European Journal of Cardiovascular Medicine

Ranking as the sixth most common cancer and third leading cause of cancer-related deaths worldwide [1].A substantial burden of HCC falls upon developing countries such as India, where chronic hepatitis B and C infections and alcohol-induced liver disease remain prevalent [2]. Early detection is critical to improving survival rates; however, many patients are diagnosed at an advanced stage due to the silent nature of early HCC [3].

Imaging plays a pivotal role in both diagnosis and staging. Multiphase contrast-enhanced Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the cornerstones of non-invasive HCC diagnosis, especially under the Liver Imaging Reporting and Data System (LI-RADS) framework 4. While CT is widely available and cost-effective, MRI—particularly when enhanced with hepatobiliary-specific contrast agents—offers superior soft tissue characterization and has shown higher sensitivity in early lesion detection [5].

Several international studies have compared CT and MRI in various patient populations, revealing MRI to have higher sensitivity but variable specificity compared to CT [6, 7]. In a 13-year meta-analysis, MRI outperformed CT and ultrasound in both sensitivity and positive predictive value for HCC detection [8]. Similarly, prospective comparative studies in cirrhotic patients highlighted MRI’s superiority in detecting smaller lesions, which are often missed on CT[ 9].

However, despite promising data, no such head-to-head diagnostic performance study has been conducted in North India, particularly at a tertiary care centre like SMS Hospital, Jaipur. Furthermore, real-world data assessing combined modality utility (CT + MRI) remains underreported in the Indian context [10]. This study aims to fill that gap by prospectively comparing CT and MRI in the early detection and staging of HCC, leveraging a structured cohort over a one-year period.

Aims and Objectives

 Primary Objective

To compare the sensitivity, specificity, and diagnostic accuracy of CT versus MRI in the early detection of hepatocellular carcinoma.

 Secondary Objectives

1. To compare the effectiveness of CT and MRI in staging HCC, specifically for identifying vascular invasion, satellite nodules, and extrahepatic spread.
2. To evaluate the incremental diagnostic value when both CT and MRI are used in combination.
3. To assess the impact of lesion size (<2 cm vs. ≥2 cm) on detection sensitivity across both imaging modalities.

Study Design and Setting

This was a prospective diagnostic accuracy cohort study conducted at the Department of Radiodiagnosis, SMS Medical College and Hospital, Jaipur, India. The study spanned a 12-month duration from April 2024 to March 2025, following approval by the Institutional Ethics Committee

Study Population

A total of 120 adult patients (aged ≥18 years) with clinical suspicion or risk factors for hepatocellular carcinoma (e.g., cirrhosis, hepatitis B/C infection, elevated AFP) were consecutively enrolled from outpatient and inpatient referrals to the Radiology Department.

Inclusion Criteria

Patients were eligible for inclusion if they were aged 18 years or older and presented with clinical, radiological, or biochemical suspicion of hepatocellular carcinoma. Eligible participants were required to have undergone both contrast-enhanced CT and gadoxetic acid-enhanced MRI within a two-week interval. A definitive diagnosis of HCC was established either through histopathology or by applying the LI-RADS v2018 classification in conjunction with clinical follow-up.

Exclusion Criteria

Patients were excluded from the study if they had previously received treatment for hepatocellular carcinoma, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), or hepatic resection. Additional exclusion criteria included contraindications to iodinated or gadolinium-based contrast agents, such as significant renal dysfunction or documented hypersensitivity. Patients with incomplete imaging datasets or those who were lost to follow-up before a final diagnosis could be established were also excluded.

Imaging Protocols

Computed Tomography (CT)

All patients underwent triphasic contrast-enhanced CT scans using a 64-slice multidetector scanner (GE Revolution EVO). The protocol included:

• Non-contrast, arterial, portal venous, and delayed phases.
• Iohexol contrast at 1.5 mL/kg, injected at 3.5 mL/s.
• Scan delay: arterial phase at 25–30 s, portal phase at 60–70 s, delayed at 3–5 minutes.

Magnetic Resonance Imaging (MRI)

MRI was performed on a 1.5T system (Siemens Magnetom Aera) with a liver-specific protocol, including:

• T1W in-phase and out-of-phase, T2W, diffusion-weighted imaging (DWI).
• Gadoxetic acid (0.025 mmol/kg) used as the contrast agent.
• Arterial, portal, transitional, and hepatobiliary phases (20 minutes post-injection).

Two board-certified radiologists (blinded to the other modality and clinical details) independently reviewed CT and MRI scans. Imaging findings were categorized per LI-RADS v2018.

Reference Standard

The final diagnosis was based on:

• Histopathological analysis where available (surgical specimen or biopsy).
• In cases without histopathology, clinical-radiological diagnosis using AASLD guidelines and follow-up imaging at 3–6 months.

 Statistical Analysis

All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY) and R version 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria). Diagnostic performance metrics—sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy—were calculated for both CT and MRI modalities. Categorical data comparisons were conducted using the Chi-square (χ²) test, while McNemar’s test was applied to evaluate differences in paired proportions. Interobserver agreement between radiologists interpreting the imaging studies was assessed using Cohen’s Kappa statistic. Where relevant, effect sizes such as Cramer’s V (for χ² tests) and Cohen’s d (for mean differences) were reported. A p-value < 0.05 was considered statistically significant.

Fig.1 – Triple phase CECT abdomen shows isodense nodule in segment 4 of liver on non contrast images (A) with significant arterial enhancement on arterial phase(B) and washout on venous phase (C) consistent with diagnosis of hepatocellular carcinoma in the background of cirrhotic liver changes

Fig. 2-- Triple phase CEMRI abdomen shows heterogeneous arterial enhancing mass lesion in segment 4 of liver on arterial phase (A) with washout on venous and delayed phase (B and C) showing diffusion restriction in form of heterogeneous hyperintensity on DWI (b-800) (D) and corresponding hypointensity on ADC (E) consistent with diagnosis of hepatocellular carcinoma

Patient Demographics and Baseline Characteristics

A total of 120 patients were included in the final analysis. The mean age was 56.3 ± 10.1 years. The study cohort consisted predominantly of males (87 patients, 72.5%) compared to females (33 patients, 27.5%). Cirrhosis was present in 74.2% of patients, with HBV and HCV seropositivity observed in 34.2% and 24.2%, respectively. Alcoholic liver disease was identified in 30% of the cohort. Imaging revealed single lesions in 57.5% and multiple lesions in 42.5% of patients.

Table 1. Baseline Demographic and Clinical Characteristics (n = 120)

Lesion Characteristics

Across the cohort of 120 patients, a total of 174 hepatocellular carcinoma (HCC) lesions were identified. Of these, 61 lesions (35.1%) measured less than 2 cm in diameter, while the remaining 113 lesions (64.9%) were 2 cm or larger. Regarding the distribution pattern, 57.5% of patients presented with a single lesion, whereas 42.5% exhibited multifocal disease at the time of imaging.

Table 2. Lesion Characteristics in Study Cohort

Diagnostic Performance of CT and MRI

The diagnostic accuracy analysis included 160 lesion-level assessments, based on availability of definitive histopathology or robust clinical-radiological confirmation.

MRI outperformed CT across all diagnostic parameters. MRI demonstrated a sensitivity of 91.2%, significantly higher than CT's 79.6%, and a specificity of 87.2% compared to CT’s 83.0%. The positive predictive value (PPV) and negative predictive value (NPV) for MRI were 94.5% and 80.4%, respectively, while CT yielded a PPV of 91.8% and NPV of 62.9%. Overall diagnostic accuracy was 90.0% for MRI and 80.6% for CT.

Statistical comparison using McNemar’s test revealed a significant difference in detection sensitivity between CT and MRI (χ² = 9.21, df = 1, p = 0.002), indicating the superiority of MRI in lesion detection. The effect size calculated via Cramer’s V was 0.24, suggesting a moderate practical significance.

Table 3. Diagnostic Performance Metrics of CT and MRI (Lesion-Level, n = 160)

Figure 1. ROC Curve Comparison: CT vs. MRI for HCC Detection

Figure 1. Receiver Operating Characteristic (ROC) Curve Comparison of CT and MRI for Lesion-Level HCC Detection.
The ROC curves demonstrate the diagnostic performance of CT and MRI in detecting hepatocellular carcinoma (HCC) lesions (n = 160). MRI shows superior discriminative ability with an AUC of 0.93 compared to 0.84 for CT. The diagonal line represents the no-discrimination line. MRI achieved higher sensitivity and specificity across most thresholds, further supporting its role in early HCC detection.

 Impact of Lesion Size on Detection

To evaluate the effect of lesion size on detection performance, lesions were stratified into two categories: <2 cm (n = 61) and ≥2 cm (n = 113).

MRI detected 54 out of 61 small lesions (<2 cm), yielding a detection rate of 88.5%, whereas CT detected 41 out of 61 (67.2%). For larger lesions (≥2 cm), MRI identified 102 out of 113 (90.3%) and CT detected 82 (72.6%).

However, a Chi-square test of independence revealed that the difference in detection rates between CT and MRI across size categories was not statistically significant (χ² = 0.009, df = 1, p = 0.923). While MRI consistently outperformed CT numerically, this analysis suggests lesion size did not significantly influence the relative diagnostic performance between the modalities within this sample.

Table 4. Lesion Detection Rates by Lesion Size Category

Figure 2. Lesion Detection by Imaging Modality and Lesion

Figure 2. Lesion Detection by Imaging Modality and Lesion Size

This bar chart illustrates the number of lesions detected by CT and MRI stratified by lesion size. MRI consistently detected more lesions in both categories, particularly in the <2 cm group. However, as previously noted this difference did not reach statistical significance.

 Combined Modality Yield (CT + MRI)

When CT and MRI findings were analyzed together, a total of 86 lesions (53.8%) were detected by both modalities. Notably, 17 lesions (10.6%) were detected only by MRI, underscoring its added value in lesion visualization, particularly for subcentimeter or isovascular nodules.

 
Conversely, 4 lesions (2.5%) were detected only by CT, which were primarily hypervascular lesions with atypical features on MRI. A total of 7 lesions (4.4%) were missed by both modalities, which were later confirmed histologically, primarily due to their small size (<1 cm) or atypical enhancement patterns.

These results emphasize that while MRI alone provides higher sensitivity, a combined imaging strategy can yield improved diagnostic completeness, particularly in complex or borderline imaging cases.

Table 5. Detection Profile by Combined CT and MRI Modality

Figure 3. Venn Diagram of Lesions Detected by CT and MRI

Figure 3. Venn Diagram Illustrating Lesion Detection Overlap Between CT and MRI

The diagram shows the number of hepatocellular carcinoma (HCC) lesions detected by CT alone (n = 4), MRI alone (n = 17), and by both modalities (n = 86). MRI demonstrated greater standalone detection capability and contributed significantly to overall diagnostic yield when used in combination with CT.

Interobserver Agreement

Interobserver variability was assessed using Cohen’s Kappa statistic, comparing lesion-level categorizations (HCC present vs. absent) made independently by two board-certified radiologists for each imaging modality.

For CT, Cohen’s Kappa was 0.68, indicating substantial agreement. For MRI, Cohen’s Kappa was 0.78, indicating substantial-to-almost perfect agreement.

These results suggest that MRI not only provides higher diagnostic accuracy but also yields more consistent interobserver interpretation, potentially due to better contrast resolution and lesion conspicuity on hepatobiliary phase imaging.

Interpretation Scale (Landis & Koch):

- 0.61–0.80: Substantial agreement

- 0.81–1.00: Almost perfect agreement

Table 6. Interobserver Agreement for CT and MRI Interpretation

This prospective diagnostic accuracy study offers robust evidence on the comparative performance of contrast-enhanced CT and gadoxetic acid-enhanced MRI in diagnosing hepatocellular carcinoma (HCC). Conducted in a real-world tertiary care setting, our findings underscore the superior diagnostic capability of MRI, particularly in the early identification and accurate staging of HCC.

MRI demonstrated significantly higher sensitivity (91.2%) and specificity (87.2%) compared to CT (79.6% and 83.0%, respectively), with an overall diagnostic accuracy of 90.0% versus 80.6%. These findings are supported by the meta-analysis conducted by Lee et al. [11], which found consistently higher detection rates of HCC across LI-RADS categories using MRI. Similarly, Tang et al. [12] performed a systematic review affirming the evidence base for LI-RADS major features, concluding that MRI outperforms CT in lesion conspicuity and vascular characterization.

Lesion size remains a key determinant in diagnostic yield. In our study, MRI identified 88.5% of lesions <2 cm, while CT detected 67.2%, a trend echoed in the meta-analysis by Liang et al. [13], which highlighted a drop in CT sensitivity for sub-centimeter HCCs. Moura Cunha et al. [14] also reported MRI’s superior performance for smaller lesions, owing to hepatobiliary contrast enhancement and diffusion-weighted imaging.

In select patients, the integration of both imaging modalities enhanced diagnostic completeness. Seventeen lesions were exclusively detected by MRI, while four were seen only on CT. This complementary behavior aligns with findings from Hu et al. [15], who compared CEUS and CT/MRI LI-RADS and emphasized that some HCCs demonstrate atypical enhancement patterns best appreciated when both modalities are combined.

Our interobserver agreement analysis showed Cohen’s Kappa values of 0.68 for CT and 0.78 for MRI, consistent with the findings of Ehman et al. [16], who observed higher reader concordance for MRI-based LI-RADS assessments than for CT, particularly in early-stage or non-classical lesions.

However, both modalities failed to detect seven lesions later confirmed histologically. Such limitations are not unique; Sugimoto et al. [17] noted that even modified CEUS LI-RADS systems miss certain atypical HCCs. Additionally, Cunha et al. [18] and Wen et al. [19] emphasize the role of multimodal imaging, biopsy, or short-term follow-up in equivocal or high-risk scenarios.

The strengths of our study include prospective data collection, use of dual-radiologist consensus, histopathological or validated clinical endpoints, and rigorous statistical testing (McNemar’s test, Cramer’s V, and Cohen’s Kappa).

Limitations

This study was conducted at a single tertiary care center, which may limit generalizability to broader populations. While histopathological confirmation was obtained wherever feasible, some diagnoses were based on imaging and clinical follow-up, which could introduce verification bias. Additionally, the modest sample size, particularly in the subcentimeter lesion subgroup, may have underpowered certain statistical comparisons. Lastly, resource constraints limited dynamic contrast-enhanced MRI sequences in a subset of cases.

MRI outperformed CT in the early detection and staging of hepatocellular carcinoma, demonstrating higher sensitivity, specificity, and interobserver agreement. Its superiority was most evident for subcentimeter lesions and in diagnostic consistency. While CT remains a valuable initial modality, MRI should be preferred where available. A combined CT+MRI approach may be considered in diagnostically challenging cases to enhance lesion detection and staging accuracy.

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