Correlation of liver imaging and transient elastography among patients with hepatitis C at a safety net hospital

Abstract

BACKGROUND

Liver imaging and transient elastography (TE) are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus (HCV) infection. However, the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.

AIM

To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.

METHODS

We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019. We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging. Liver imaging findings (hepatic steatosis, increased echogenicity, cirrhosis, and chronic liver disease) were further evaluated for their diagnostic performance in detecting fibrosis (≥ F2, ≥ F3, ≥ F4) and steatosis (≥ S1, ≥ S2, ≥ S3).

RESULTS

Of 959 HCV patients who underwent TE, 651 had liver imaging. Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings (P = 0.0050), hepatic steatosis (P < 0.0001), and increased echogenicity (P < 0.0001). Higher liver stiffness measurement values were also noted in those with abnormal liver (P < 0.0001) and increased echogenicity (P = 0.0026). Steatosis severity correlated with hepatic steatosis (r = 0.195, P < 0.001) and increased echogenicity (r = 0.209, P < 0.001). For fibrosis detection, abnormal liver imaging had moderate sensitivity (81.7%) and specificity (70.4%) for cirrhosis (≥ F4), while cirrhosis on imaging had high specificity (99.2%) but low sensitivity (18.3%). Increased echogenicity showed high specificity (92.8%) but low sensitivity (20.9%) for steatosis detection.

CONCLUSION

Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity. Integrating TE with imaging may improve evaluation in patients with HCV.

Key Words: Transient elastography; Liver stiffness measurement; Controlled attenuation parameter; Hepatic steatosis; Hepatic fibrosis; Liver imaging; Chronic hepatitis C virus

Core Tip: Conventional liver imaging and transient elastography (TE) are commonly used to assess liver fibrosis and steatosis in individuals with hepatitis C virus. This study evaluates the diagnostic performance of imaging findings in detecting fibrosis and steatosis across different disease stages and their correlation with TE measurements. While imaging demonstrates high specificity for advanced liver disease, its limited sensitivity in earlier disease stages underscores the need for a multimodal approach. These findings help inform clinicians in resource-limited settings on the strengths and limitations of liver imaging when TE is unavailable.

INTRODUCTION

Liver imaging and transient elastography (TE) are both tools used to assess liver fibrosis and steatosis among people with liver disease, including those with hepatitis C virus (HCV) infection. Historically, a pretreatment evaluation of liver fibrosis in chronic hepatitis C with a liver biopsy was considered the gold standard[1]. However, given the invasive nature of this procedure, high costs for serial assessments, and potential complications, non-invasive methods have been adopted to estimate the degree of liver fibrosis and steatosis. Imaging such as ultrasound (US), computed topography (CT), and magnetic resonance imaging (MRI) have traditionally been used to assess morphological changes that could suggest cirrhosis or liver lesions to diagnose hepatocellular carcinoma but their ability to assess earlier stages of liver disease is unclear[1].

TE is a noninvasive technique that uses US shear waves to provide controlled attenuation parameter (CAP) to determine the degree of steatosis and liver stiffness measurement (LSM) to determine the degree of fibrosis[2,3]. TE has been validated in patients with chronic hepatitis C with sensitivity of 89% and 91% specificity for detecting advanced fibrosis[4]. Thus, TE has become rapidly implemented across the globe as a method for assessing liver fibrosis in chronic viral hepatitis[5-8]. While TE can accurately measure fibrosis and steatosis in lieu of liver biopsy, it is not well studied how TE findings correlate with findings on imaging modalities such as US, CT and MRI, especially in persons with HCV. Conventional US is the most common modality for qualitative assessment of hepatic steatosis. US has good sensitivity and specificity in detecting moderate to severe hepatic steatosis, but has limitations in detecting mild steatosis and differentiating between steatosis and fibrosis[9,10]. Similarly, CT and conventional MRI can be useful in quantifying more severe forms of hepatic steatosis and cirrhosis, but accurate staging of fibrosis and diagnosis of mild fibrosis is often challenging[11,12]. MR elastography (MRE) has shown some promise in accurately classifying fibrosis and steatosis in patients with metabolic associated steatotic liver disease but limited data exists on this imaging modality in patients with HCV[13,14]. Nonetheless, many patients with liver disease receive one or more of these imaging studies for diagnosis, treatment or monitoring. There is limited data to assess whether findings on liver imaging correspond to findings on TE. Given the limited availability of TE, liver imaging remains a widely accessible modality for assessing hepatic fibrosis and steatosis. Understanding the correlation between TE and imaging findings may help clinicians interpret imaging results in under resourced settings where TE is unavailable. The objective of this study was to investigate the correlation between steatosis (determined by CAP) and fibrosis (determined by LSM) and liver related findings on CT, MRI, and US in a population of patients with HCV at a safety net hospital.

MATERIALS AND METHODS

We conducted a retrospective cross-sectional analysis of all patients with HCV at Grady Memorial Hospital Liver Clinic in Atlanta, GA who underwent TE exams between January 1, 2018 and December 31, 2019. Grady Memorial Hospital is a safety-net health system with a high HCV prevalence that serves an urban population in Atlanta, Georgia. GHS is home to the Grady Liver Clinic, a primary care-based HCV specialty clinic that provides comprehensive HCV care and treatment. As part of the diagnostic process, patients undergo a pre-treatment TE exam to assess the severity of liver fibrosis and steatosis. We performed a parent study to examine the association between HCV, DM, liver fibrosis, and hepatic steatosis in this cohort of 959 patients[15]. For the current study, we further analyzed this cohort to determine the relationship between steatosis and fibrosis measurements by TE and findings of liver fibrosis and steatosis on liver imaging.

Our dataset included patients with a diagnosis of HCV, age > 18 years old, and with documented TE examination completed within the study period. Of the 959 patients with TE, 904 had valid CAP measurements and were included in steatosis severity analyses. Liver imaging was available for 651 patients which were used to assess radiologic liver abnormalities. A sub-group analysis was performed for patients with diabetes due to their heightened risk for steatotic liver disease. Patient charts in the electronic health record were reviewed for demographic data, liver imaging reports (US, CT, MRI), laboratory data, and medical comorbidities. Radiology reports were manually reviewed by a single research fellow (Hima Veeramachaneni) to assess for keywords including, “cirrhosis,” “hepatic steatosis,” “chronic liver disease,” “increased echogenicity” and “heterogenous/coarsened liver.” If any of these keywords were present, then the umbrella term “abnormal liver findings” was applied. Imaging findings were then compared to fibrosis (LSM) and steatosis (CAP) scores from TE measurements to assess correlation. For fibrosis staging, we used the following LSM cutoff values for patients with HCV: F0-F1: ≤ 7.0 kPa F2: > 7.0 kPa F3: ≥ 9.5 kPa F4 (cirrhosis): ≥ 12.0 kPa. For hepatic steatosis, CAP scores were classified as: S0 (No steatosis): 150-248 dB/minute S1 (mild steatosis): 248-260 dB/minute S2 (moderate steatosis): 260-280 dB/minute S3 (severe steatosis): > 280 dB/minute.

Statistical analysis

Correlations between LSM, CAP scores, and imaging findings were assessed using Spearman’s correlation coefficients. Differences in CAP scores across steatosis severity categories were evaluated using analysis of variance with pairwise comparisons to determine statistical significance. The diagnostic performance of imaging findings in detecting fibrosis and steatosis was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Positive likelihood ratio LR (+) and negative LR (-) were calculated to evaluate the ability of imaging findings to predict fibrosis (≥ F2, ≥ F3, ≥ F4) and steatosis (≥ S1, ≥ S2, ≥ S3) based on TE measurements. All statistical analyses were performed using SPSS software (version 29, SPSS Inc., Chicago, IL, United States). A P value of < 0.05 was considered statistically significant.

RESULTS

Demographic and clinical characteristics

The study cohort consisted of 959 patients with HCV infection (Table 1). The mean age of the participants was 64 years (SD = 9.81), with a male predominance (64.9%, n = 622). The majority were African American (81.3%, n = 780), followed by White (15.2%, n = 146), Hispanic (1.7%, n = 16), Asian (0.4%, n = 4), American Indian and Alaskan Native (0.3%, n = 3), and others (0.5%, n = 5). The average body weight of the participants was 80.44 kg (SD = 18.69), and the mean body mass index (BMI) was 27.13 kg/m² (SD = 5.89). In terms of BMI distribution, 38.1% of patients (n = 365) had a BMI of less than 25. Notably, approximately two-thirds of the patients (61.9%) had a BMI greater than 25.

Table 1 Demographics of patients with chronic hepatitis C virus with transient elastography, n (%).

Variables	Patients (n = 959)
Age (years), mean ± SD	64.05 ± 9.81
Gender
Male	622 (64.9)
Female	337 (35.1)
Race
African American	780 (81.3)
White	146 (15.2)
Hispanic	16 (1.7)
Asian	4 (0.4)
American Indian and Alaskan Native	3 (0.3)
BMI (kg/m²), mean ± SD	27.13 ± 5.89
BMI categories
< 25	365 (38.1)
25-30	326 (34)
30-35	163 (17)
35-40	79 (8.2)
> 40	26 (2.7)
Alcohol consumption	305 (49)
Comorbidities
CAD	89 (9.3)
Hypertension	669 (69.8)
Dyslipidemia	303 (31.6)
Obesity	202 (21.1)
Fibrosis score	6.9 (5.4-9.8)
CAP score, mean ± SD	222.86 ± 52.29
Steatosis severity1
S0	630 (69.7)
S1	56 (6.2)
S2	79 (8.7)
S3	139 (15.4)
Fibrosis assessment
F0-F1	500 (52.1)
F2	212 (22)
F3	71 (7.4)
F4	177 (18.5)
Labs
AST (IU/L)	30 (21-49)
ALT (IU/L)	16 (25-43)
HbA1c (%), mean ± SD	6.58 ± 1.92
Total bilirubin (mg/dL)	0.6 (0.4-0.8)
Platelet (103 /μL), mean ± SD	219.64 ± 84.68
Albumin (g/dL)	4.06 ± 0.45

¹Denominator for steatosis severity is 904 as 55 patients did not have complete controlled attenuation parameter scores.

BMI: Body mass index; CAD: Coronary artery disease; CAP: Controlled attenuation parameter; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HBA1c: Hemoglobin A1C.

TE and liver imaging findings

Liver fibrosis and steatosis measurements by TE showed a median fibrosis score (LSM) of 6.9 (interquartile range, interquartile range = 5.4-9.8) and a mean CAP score of 222.86 ± 52.29 dB/minute (Table 1). The fibrosis assessment based on all 959 patients who underwent TE, categorized 52.1% (n = 500) as having no fibrosis or mild fibrosis (F0-F1), 22% (n = 211) with moderate fibrosis (F2), 7.4% (n = 71) with advanced fibrosis (F3), and 18.5% (n = 177) with cirrhosis (F4) (Table 1). In terms of steatosis, among the 904 patients with valid CAP measurements, 630 (69.7%) had no steatosis (S0), 56 (6.2%) had mild (S1), 79 (8.7%) had moderate (S2), and 139 (15.4%) had severe steatosis (S3). In the 651 patients with liver imaging, cirrhosis was identified in 34 (5.2%), hepatic steatosis in 64 (9.8%), chronic liver disease in 176 (27%) and increased echogenicity in 75 (11.5%). 278 patients (42.7%) had one or more of the above findings and were thus characterized as having abnormal liver findings.

Correlation between liver imaging findings and steatosis by TE

LSM showed moderate to strong correlations with all imaging findings (Table 2). CAP scores had weaker associations with imaging findings, with the highest associations observed for hepatic steatosis (r = 0.21, P < 0.001) and increased echogenicity (r = 0.189, P < 0.001). Moreover, the analysis of variance test demonstrated significant differences in CAP scores across varying levels of steatosis severity, with higher CAP scores corresponding to increasing steatosis severity (P < 0.001 for all pairwise comparisons).

Table 2 Correlation of imaging findings with controlled attenuation parameter score and liver stiffness measurement.

Imaging findings	CAP score	LSM
Abnormal liver	r = 0.127, P < 0.001	r = 0.471, P < 0.001
Cirrhosis	r = -0.021, P = 0.527	r = 0.279, P < 0.001
Hepatic steatosis	r = 0.21, P < 0.001	r = 0.133, P < 0.001
Chronic liver disease	r = 0.03, P = 0.364	r = 0.42, P < 0.001
Increased echogenicity	r = 0.189, P < 0.001	r = 0.176, P < 0.001

CAP: Controlled attenuation parameter; LSM: Liver stiffness measurement.

Diagnostic performance of imaging findings in detecting fibrosis and steatosis

The diagnostic performance of imaging findings in detecting fibrosis and steatosis was assessed and summarized in Table 3 and Table 4. For fibrosis detection, abnormal liver appearance had a sensitivity of 81.7% and specificity of 70.4% for detecting cirrhosis (≥ F4), with a LR (+) of 2.76 and LR (-) of 0.26. Chronic liver disease on imaging showed moderate sensitivity (59.8%) and higher specificity (84.0%) for cirrhosis detection, with an LR (+) of 3.74. Cirrhosis on imaging exhibited high specificity (99.2%) but low sensitivity (18.3%), making it highly predictive for confirming cirrhosis when present but unreliable for ruling it out [LR (+) = 22.87, LR (-) = 0.82]. For steatosis detection, increased echogenicity had a sensitivity of 20.9% and specificity of 92.8%, yielding an LR (+) of 2.90 and LR (-) of 0.85, indicating a limited ability to detect steatosis. Hepatic steatosis on imaging had a sensitivity of 18.0% and specificity of 93.9%, with a PPV of 57.8% and an LR (+) of 2.95. Among all imaging findings, chronic liver disease had the highest PPV (84.1%) for fibrosis detection, while hepatic steatosis had the highest PPV (77.1%) for steatosis detection. However, negative predictive value were lower across all imaging findings, suggesting that imaging alone has a limited ability to exclude fibrosis and steatosis when findings are absent.

Table 3 Association between abnormal liver imaging and fibrosis staging in hepatitis C.

Variables	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	LR (+)	LR (-)
Abnormal liver finding
≥ F4	81.70	70.40	48.20	92.00	2.76	0.26
≥ F3	75.20	75.10	62.20	84.70	3.02	0.33
≥ F2	55.70	77.30	79.10	53.10	2.45	0.57
Cirrhosis
≥ F4	18.30	99.20	88.20	78.30	22.87	0.82
≥ F3	13.90	99.50	94.10	67.90	27.8	0.87
≥ F2	8.60	100.00	100.00	41.50	Inf	0.91
Hepatic steatosis
≥ F4	15.20	92.00	39.10	76.30	1.9	0.92
≥ F3	13.90	92.40	50.00	66.30	1.83	0.93
≥ F2	11.60	93.00	71.90	40.50	1.66	0.95
Suggestive of chronic liver disease
≥ F4	59.80	84.00	55.70	86.10	3.74	0.48
≥ F3	51.70	86.50	67.60	76.60	3.83	0.56
≥ F2	37.50	89.10	84.10	48.00	3.44	0.7
Increased echogenicity
≥ F4	17.10	90.30	37.30	76.40	1.76	0.92
≥ F3	18.30	92.20	56.00	67.40	2.35	0.89
≥ F2	14.20	92.60	74.70	41.10	1.92	0.93

PPV: Positive predictive value; NPV: Negative predictive value; LR: Likelihood ratio; Inf: Infinite.

Table 4 Association between abnormal liver imaging and steatosis staging in hepatitis C.

Variables	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	LR (+)	LR (-)
Abnormal liver finding
≥ S3	56.10	60.40	24.30	85.90	1.42	0.73
≥ S2	53.30	61.40	34.20	77.70	1.38	0.76
≥ S1	51.50	61.30	38.10	73.20	1.33	0.79
Cirrhosis
≥ S3	3.50	94.60	12.90	81.20	0.65	1.02
≥ S2	3.60	94.40	19.40	72.20	0.64	1.02
≥ S1	3.90	94.20	23.50	67.90	0.67	1.02
Hepatic steatosis
≥ S3	24.60	93.00	44.40	84.50	3.53	0.81
≥ S2	20.10	93.50	54.00	75.60	3.11	0.85
≥ S1	18.00	93.90	57.80	71.20	2.95	0.87
Suggestive of chronic liver disease
≥ S3	28.10	73.40	19.30	81.80	1.05	0.98
≥ S2	26.00	72.80	26.50	72.30	0.96	1.02
≥ S1	26.20	72.60	30.70	68.00	0.96	1.02
Increased echogenicity
≥ S3	24.60	91.30	38.90	84.20	2.81	0.83
≥ S2	23.10	92.60	54.20	76.10	3.13	0.83
≥ S1	20.90	92.80	57.30	71.70	2.9	0.85

PPV: Positive predictive value; NPV: Negative predictive value; LR: Likelihood ratio.

DISCUSSION

This study highlights the diagnostic utility of conventional imaging for detecting liver fibrosis and steatosis in patients with HCV and its correlation with TE findings. Our results indicate that while TE provides objective, quantitative measures of liver stiffness (LSM) and steatosis (CAP), the ability of imaging findings to detect fibrosis and steatosis varies by disease stage and imaging modality. Importantly, imaging demonstrated high specificity but limited sensitivity, making it more reliable for confirming advanced disease rather than detecting early-stage fibrosis or steatosis. Importantly, our findings underscore the strengths and limitations of each approach and offer insights into how they can complement one another in clinical practice.

Imaging findings as a diagnostic tool for fibrosis and steatosis in HCV

Our findings demonstrate that the diagnostic utility of imaging findings varies significantly depending on the stage of fibrosis and steatosis. While conventional imaging modalities exhibit high specificity for advanced disease stages (≥ F3 fibrosis and ≥ S2 steatosis), their sensitivity remains low, particularly in earlier stages, limiting their utility for early detection. The diagnostic performance of imaging findings for detecting fibrosis was stage-dependent. For cirrhosis (≥ F4), abnormal liver imaging demonstrated moderate sensitivity (81.7%) and specificity (70.4%), suggesting its utility for detecting advanced fibrosis. This makes it a useful screening tool for detecting cirrhosis, though it still lacks the precision of TE or biopsy confirmation. For ≥ F3 fibrosis, abnormal liver imaging showed moderate sensitivity (75.2%) and specificity (75.1%), while performance declined further for ≥ F2 fibrosis (sensitivity 55.7%, specificity 77.3%), indicating that imaging is less effective for detecting earlier fibrosis stages.

Similarly, imaging was more accurate for severe steatosis (≥ S3) than mild cases (≥ S1). Hepatic steatosis had high specificity (93.9%) but low sensitivity (18.0%) for ≥ S1 steatosis, meaning mild cases are often undetected. Sensitivity improved slightly for ≥ S3 steatosis (24.6%) while maintaining high specificity (93.0%), suggesting that imaging is more predictive as steatosis severity increases. This discrepancy likely reflects the fact that TE and imaging modalities are sensitive to different types of liver changes. For example, US and CT are better at detecting changes in liver structure and morphologic changes such as increased echogenicity or nodular liver surface, which are indirect indicators of fibrosis, while TE directly measures liver stiffness. Therefore, conventional imaging is most useful for confirming, not detecting, advanced fibrosis and steatosis. The moderate sensitivity and specificity of abnormal liver imaging for cirrhosis (81.7% and 70.4%) suggest it may serve as a screening tool where TE is unavailable, but its limitations in early-stage disease necessitate a multimodal approach integrating TE or liver biopsy.

Implications for clinical practice

The study underscores the complementary roles of TE and conventional imaging in the management of liver disease. TE offers a noninvasive and quantitative approach to fibrosis and steatosis staging, which is especially useful in settings without liver biopsy capabilities or when repeated assessments are needed. However, conventional imaging remains essential, especially when evaluating for complications such as hepatocellular carcinoma or identifying other liver lesions that TE cannot detect. Specialized imaging techniques, such as MRE, have shown promise in metabolic-associated steatotic liver disease by accurately identifying fibrosis and steatosis while offering valuable insights into liver-related complications. However, its clinical utility is limited by restricted accessibility. In settings where TE and MRE are unavailable, imaging findings such as echogenicity and morphologic liver changes may serve as useful indicators for steatosis and fibrosis, although they may not be as sensitive in detecting early-stage disease.

Limitations and future directions

There are limitations of this study that should be noted. The retrospective design introduces potential selection and reporting biases. Imaging findings were manually reviewed based on radiology reports, which could lead to variability in interpretation. Additionally, the cohort is predominantly African American from a single safety-net hospital, which may limit generalizability to other populations. In addition, this population all had HCV so this is not all inclusive of other conditions that can contribute to steatotic liver disease. Prospective studies with standardized imaging protocols and inclusion of advanced imaging techniques, such as MRE, could further illuminate the relationship between TE and imaging findings. Future research should investigate combining TE with advanced imaging techniques to improve diagnostic accuracy and explore how these tools affect long-term outcomes in HCV and other chronic liver diseases. It will also be important to assess the cost-effectiveness and accessibility of these technologies in different healthcare settings to ensure optimal liver disease management.

CONCLUSION

This study highlights the role of conventional imaging in liver fibrosis and steatosis assessment within safety-net HCV population. While TE remains a reliable and noninvasive tool for quantifying fibrosis and steatosis, imaging provides complementary structural information that enhances liver disease evaluation. Our findings demonstrate moderate correlations between TE and imaging findings; however, given the limited sensitivity of imaging for early fibrosis and steatosis, further studies are needed before imaging can be considered a reliable alternative in settings without TE. Ultimately, combining these modalities, guided by clinical context and resource availability, can lead to optimized liver disease management.

ACKNOWLEDGEMENTS

We would like to acknowledge the patients and staff at Grady Liver Clinic.