chronic liver disease: Controlled anenua(on parameter for steatosis. Journal of Hepatology 2014.; 60:

47 LIMITING FACTORS FOR MEASURING STIFFNESS IN NAFLD However a skin to capsule distance > 3.4 cm and a very high BMI such as 40 Kg/m 2 make failure rate very high even with XL proble. Visceral fat might displace the liver leading to difficult measurements. Pa(ent might have difficul(es in laying down and breathing leading to inability to breath hold which is very important par(cularly in pswe and 2DSWE. Annalisa Berzigoo. Geong closer to a point- of- care diagnos(c assessment in pa(ents with chronic liver disease: Controlled anenua(on parameter for steatosis. Journal of Hepatology 2014.; 60:

48 LIMITING FACTORS FOR MEASURING STIFFNESS IN NAFLD Hepa(c steatosis might affect other liver ae(ologies. Hence quan(fica(on of hepa(c steatosis should be considered in every ae(ology since it might influence s(ffness measurements as well as par(cipate to the progression of fibrosis

49 CONCLUSIONS Elastography can be used in all liver diseases but not without taking into account the clinical scenario. If used as a single diagnos(c tool there are risks of obtaining misleading results. This risk is higher in AIH, PBC and especially in PSC. In ALD always consider ac(ve alcohol intake and the (me of withdrawel Although promising results are available, NAFLD is associated to technical limits which are par(cularly challenging and need to be recognized and overcome.

50 THANK YOU!