Splenic elastography in cirrhosis: A practical, non-invasive portal hypertension assessment from a Nigerian tertiary center

Abstract

BACKGROUND

Splenic stiffness measurement (SSM) via transient elastography is an emerging, non-invasive method for assessing portal hypertension and liver disease severity in cirrhosis. Its role is particularly relevant in low-resource settings where access to endoscopic services is limited.

AIM

To assess splenic stiffness patterns among cirrhotic patients using transient elastography and determine their relationship with liver disease severity.

METHODS

In a comparative cross-sectional study at a tertiary hospital in Katsina, Nigeria, 60 patients with clinically diagnosed liver cirrhosis and 60 age- and sex-matched healthy controls underwent SSM using transient elastography. Liver disease severity was classified using the Child-Pugh score. Data were analyzed using Mann-Whitney U, Kruskal-Wallis, and Spearman’s correlation tests.

RESULTS

Median SSM was significantly higher in cirrhotic patients compared with controls (56.8 kPa vs 17.9 kPa; P < 0.001). SSM increased progressively with worsening Child-Pugh class (A: 28.4 kPa; B: 56.7 kPa; C: 90.6 kPa; P < 0.001). SSM correlated positively with total bilirubin (r = 0.384; P = 0.002) and international normalized ratio (r = 0.441; P < 0.001), and negatively with serum albumin (r = -0.468; P < 0.001) and platelet count (r = -0.533; P < 0.001).

CONCLUSION

SSM correlates with liver disease severity and offers a practical, non-invasive alternative for assessing portal hypertension, potentially reducing reliance on endoscopy in resource-limited settings.

Key Words: Splenic stiffness; Transient elastography; Liver cirrhosis; Liver disease severity; Portal hypertension

Core Tip: Splenic stiffness measurement (SSM) by transient elastography is a promising, non-invasive proxy for portal hypertension in cirrhosis, especially where endoscopy access is limited. In this North-Western Nigerian cohort, SSM was significantly higher in cirrhotic patients and rose with advancing Child-Pugh class. Strong correlations emerged between SSM and indicators of liver dysfunction (bilirubin, international normalized ratio, albumin, platelets), supporting its utility as an objective severity marker. Implementing SSM could streamline risk stratification, monitor disease progression, and alleviate the burden on scarce endoscopic services in low-resource settings, offering a scalable tool for improving clinical decision-making.

INTRODUCTION

Liver cirrhosis is the end-stage of chronic liver disease, characterized by architectural distortion, fibrosis, and regenerative nodule formation[1]. Globally, it accounts for about two million deaths annually[2] with complications such as variceal bleeding contributing significantly to mortality[3]. Portal hypertension is a key pathophysiological hallmark of cirrhosis, defined as a portal pressure gradient exceeding 5 mmHg[4]. Clinically significant portal hypertension (CSPH) develops when the gradient exceeds 10 mmHg, at which point varices commonly form[5]. In low-resource regions like sub-Saharan Africa, hepatitis B virus infection is a leading cause of cirrhosis[6], and variceal bleeding remains a major cause of morbidity and mortality[3]. Upper gastrointestinal endoscopy is the gold standard for detecting varices[7], but its utility is limited in many low-resource settings due to high costs, lack of trained personnel, and limited infrastructure[8]. These barriers make routine endoscopic screening of all cirrhotic patients impractical.

Non-invasive tools for assessing portal hypertension include platelet count, spleen diameter, platelet count-to-spleen diameter ratio, and liver stiffness measurement (LSM)[9,10]. Recently, splenic stiffness measurement (SSM) using transient elastography has emerged as a promising surrogate marker[11]. Unlike LSM, which may plateau at higher stages of fibrosis, SSM reflects splenic congestion and fibrosis due to elevated portal pressures[11,12]. Studies in Europe and Asia have demonstrated that SSM correlates well with liver dysfunction and portal hypertension severity[11,13,14], but African data remain scarce.

This study aimed to characterize splenic stiffness patterns using transient elastography among cirrhotic patients in North-Western Nigeria and examine their relationship with liver disease severity, thereby evaluating its potential as a non-invasive tool for risk stratification in resource-limited settings.

MATERIALS AND METHODS

Study area

This study was conducted at the Federal Teaching Hospital Katsina, a 500-bed tertiary referral center in North-Western Nigeria. The Gastroenterology Unit is equipped with a FibroScan Expert 630 device (Echosens, Paris, France). Approximately 40 patients with cirrhosis are managed monthly, providing a consistent recruitment base.

Study design and participants

We conducted a comparative cross-sectional study from March 2024 to September 2024. Sixty adult patients (≥ 18 years) with liver cirrhosis and sixty age- and sex-matched healthy controls were recruited in a 1:1 ratio.

Inclusion criteria for case: Diagnosis of cirrhosis established by ≥ 2 of the following: (1) Clinical and/or biochemical features of chronic liver disease (e.g., ascites, variceal bleeding, hypoalbuminemia with reversed albumin/globulin ratio); (2) Imaging suggestive of cirrhosis (e.g., coarse echotexture, nodular surface); (3) Liver stiffness > 15 kPa on transient elastography in accordance with EASL 2021 Clinical Practice Guidelines[15]; and (4) Histological confirmation (METAVIR F4), where available.

Exclusion criteria for cases: (1) Age < 18 years; (2) Pregnancy; (3) Hepatocellular carcinoma (> 2 cm lesion with alpha-fetoprotein > 400 ng/mL); (4) Focal splenic lesions or massive ascites; (5) Participants with splenomegaly due to hematologic diseases, malaria, or congenital splenic disorders; and (6) Refusal to participate.

Inclusion criteria for controls: (1) No clinical or imaging evidence of chronic liver disease; and (2) Negative serology for hepatitis B surface antigen and anti-hepatitis C virus antibody.

Exclusion criteria for controls: (1) Patients with esophageal varices from non-cirrhotic portal hypertension; (2) Significant fluid overload from non-hepatic causes; (3) Obesity (body mass index ≥ 30 kg/m²); and (3) Participants with splenomegaly due to hematologic diseases, malaria, or congenital splenic disorders.

Clinical and laboratory assessment

All participants underwent detailed history-taking and physical examination. For cases, the severity of liver disease was assessed using the Child-Pugh classification, incorporating serum albumin, total bilirubin, international normalized ratio (INR), presence of ascites, and encephalopathy grade[16]. Blood samples were analyzed for: (1) Liver function tests (total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein); (2) Hematology (platelet count); (3) Coagulation profile (prothrombin time and INR); and (4) Viral serology (hepatitis B surface antigen, anti-hepatitis C virus antibody).

SSM

SSM was performed using transient elastography (FibroScan Expert 630, Echosens, Paris). The patient was positioned supine with slight right rotation to expose the posterolateral aspect of the left lower costal region. The spleen was identified via ultrasound guidance in the 7^th-9^th intercostal space along the posterior axillary line.

The Gastroenterology Unit comprises two consultant gastroenterologists and two fellows. One of the consultants had formal certification training in transient elastography (FibroScan^®) and supervised all procedures. At least ten valid measurements were taken with the M+ probe, ensuring an interquartile range (IQR) to median ratio ≤ 30% and a success rate ≥ 60%[17]. The median value was expressed in kPa.

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistics, version 30.0 (IBM Corp., Armonk, NY, United States). Continuous variables were assessed for normality using the Shapiro-Wilk test and summarized as mean ± SD or median with IQR, as appropriate. Categorical variables were presented as n (%). Comparisons between cirrhotic patients and healthy controls were conducted using the Mann-Whitney U test for non-normally distributed variables. Comparisons across Child-Pugh classes were evaluated using the Kruskal-Wallis test, with post hoc pairwise comparisons where applicable.

Associations between categorical variables were assessed using the χ² test or Fisher’s exact test, as appropriate. Correlations between splenic stiffness and laboratory parameters (platelet count, albumin, total bilirubin, and INR) were examined using Spearman’s rank correlation coefficient. Boxplots were used to illustrate group differences in splenic stiffness between cirrhotic patients and healthy controls, as well as across Child-Pugh classes. Scatterplots were used to depict correlations between splenic stiffness and key laboratory indices. All tests were two-tailed, and P < 0.05 was considered statistically significant.

Ethics

Ethical approval was obtained from the Human Research Ethics Committee of Federal Teaching Hospital Katsina (approval No. FTHKTNHREC.REG.24/06/22C/051). Written informed consent was obtained from all participants. The study adhered to the principles of the Declaration of Helsinki (2013 revision).

RESULTS

Participant characteristics

A total of 120 participants were enrolled: 60 patients with liver cirrhosis and 60 age- and sex-matched healthy controls. The overall mean age was 44.4 ± 12.0 years (range: 19-71), with males comprising 65% of the cohort (male-to-female ratio, 1.86:1). The age and sex distribution did not differ significantly between groups (P = 1.000; Table 1). Hepatitis B virus was the predominant etiology of cirrhosis (70%), followed by hepatitis C virus (10%). All patients reported herbal medication use, while none reported significant alcohol consumption.

Table 1 Demography of the participants, n (%).

Variable(s)	Liver disease category		Total	χ2	P value
	Control	Cases (cirrhosis)
Age of participants (in years)
≤ 30	9 (15.0)	9 (15.0)	18 (15.0)	0.000	1.000
31-40	10 (16.7)	10 (16.7)	20 (16.7)
41-50	19 (31.7)	19 (31.7)	38 (31.7)
51-60	14 (23.3)	14 (23.3)	28 (23.3)
≥ 61	8 (13.3)	8 (13.3)	16 (13.3)
Range	19-71	19-71	19-71
mean ± SD	44.32 ± 11.96	44.57 ± 12.11	44.44 ± 11.99
Gender of participants
Female	21 (35.0)	21 (35.0)	42 (35.0)	0.000	1.000
Male	39 (65.0)	39 (65.0)	78 (65.0)

SSM and laboratory parameters

Median SSM was markedly elevated in cirrhotic patients compared with controls [56.8 kPa (IQR: 36.4-88.9) vs 17.9 kPa (IQR: 14.2-20.6); P < 0.001; Table 2, Figure 1]. SSM values increased progressively with worsening liver disease severity: Child-Pugh A: 28.4 kPa; B: 56.7 kPa; and C: 90.6 kPa (P < 0.001 for trend; Figure 1B). Compared to controls, cirrhotic patients demonstrated significantly lower platelet counts and serum albumin levels, and higher total bilirubin and INR values (P < 0.001 for all comparisons; Table 2).

Figure 1 Boxplot. A: Splenic stiffness in healthy controls. Y-axis: Splenic stiffness (kPa) among control group. X-axis: Control. Legend: Boxplot showing the median and interquartile range of splenic stiffness among healthy controls; B: Splenic elastography cases by Child-Pugh score. Y-axis: Splenic stiffness (kPa) among cirrhotic patients. X-axis: Child–Pugh A|B|C. Legend: Median stiffness increases with advancing class (P < 0.001, Kruskal-Wallis test).

Table 2 Comparison of splenic stiffness measurement and key laboratory parameters between cirrhotic patients and controls, median (interquartile range)/mean ± SD.

Parameter	Cirrhotics (n = 60)	Controls (n = 60)	1P value
Splenic stiffness (kPa)	56.8 (36.4-88.9)	17.9 (14.2-20.6)	< 0.001
Platelet count (× 109/L)	85 (65-110)	220 (190-250)	< 0.001
Serum albumin (g/L)	30.2 ± 5.1	42.8 ± 3.6	< 0.001
Total bilirubin (μmol/L)	40.5 (22.3-78.6)	12.6 (9.8-15.4)	< 0.001
INR	1.6 ± 0.3	1.1 ± 0.1	< 0.001

¹Statistically significant.

INR: International normalized ratio.

Correlation between SSM and laboratory markers

Among cirrhotic patients, SSM showed strong negative correlations with platelet count (r = -0.53, P < 0.001; Figure 2A) and serum albumin (r = -0.47, P < 0.001; Figure 2B). Positive correlations were observed with total bilirubin (r = 0.38, P = 0.002; Figure 2C) and INR (r = 0.44, P < 0.001; Figure 2D). These findings indicate that splenic stiffness increases with worsening synthetic function and portal hypertension severity.

Figure 2 Scatter plots showing correlations in cirrhotic patients. A: Correlations between splenic stiffness measurement (SSM) and platelet count. X-axis: Platelet count (× 10⁹/L). Y-axis: Splenic stiffness (kPa). Legend: Spearman r = -0.53, P < 0.001; B: Correlations between SSM and serum albumin. X-axis: Serum albumin (g/L). Y-axis: Splenic stiffness (kPa). Legend: Spearman r = -0.47, P < 0.001; C: Correlations between SSM and total bilirubin. X-axis: Total bilirubin (μmol/L). Y-axis: Splenic stiffness (kPa). Legend: Spearman r = 0.38, P = 0.002; D: Correlations between SSM and international normalized ratio. X-axis: International normalized ratio. Y-axis: Splenic stiffness (kPa). Legend: Spearman r = 0.44, P < 0.001. INR: International normalized ratio; SSM: Splenic stiffness measurement.

DISCUSSION

Our study demonstrated a markedly elevated SSM in patients with liver cirrhosis compared to healthy controls, which increases progressively with worsening Child-Pugh class. Furthermore, SSM correlates significantly with key laboratory indicators of hepatic decompensation, including serum albumin, total bilirubin, INR, and platelet count. These findings underscore SSM’s potential as a non-invasive surrogate marker for portal hypertension and liver disease severity when used independently in low-resource settings.

Comparison with previous studies

Our results are consistent with studies from Europe and Asia, where SSM has shown strong associations with portal hypertension and cirrhosis severity[11,18-20]. Colecchia et al[11] reported that SSM was significantly higher in cirrhotic patients compared with controls and increased with worsening liver function, findings echoed in our cohort. Similarly, Siahaan et al[21] observed that SSM was superior to liver stiffness in predicting complications of portal hypertension.

African data remain limited. M Hussein et al[22] reported SSM among 50 Egyptians with cirrhosis; it was found to be significantly associated with the presence and grade of esophageal varices and correlated with thrombocytopenia, hypoalbuminemia, hyperbilirubinemia, and elevated INR, mirroring our findings. Our study expands this evidence base as the largest West African dataset to date, featuring a control group and a standardized elastography protocol.

While LSM is a well-validated marker of fibrosis and early portal hypertension, its sensitivity declines at advanced stages when hepatic fibrosis reaches a plateau. SSM, in contrast, reflects splenic congestion and fibrosis secondary to elevated portal pressure, providing a more direct index of portal hypertension. Comparative studies have shown SSM to outperform LSM in predicting CSPH and varices[11,18,21]. These findings support the potential complementary role of SSM in evaluating cirrhosis severity, especially in low-resource settings where invasive measurements are not feasible.

Several studies have proposed threshold values of SSM for identifying CSPH and esophageal varices. Colecchia et al[11] in 2012 reported a cut-off of 46 kPa for CSPH with an area under the receiver operating characteristic curve of 0.93, while Zykus et al[18] in 2015 found 47.6 kPa to predict the presence of esophageal varices in chronic liver disease. More recently, Liu et al[17] in 2023 identified 43.4 kPa as the optimal threshold for high-risk varices in cirrhotic patients using a spleen-dedicated transient elastography device. In our cohort, the median SSM among cirrhotic patients (56.8 kPa) and particularly in those with Child-Pugh C disease (90.6 kPa) exceeded these published cut-offs, suggesting that most of our participants likely had CSPH. Although the present study was not designed to determine a specific diagnostic threshold, these comparative data highlight the potential of SSM to serve as a practical, non-invasive indicator of portal hypertension severity in our setting. Future multicenter studies with larger cohorts are warranted to validate locally applicable cut-off values.

Pathophysiological considerations

The spleen enlarges and stiffens in cirrhosis due to a combination of passive congestion from elevated portal venous pressure, hyperplasia of the reticuloendothelial system, and fibrotic changes within the splenic parenchyma[23]. These structural alterations increase tissue elasticity modulus, measurable as higher kPa values on transient elastography. The progressive rise in SSM from Child-Pugh A to C in our study likely reflects worsening portal hypertension and splenic congestion with advancing disease.

The inverse correlation between SSM and platelet count aligns with the well-established link between hypersplenism and thrombocytopenia in cirrhosis[24]. Similarly, the negative association with serum albumin and positive association with bilirubin and INR reflect the intertwined pathophysiology of portal hypertension and hepatic synthetic dysfunction.

Clinical implications in low-resource settings

In many sub-Saharan African settings, endoscopic variceal screening is limited by availability, long wait times, and high out-of-pocket costs[8,25]. SSM offers a portable, rapid, and non-invasive alternative that could help triage patients for endoscopy, focusing scarce resources on those most likely to have advanced portal hypertension. Although the current study does not report variceal prediction cut-offs (reserved for a separate analysis), the strong correlation between SSM and markers of decompensation suggests that it could be integrated into clinical algorithms for cirrhosis management in low-resource contexts. Additionally, transient elastography requires minimal patient preparation, can be performed at the bedside or outpatient clinic, and yields immediate results. These features make it particularly appealing in rural and underserved areas where follow-up may be challenging.

Limitations

Cross-sectional design precludes assessment of longitudinal changes in SSM or its predictive value for outcomes such as bleeding or mortality. Single-center study may limit generalizability to broader populations. Measurement variability: While transient elastography is user-friendly, variability can occur, especially in patients with narrow intercostal spaces or high body mass index. Diagnostic confirmation: Although we included a well-matched control group, histological confirmation of cirrhosis was not available for all patients, introducing potential diagnostic misclassification. Findings in this study primarily reflects viral related etiology.

Future directions

Future multicenter prospective studies in Africa should evaluate SSM alongside other non-invasive markers to develop region-specific predictive algorithms. Integration of SSM into existing screening protocols could be tested for cost-effectiveness and impact on patient outcomes.

CONCLUSION

Splenic stiffness is significantly increased in patients with cirrhosis compared with healthy individuals and demonstrates a strong association with the severity of liver disease. In regions with limited endoscopic capacity, SSM provides a practical, non-invasive tool to inform clinical decision-making and optimize the allocation of endoscopic services. Broader implementation and rigorous validation of this approach have the potential to enhance liver disease assessment and improve resource utilization in low-resource settings.