Hepatic Medicine: Evidence and Research Dovepress

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REVIEW

Approaches to the Diagnosis of Portal

Hypertension: Non-Invasive or Invasive Tests?
This article was published in the following Dove Press journal:
Hepatic Medicine: Evidence and Research

Elton Dajti 1,2 Abstract: Portal hypertension is the main driver of complications in patients with advanced
Luigina Vanessa Alemanni 1,2 chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient
Giovanni Marasco 1,2 measurement (HVPG) >5 mmHg. Values of HVPG ≥10 mmHg determine the presence of
Marco Montagnani 1,2 clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal
bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and
Francesco Azzaroli 1,2
requires high expertise, so its routine use outside third level centers or clinical trials is limited. In
1
IRCCS Azienda Ospedaliero-Universitaria the last decades, several non-invasive tests (NITs) have been developed and validated for the
di Bologna, Bologna, Italy; 2Department of
Medical and Surgical Sciences (DIMEC), diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement
University of Bologna, Bologna, Italy (SSM) are the most promising tools available, as they have been proven accurate to predict
CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In
the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time
for diagnosis of CSPH (LSM >20-25 kPa) and the screening of patients with a low probability of
having high-risk varices (LSM <20 kPa and platelet count >150.000/mm3). In this review, we
aimed to summarize the growing evidence supporting the use of non-invasive tests for the
evaluation of portal hypertension in patients with chronic liver disease.
Keywords: liver stiffness, spleen stiffness, portal hypertension, hepatic venous pressure
gradient, liver cirrhosis

Introduction
Liver cirrhosis is a major cause of morbidity and mortality worldwide and is associated
with increasing health burden and costs.1 It is a very heterogeneous and dynamic
condition, and at least two distinct stages should be recognized: compensated and
decompensated cirrhosis.2 Decompensation includes the development of clinical events
such as ascites, variceal bleeding, hepatic encephalopathy, or hepato-renal syndrome, and
it is associated with a significant decrease in patient survival.3 Cirrhosis in the compen­
sated phase, on the other hand, is associated with an up to 80% 5-year survival rate; it can
be further classified according to the degree of portal hypertension, as evaluated by its
gold standard,4 the hepatic venous pressure gradient (HVPG), in compensated cirrhosis
without portal hypertension (HVPG <5 mmHg), with mild portal hypertension (HVPG
>5 mmHg, but <10 mmHg), or clinically significant portal hypertension (CSPH, and
HVPG ≥10).5 The development of CPSH is an important hallmark in the natural history
of liver cirrhosis and is associated with an increased risk of gastroesophageal varices,
Correspondence: Francesco Azzaroli hepatic decompensation, hepatocellular carcinoma (HCC), and mortality.5
IRCCS Azienda Ospedaliero-Universitaria In this view, early identification of patients with compensated cirrhosis and risk
di Bologna, Bologna, Italy
Email francesco.azzaroli@unibo.it stratification according to the severity of portal hypertension is of extreme

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importance for the hepatologist. In the last years, several to NSBB to guide therapy for the prevention of variceal
non-invasive tests have been developed and validated for bleeding recurrence.13
these purposes, with liver (LSM) and spleen stiffness Besides, recently, the PREDESCI trial14 showed that
measurement (SSM) being the most promising tools NSBB could significantly improve decompensation-free
available.6 In the present paper, we aim to summarize the survival in patients with compensated cirrhosis and
pros and cons and the evidence supporting the use of both HVPG ≥10 mmHg, with criteria similar to those adopted
invasive and non-invasive tests (NITs) in the diagnosis of for assessing hemodynamic response for HRV, since these
portal hypertension. patients were those who most benefited from NSBB.
Regarding HVPG prospective evaluations, one of the
main applications is related to the evaluation of patency
Part I – Invasive Evaluation of Portal and therapeutic effectiveness after transjugular intrahepatic
Hypertension: The Hepatic Venous portosystemic shunt (TIPS) placement, which is indicated
Pressure Gradient in patients with decompensated portal hypertension.15
It is widely recognized that patients with compensated Interestingly, dynamic HVPG changes have been pro­
advanced chronic liver disease (ACLD) may progress to spectively reported in other settings, such as in patients
decompensation at a rate of about 5–7% per year.7 The with hepatitis C virus (HCV)-associated cirrhosis treated
leading cause of decompensation is the development of with the new direct-acting antiviral agents (DAAs), show­
portal hypertension and its complications such as variceal ing that sustained virologic response (SVR) was associated
bleeding, hepatic encephalopathy, and ascites, thus impact­ with a significant reduction of HVPG when compared with
ing on overall patient mortality rate.8 that assessed before treatment, thus mirroring both hemo­
The gold standard method used for the evaluation of portal dynamic and fibrotic changes occurring after treatment.16
hypertension is the measurement of HVPG, which has been Also, the portal hypertension degree influences the natural
widely validated also as a prognostic factor.9 Portal hyperten­ history of chronic liver diseases, leading to HCC.10
sion is defined by HVPG values> 5 mmHg; HVPG ≥10 Previously, an HVPG value >10mmHg has been identified
mmHg is associated with clinically significant portal hyperten­ as independently associated with HCC occurrence.10,17,18
sion (CSPH), which is an at-risk condition for decompensa­ Finally, HVPG value has been associated with out­
tion, esophageal varices, and HCC development.4,5,10 Severe comes in patients with cirrhosis undergoing elective extra­
PH is defined by HVPG > 12 mmHg, whereas very severe PH hepatic surgery, allowing an accurate patients risk
by HVPG >16 mmHg; these conditions are both associated stratification thus improving post-surgical outcomes.19
with a higher risk of variceal bleeding and mortality.4 Briefly, However, HVPG use is limited by its invasiveness and is
through venous access, a catheter is introduced into the right available only in highly specialized centers; thus, in the
brachial vein or the right internal jugular vein until a branch of last decade, several attempts have been made to find the
ideal NIT able to replace HVPG.
the hepatic veins is reached, usually the median or the right
vein. Afterward, a balloon is inflated occluding all the vessels
below, and then the measurement of wedged hepatic vein Part II – Non-Invasive Evaluation of
pressure is performed.11 Subsequently, after deflating the bal­ Portal Hypertension
loon at the tip of the catheter, the free hepatic vein pressure is The last decade has seen several efforts to develop tests
measured.4,11 that can replace invasive methods for the assessment of
Non-selective beta-blockers (NSBB) represent the portal hypertension in patients with ACLD. Patients were
most common therapeutic choice for the primary and routinely subjected to liver biopsies in order to establish
secondary prophylaxis of variceal bleeding.2 HVPG mea­ the severity of fibrosis, and HVPG measurement is still
surement is also employed for the prediction of acute and considered the gold standard in portal hypertension
chronic hemodynamic response to NSBB therapy for high- evaluation.4 However, as mentioned above, these methods
risk varices (HRV).4 According to the Baveno VI consen­ are invasive, not widely available, and risky for patients.
sus, the response to NSBB is defined as the reduction of Such limitations have led to the development and valida­
HVPG ≥10% or ≤12 mmHg after treatment.12 Moreover, tion of new alternative NITs which have revolutionized the
HVPG may be used to assess the hemodynamic response clinical approach to ACLD patients. The increasing need

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Dovepress Dajti et al

for NITs in patients with liver cirrhosis has also been seminal paper by Colecchia et al:28 SSM provided the
recently highlighted by the guidelines of the European strongest correlation with HVPG (r = 0.885), as compared
Society for the Study of the Liver (EASL).20 to LSM. A recent meta-analysis confirmed the good corre­
Novel elastographic techniques have got increasing lation between SSM and HVPG.29 Therefore, SSM is con­
attention through the years and today play a well- sidered today as a direct surrogate of portal hypertension
recognized role in liver disease assessment, as stated also that captures all of its physiopathological components, from
by the last Baveno VI Consensus Workshop.2 Among ultra­ early to the late cirrhotic stages. From a technical point of
sound-based elastographic techniques, transient elastogra­ view, SSM values are obtained using the same probe used to
phy (TE) is the first and the most validated method for perform LS, with the patient in a supine position with
LSM evaluation.21 Liver stiffness represents a surrogate maximal abduction of the left arm and the probe positioned
marker of liver fibrosis; therefore, it is useful in diagnosing in an intercostal space where the spleen was correctly
ACLD and its complications (Table 1). Being liver fibrosis visualized by ultrasound. Since no specific reliability cri­
a fundamental determinant of hepatic resistance to the portal teria have been developed for SSM, the same as those for
blood flow,6 LSM application has been consequently LSM are generally applied; besides, SSM is not considered
extended to portal hypertension assessment and the predic­ reliable if the splenic parenchymal thickness is <4 cm under
tion of esophageal varices (EV) with good results; in fact, the probe. The main limit of SSM is its feasibility since the
LSM represents today a valuable non-invasive alternative to rate of technical failure reported in current literature is
HVPG in clinical practice. One of the first pieces of evi­ highly variable (0–60%). However, in expert centers, this
dence was produced by Carrión et al in 2006 in HCV- rate is usually <10%.30,31 Moreover, new devices including
patients undergoing liver transplantation;22 LSM by TE build-in ultrasound for spleen detection32 or fusion-
technique showed a close correlation with HVPG and good methods,33 have been developed to improve SSM feasibil­
accuracy (AUC=0.93) in diagnosing portal hypertension ity and accuracy in the prediction of portal hypertension.
(defined as HVPG > 6 mmHg). It was followed by several Besides elastography techniques, several serum biomar­
studies aimed at establishing the optimal LS cut-off for kers and radiological scores have been developed to non-
portal hypertension diagnosis, obtaining controversial invasively detect liver fibrosis34 and portal hypertension.35–43
results. A recent meta-analysis still confirmed the good For instance, the aspartate aminotransferase (AST) to Platelet
correlation between LSM and HVPG (r = 0.783).23 Ratio Index (APRI) and Fibrosis (FIB-4) Score showed an
However, Vizzutti et al reported that, while the correla­ AUROC of was 0.728 and 0.710, respectively, for the pre­
tion between LSM and HVPG values less than 10–12 diction of large varices in a meta-analysis.44 Several studies
mmHg was excellent (r = 0.81–0.91), it appeared to be evaluated also more direct surrogates of portal hypertension,
poorer for higher HVPG values, with a non-optimal linear such as von Willebrand factor39,40 or indocyanine green
regression analysis (r2=0.35 for HVPG > 10 mmHg, clearance45,46 showing more promising results. However,
r2=0.17 if > 12 mmHg).24 A possible explanation is that the modest correlation with HVGP47 and overall suboptimal
in an early phase portal hypertension is mainly linked to performance of the above-mentioned readily available serum
fibrotic modifications of liver parenchyma, but at later biomarkers, as well as the limited evidence and availability
stages, it is determined by many hemodynamic changes of other more direct biomarkers, hampers the routine use of
driven, such as neoangiogenesis, hyperdynamic circula­ such NITs for the detection of portal hypertension and its
tion, portosystemic collateral development, and splanchnic complications in everyday clinical practice.40
vasodilation,6 and these modifications are not captured by
an indirect surrogate of portal hypertension, such as LSM.
More recently, increasing attention has been driven to
Liver and Spleen Stiffness for the
the evaluation of SSM by elastosonography. It is today clear Diagnosis of Clinically Significant Portal
that splenomegaly does not simply reflect spleen congestion Hypertension
in ACLD patients, but it is determined also by structural The identification of CSPH is fundamental in ACLD since
changes and tissue hyperplasia due to fibrogenesis, angio­ it allows to identify the patients who are at increased risk
genesis, activation of lymphoid compartment.25–27 of gastroesophageal varices, decompensation, HCC, and
Consensually, SSM proved to have a strong correlation mortality.5 With the introduction of LSM in clinical prac­
with the whole range of HVPG values, as shown in the tice, many attempts have been made to establish the best

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Table 1 Performance of Liver and Spleen Stiffness in the Diagnosis of CSPH and Gastroesophageal Varices
Author, Year Study Design Nr. Patients Technique Parameter Outcome AUROC Cut-Offs Performance
(Rule-Out or
Rule-In)

Carrion, 200622 Prospective 129, HCV TE LSM PH 0.930 8.74 kPa Sens 100%
Spec 60.8%

Vizzutti, 200724 Retrospective 61, HCV TE LSM CSPH 0.990 13.6 kPa Sens 97%,
Spec 92%

48
Reiberger, 2012 Retrospective 502, mixed TE LSM CSPH 0.871 18 kPa Sens 82.2%
Spec 83.4%

Salz, 201449 Prospective 88, mixed p-SWE LSM CSPH 0.855 2.58 m/s Sens 71.4%
Spec 87.5%

EV 0.743 2.74 m/s Sens 62.5%

Spec 89.5%

Procopet, 201550 Prospective 88, mixed 2D-SWE LSM CSPH 0.858 17 kPa Sens 80.8%
Spec 82.1%

Maurice, 201666 Retrospective 310, mixed TE LSM CSPH 0.746 <20 kPa and PLT 33% spared
>150.000 EGDS

78
Bae, 2018 Retrospective 1035, mixed TE LSM HRV N/A <20 kPa and PLT 21% spared
>150.000 EGDS

Augustin, 201872 Retrospective 925, Mixed TE LSM HRV N/A <20 kPa and PLT 21% spared
>150.000 EGDS

<25 kPa and PLT 40% spared

>110.000 EGDS

Moctezuma-Velazquez, Retrospective 227, PBC or TE LSM HRV N/A <20 kPa and PLT 36.1% spared
201870 PSC >150.000 EGDS

Petta, 201865 Retrospective 790, NAFLD TE LSM HRV N/A <20 kPa and PLT 33.3% spared
>150.000 EGDS

76
Berger, 2020 Retrospective 2368, mixed TE LSM HRV N/A <20 kPa and PLT 24% spared
>150.000 EGDS

Hirooka, 201155 Prospective 60, mixed RTE LSM CSPH 0.832 N/A N/A

SSM CSPH 0.978 8.24 m/s Sens 96%

Colecchia, 201228 Prospective 100, HCV TE LSM CSPH 0.920 <16 kPa Sens 96.2%
>24.2 kPa Spec 97.9%

EV 0.899 <16.4 kPa Sens 95.4%

>25 kPa Spec 97.1%

SSM CSPH 0.966 <40 kPa Sens 98.5%

>52.8 kPa Spec 97.1%

EV 0.941 <41.3 kPa Sens 98.1%

>55 kPa Spec 95.7%

Takuma, 201354 Prospective 340, mixed p-SWE LSM EV 0.746 1.87 m/s Sens 99.2.%

SSM EV 0.933 3.18 m/s Sens 98.9%

(Continued)

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Table 1 (Continued).

Author, Year Study Design Nr. Patients Technique Parameter Outcome AUROC Cut-Offs Performance
(Rule-Out or
Rule-In)

Takuma, 201652 Prospective 60, viral p-SWE LSM CSPH 0.833 N/A N/A

SSM CSPH 0.943 3.1 m/s Sens 97.1%

Elkrief, 201758 Prospective 191, mixed 2D-SWE LSM CSPH 0.80 <16 kPa Sens 95%
>38 kPa Spec 52%

SSM CSPH 0.61 <26.6 kPa

>27.9 kPa

Colecchia, 201830 Retrospective, 613, mixed TE LSM HRV 0.768 <20 kPa + 21.7% spared
Prospective >PLT 150.000 EGDS

SSM HRV 0.837 ≤46 kPa 35.8% spared

EGDS

Baveno VI + SSM HRV N/A Combined model 43.8% spared

46 kPa EGDS

Wang, 202031 Prospective 341, HBV TE LSM HRV N/A <20 kPa + 37% spared
> PLT 150.000 EGDS

SSM HRV N/A ≤46 kPa 52.8% spared

EGDS

Baveno VI + SSM HRV N/A Combined model 61.6% spared

46 kPa EGDS

Abbreviations: 2D-SWE, two-dimensional share wave elastography; AUROC, area under ROC curve; CSPH, clinically significant portal hypertension; HBV, hepatitis
B virus; HCV, hepatitis C virus; HRV, high-risk varices; EGDS, esophagogastroduodenoscopy; EV, esophageal varices; LSM, liver stiffness measurement; N/A, not available;
NAFLD, non-alcoholic fatty liver disease; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; PLT, platelet count; p-SWE, point-share wave elastography;
Sens, sensitivity; Spec, specificity; SSM, spleen stiffness measurement; TE, transient elastography.

LSM values to rule-in and rule-out CSPH.24,48–50 In 2017, performance in diagnosing CSPH (AUC = 0.92) and
a meta-analysis confirmed the good performance of LS in severe PH (AUC = 0.87), with elevated sensitivity (respec­
predicting CSPH (AUC=0.921) for low cut-off values of tively 88% and 92%) and specificity (84% and 79%).29
13.6–18 kPa.23 Another meta-analysis highlighted that an Among other elastographic techniques, promising results
LSM value <13.6 kPa assessed by TE resulted valuable to have been observed as well. LSM and SSM evaluated by
rule-out CSPH with high sensitivity (>90-95%), while the Acoustic Radiation Force Impulse (ARFI)52–55 were able to
cutoff value > 22 kPa provided the overall best perfor­ diagnose HVPG ≥ 10 mmHg and HVPG ≥ 12 mmHg with
mance and appeared to accurately confirm CSPH (specifi­ similarly high diagnostic performance (LSM, AUC = 0.93
city > 90–95%).51 The last Baveno VI Consensus and 0.87, respectively; SSM, AUC = 0.97 and 0.95).56
Workshop of 2015 recommended the use of LSM in clin­ Promising results were found for LSM assessed by 2-dimen­
ical practice, suggesting LSM values >15 kPa as highly sional shear wave elastography (2D-SWE)57,58 or Magnetic
suggestive of cACLD and ≥20-25 kPa as sufficient to rule- Resonance Elastography (MRE) as well,59–61 even if further
in CSPH, alone or combined to platelets count and spleen evidence to better identify the optimal cutoffs for CSPH and
size in virus-related chronic liver disease.2 the best application fields is needed.
Being a direct surrogate of portal hypertension, SSM
showed a strong correlation with the whole range of
HVPG values.28 Colecchia et al28 proposed values of 40 Liver and Spleen Stiffness for the
kPa and 52.8 kPa to respectively rule-out (sensitivity Diagnosis of High-Risk Esophageal Varices
98.5%) and rule-in CSPH (specificity 97.1%). A recent One of the most relevant applications of elastometry is the
meta-analysis reported for SSM by TE a good identification of patients with gastroesophageal varices.

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Patients with ACLD require routine endoscopic surveil­ spared endoscopies without raising the rate of missed
lance in order to identify esophageal varices needing treat­ HRV. In a large cohort of almost 500 patients, this algo­
ment (VNT), reduce upper digestive bleeding incidence rithm allowed to safely increase the rate of spared endos­
and mortality. LSM is considered to have high sensitivity, copies to 43.8% (2% of HRV missed), as compared to
but medium/low specificity in predicting esophageal Baveno VI criteria alone (21.7%); the excellent perfor­
varices (EV) in several studies.62–66 A meta-analysis mance was then confirmed in a prospective multicenter
including about 3650 patients from 18 studies, showed cohort. Importantly, this combined model has been
that LSM has a sensitivity and a specificity of 87% and recently validated in a large prospective cohort of virally
53% for any varices, and 86% and 59% for VNT.67 suppressed HBV patients, producing excellent results in
Regarding SSM, Stefanescu et al68 analysed its perfor­ safely ruling-out HRV.31 Similar performances were
mance in chronic hepatitis patients; among cirrhotic group observed when combining Baveno VI criteria with SSM
population, SSM resulted higher in those with EV (63.69 assessed with Supersonic Shear Imaging.79
vs 47.48 kPa), with the best cut-off to detect EV of 52.5 In conclusion, non-invasive elastographic techniques
kPa. In 2012, Colecchia et al28 confirmed LSM and SSM are promising tools for EV prediction, and their combina­
as more accurate in predicting both CSPH and EV than tion will allow us to avoid unnecessary upper endoscopy
other NITs; moreover, they proposed a new combined in a considerable number of ACLD patients. However,
logistic model using together SSM and LSM to reduce which are the best criteria to apply in clinical practice is
indeterminate cases. still a matter of debate, and this topic will be hopefully
The last Baveno VI Consensus Workshop stated that in addressed during the upcoming Baveno VII consensus.
patients with ACLD, the prevalence of VNT in patients with
LSM < 20 kPa and platelet count is >150×109/L is low (<
5%), and endoscopic surveillance can be safely avoided in
Role of Elastography in the Prediction of
these patients.2 Since the postulation of these criteria in 2015, Liver-Related Events and Response to
many studies have validated their safety in clinical practice. Treatments
In a recent meta-analysis by Stafylidou et al69 including Prediction of Hepatic Decompensation and Mortality
about 9000 patients from 30 studies, Baveno VI criteria Liver and spleen stiffness correlate well with HVPG
proved to have a sensitivity of 0.97 and a specificity of 0.32 measurement and can identify patients with CSPH;
in predicting EV. Moreover, since Baveno VI criteria are therefore, it has been hypothesized that they can also
originally to be applied only in patients with viral chronic predict other complications driven by portal
liver disease, several efforts have been made for their valida­ hypertension.80 A meta-analysis81 has shown that an
tion in other etiologies (ie metabolic liver disease,65 chole­ increase of 1 kPa in LSM is associated with an increased
static liver disease,70 after HCV-eradication71). risk of hepatic decompensation [Relative risk (RR), 1.07;
Nevertheless, the number of spared upper endoscopies 95% CI, 1.03–1.11] and mortality (RR, 1.22; 95% CI,
by the application of Baveno VI criteria is relatively low 1.05–1.43). The proposed cut-offs for the prediction of
(15–25%), so different attempts have been made to modify risk of hepatic decompensation usually are >20-25
these criteria and increase the rate of spared endoscopies. kPa,82–85 the cut-off to rule-in CSPH according to
Augustin et al proposed to use LSM cutoff of 25 kPa and Baveno VI consensus.2 Interestingly, the accuracy of
PLT > 110 x 109/L72 (the Expanded Baveno VI), sparing LSM (0.837) for the prediction of any decompensation
up to 40–60% of upper endoscopies, as confirmed also by was not inferior to that of HVPG (0.815).82 Since LSM
other authors.73–75 However, a higher rate of missed EVs cut-offs are influenced by liver etiology, numerous stu­
has been reported, often over the safe threshold of dies have demonstrated that LSM is an independent
5%.76–78 This was confirmed also by a recent meta- predictor of decompensation and other liver-related
analysis,69 where the Expanded Baveno VI criteria showed events also in large cohorts of non-alcoholic fatty liver
superior specificity (51%) for HRV, but with an increased disease (NAFLD),86,87 primary biliary cholangitis,88,89
risk of missed HRVs (up to 10%). primary sclerosing cholangitis90,91 and other etiologies.92
More recently, a new combined model30 including SSM has also been validated as an accurate NIT able to
Baveno VI criteria and SSM (cut-off ≤ 46 kPa, assessed stratify for the risk of decompensation and overall mortal­
by TE), proved to be efficient in increasing the number of ity in ACLD patients.93–96 Colecchia et al93 showed that

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Dovepress Dajti et al

an SSM value of 54 kPa, evaluated by TE, could identify failure.4 A similar benefit in responders was recently
patients at lower risk of decompensation. Similarly, shown also for the prevention of the first decompensation
Takuma et al96 showed that SSM >3.25 and >3.43 m/s, event, mainly ascites, in the PREDESCI trial.14 With the
evaluated by p-SWE, accurately predicted decompensation broad administration of NSBB to all patients with CSPH,
and mortality, respectively. Recently, the 54 kPa SSM cut- it would become even more timely and relevant to identify
off was validated to predict decompensation after HCV hemodynamical responders, the patients that truly benefit
eradication with direct-acting antivirals.97 from this medical treatment, and to avoid exposure to
In conclusion, LSM and SSM are well-validated surro­ significant adverse effects of NSBB, which are not uncom­
gates of portal hypertension and can be used in everyday mon, in non-responders. To date, no NIT has substituted
clinical practice as prognostic markers, able to stratify for HVPG in this context. Only recently a seminal paper by
the risk of decompensation and liver-related events. Kim et al119 developed and validated a model including
SSM, evaluated by p-SWE, that could predict for the first
Prediction of Outcomes in Patients with
time hemodynamic response with excellent accuracy
Hepatocellular Carcinoma
(AUROC=0.848). A recent pilot study11 also demonstrated
Studies with HVPG have shown that not only the degree of
that ΔSSM after NSBB initiation, as evaluated by TE,
liver fibrosis but also that of portal hypertension can predict
showed excellent correlation with ΔHVPG (r= 0.784),
the risk of HCC development,10 confirming that key features
and SSM reduction ≥10% predicted HVPG response with
of portal hypertension, such as hyperdynamic circulation,
an AUROC of 0.973. These studies are truly preliminary,
liver hypoxia, and splanchnic neoangiogenesis, play an
but SSM could be a very promising tool for the prediction
important role in liver carcinogenesis.98,99 Similarly, LSM
of hemodynamic response and warrants further studies.
has been extensively shown as a valid NIT able to predict the
risk of primary HCC,100 in different etiologies of liver Prediction of Outcomes in Patients with Transjugular
disease87,101–103 and also after HCV eradication after DAA Intrahepatic Portosystemic Shunts
treatment.104 Jung et al previously reported that LSM could Patients with TIPS represent another setting in which monitor­
also predict late recurrence after liver surgery105,106 when ing with NITs can provide clinically relevant information.
liver disease severity is a major contributor to such Firstly, an increase in LSM has been shown to correlate with
complication.107 More recently, SSM was found to be the systemic inflammation and independently predict mortality in
only independent predictor of late recurrence in a proof-of- patients undergoing TIPS placement;120 however, no or little
concept study,108 confirming a major contribution of portal correlation has been found between changes in LSM and
hypertension in liver carcinogenesis. portal pressure gradient before and after TIPS.121,122 On the
Portal hypertension is also a major determinant of mor­ other hand, ΔSSM significantly correlated with changes in
bidity and mortality in patients undergoing hepatic portal pressure gradient after TIPS (r= 0.56–0.87),121–126 and
resection.109 Since CSPH is not to be considered an absolute an SSM increase during follow-up can accurately predict TIPS
contraindication to liver surgery,110,111 a correct stratification dysfunction (AUROC=0.81–0.87),121,124,125,127 suggesting
according to the severity of portal hypertension is mandatory that SSM could play a pivotal role in the non-invasive mon­
in this context. LSM has been consistently shown to accu­ itoring of TIPS patency and prediction of complications after
rately predict the incidence of post-hepatectomy liver failure its placement.
(PHLF)112–114 or overall complications after hepatectomy;115
interestingly, the accuracy of LSM was found not inferior to Limits of Liver and Spleen Elastography in
HVPG116 and superior to ICG-r15ʹ114 for this outcome. More the Prediction of Portal Hypertension and
recently, SSM has been proposed as a more accurate predic­
tor of PHLF development,117,118 however, the number of
Its Complications
The evidence supporting the use of elastography in the
patients included is limited and more studies are required.
prediction of fibrosis and portal hypertension is substantial
Prediction of Response to Non-Selective so that its role is now recognized in numerous guidelines and
Beta-Blockers these techniques are used routinely in the evaluation of
As mentioned above, both acute and chronic HVPG patients with chronic liver disease. However, the limits of
response to NSBB has been shown to correlate with the studies supporting this role should be acknowledged, in
a lower risk of variceal bleeding and medical prophylaxis order to be addressed and overcome by future research. The

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Hepatic Medicine: Evidence and Research 2021:13 31
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main limits of the above-mentioned papers are the retro­ Funding

spective nature and the inclusion of patients with mainly No grants or other financial support.
active viral hepatitis. Indeed, most of the studies were retro­
spective and lack of prospective validation in large multi­ Disclosure
center cohorts. The selection of patients was not always The authors declare that they have no conflicts of interest.
adequate, as patients with previous decompensation were
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