Portal hypertension (PHT), defined as a pathological elevation of pressure in the portal venous system, is a major driver of morbidity and mortality in patients with chronic liver disease [1]. The clinical manifestations of PHT, including gastroesophageal varices with a risk of life-threatening hemorrhage, ascites, and splenomegaly, pose significant management challenges [2]. The underlying etiology of PHT can be broadly classified based on the site of vascular obstruction relative to the hepatic sinusoid, with the most common cause globally being liver cirrhosis, leading to sinusoidal and post-sinusoidal PHT, termed cirrhotic portal hypertension (CPH) [3].

However, a significant proportion of cases, particularly in developing countries like India, are due to non-cirrhotic causes (NCPH) [4]. This heterogeneous group includes pre-sinusoidal conditions such as extrahepatic portal venous obstruction (EHPVO), often a sequel of neonatal umbilical sepsis, and non-cirrhotic portal fibrosis (NCPF), an idiopathic condition characterized by periportal fibrosis without disruption of the liver architecture [5]. A key differentiating feature is that patients with NCPH typically have preserved hepatocellular function, leading to a better long-term prognosis compared to those with CPH, provided that variceal bleeding is effectively managed [3].

Accurate etiological diagnosis is therefore crucial for prognostication and therapeutic decision-making. While liver biopsy remains the gold standard for diagnosing cirrhosis, it is an invasive procedure with associated risks. Color Doppler ultrasonography has emerged as a valuable non-invasive tool for evaluating the portal venous system.

It allows for the direct visualization of vascular anatomy and provides quantitative hemodynamic data, including blood flow velocity, vessel diameter, flow volume, and arterial resistance indices [6, 7]. These parameters can reflect the underlying pathophysiological changes, such as increased intrahepatic resistance in cirrhosis or the development of a portal cavernoma in EHPVO.

Despite the known utility of Doppler ultrasound, there is a relative paucity of robust, prospective comparative data characterizing the full spectrum of hemodynamic changes between CPH and NCPH, especially from regions where NCPH is endemic. Tribal populations in India, for example, may have a unique exposure profile, including environmental or herbal toxins, and different healthcare access patterns, potentially influencing the etiological mix of PHT [8]. Differentiating CPH from NCPF in such settings without resorting to invasive tests is a clinically relevant challenge [9]. Establishing clear, non-invasive hemodynamic discriminators could significantly impact patient management in these resource-constrained environments.

Therefore, the aim of this prospective study was to perform a comparative analysis of portal hemodynamic parameters measured by Doppler ultrasonography in a well-characterized cohort of patients with cirrhotic versus non-cirrhotic portal hypertension from a tribal region of Maharashtra, India, to identify reliable distinguishing features.

Study Design and Setting

This prospective, comparative, observational study was conducted at the Departments of Gastroenterology and Radiology of a tertiary referral hospital that provides care to a large tribal population in Maharashtra, India. The study was conducted over a 12-month enrollment period from March 2022 to March 2023.

Study Population

A total of 180 consecutive adult patients presenting with clinical and/or radiological evidence of portal hypertension were enrolled. Patients were prospectively categorized into two groups: CPH and NCPH.

Inclusion Criteria:

1. Age > 18 years.
2. Evidence of portal hypertension (esophageal varices on endoscopy and/or splenomegaly >13 cm with dilated portal vein >13 mm on ultrasound).
3. A definitive etiological classification as either CPH or NCPH.

Exclusion Criteria:

1. Budd-Chiari syndrome or any cause of post-hepatic PHT.
2. Presence of hepatocellular carcinoma or other splanchnic malignancy.
3. Active variceal hemorrhage at the time of the scan.
4. Previous portosystemic shunt surgery, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation.
5. Acute-on-chronic liver failure.

Group Allocation

• CPH Group: Diagnosis was based on clinical signs of chronic liver disease, abnormal liver synthetic function (low albumin, high INR), and/or imaging findings suggestive of cirrhosis (nodular liver surface, coarse echotexture, signs of volume redistribution).
• NCPH Group: Diagnosis was based on evidence of portal hypertension with preserved liver synthetic function, patent hepatic veins, and absence of typical cirrhotic features on imaging. This group included patients with EHPVO (diagnosed by the presence of a portal cavernoma on imaging) and NCPF (diagnosed based on characteristic features after excluding other causes).

Doppler Ultrasound Protocol

All examinations were performed by one of two senior radiologists (with >10 years of experience) blinded to the patient's specific group allocation, using a high-end ultrasound machine (Philips Affiniti 70) with a 2-5 MHz curvilinear transducer. Patients were required to fast for at least 6 hours prior to the examination.
The following parameters were measured in a standardized manner:

• Portal Vein Diameter (PVD): Measured in quiet respiration at the point where the portal vein crosses the inferior vena cava.
• Time-Averaged Mean Portal Vein Velocity (PVV): Measured in the main portal vein with the Doppler sample volume covering at least two-thirds of the vessel lumen and an angle of insonation kept below 60°.
• Hepatic Artery Resistive Index (HA-RI) and Splenic Artery Resistive Index (SA-RI): Measured from a segmental hepatic artery in the right liver lobe and the splenic artery at the splenic hilum, respectively. RI was calculated as (Peak Systolic Velocity – End Diastolic Velocity) / Peak Systolic Velocity.
• Portal Vein Congestion Index (CI): Calculated using the formula: CI = (Portal Vein Cross-Sectional Area [cm²]) / (Mean Portal Vein Velocity [cm/s]).

 Statistical Analysis

All data were analyzed using SPSS version 25.0 (IBM Corp.). Continuous data were expressed as mean ± standard deviation (SD) and compared between the two groups using an independent samples t-test or Mann-Whitney U test, as appropriate, after checking for normality. Categorical data were expressed as frequencies and percentages and compared using the Chi-square test or Fisher’s exact test. A Receiver Operating Characteristic (ROC) curve analysis was performed to determine the diagnostic utility of key hemodynamic parameters in differentiating CPH from NCPH. A p-value < 0.05 was considered statistically significant.

Baseline Characteristics

A total of 180 patients were included in the final analysis, with 92 patients in the CPH group and 88 patients in the NCPH group. Within the NCPH group, 65 patients (73.9%) had EHPVO and 23 (26.1%) had NCPF. The demographic and clinical characteristics are summarized in Table 1. Patients in the NCPH group were significantly younger than those in the CPH group (38.5 ± 12.1 vs. 54.2 ± 9.8 years, p<0.001). As expected, patients with CPH had significantly impaired liver function, with lower serum albumin and higher bilirubin and INR values. Massive splenomegaly (longitudinal diameter >18 cm) was more common in the NCPH group (51.1% vs. 29.3%, p=0.003).

Table 1. Demographic and Baseline Clinical Characteristics

Comparison of Portal Hemodynamic Parameters

The results of the comparative hemodynamic analysis are presented in Table 2. The PVD was significantly larger in the NCPH group. The most striking differences were observed in the velocity and resistance indices. The mean PVV in the CPH group was significantly lower than in the NCPH group (11.8 cm/s vs. 15.6 cm/s, p<0.001). This resulted in a significantly higher portal vein CI in the CPH group, indicating greater congestion.

The HA-RI was markedly elevated in the CPH group (0.79 ± 0.06), consistent with increased intrahepatic resistance, whereas it remained in the normal range in the NCPH group (0.65 ± 0.07, p<0.001). The SA-RI was also higher in the CPH group, though the difference was less pronounced than for the HA-RI.

Table 2. Comparison of Doppler Hemodynamic Parameters

Diagnostic Performance of Hemodynamic Parameters

ROC curve analysis was performed to assess the ability of the most discriminant parameters—PVV, CI, and HA-RI—to differentiate CPH from NCPH. As shown in Table 3, HA-RI demonstrated the highest diagnostic accuracy, with an Area Under the Curve (AUC) of 0.94 (95% CI: 0.90-0.98). An optimal cut-off value for HA-RI of >0.72 yielded a sensitivity of 90.2% and a specificity of 88.6% for identifying patients with CPH. The CI also showed good diagnostic utility with an AUC of 0.81.

Table 3. Diagnostic Performance of Key Doppler Parameters for Differentiating CPH from NCPH

This prospective, comparative study conducted in a unique tribal population provides clear evidence that cirrhotic and non-cirrhotic portal hypertension are characterized by distinct and measurable hemodynamic profiles on Doppler ultrasonography. Our principal finding is that patients with CPH exhibit significantly lower portal vein velocity, a higher congestion index, and, most importantly, a markedly elevated hepatic artery resistive index compared to patients with NCPH. The HA-RI, in particular, emerged as a powerful non-invasive discriminator between the two entities.

The observed hemodynamic differences are well-explained by the underlying pathophysiology. In CPH, the primary abnormality is a profound increase in intrahepatic vascular resistance due to architectural distortion, fibrosis, and sinusoidal endothelial dysfunction [10]. This fixed and dynamic resistance impedes portal inflow, leading to a reduction in portal vein velocity and a consequent stasis or "congestion," which is reflected by a higher CI. Our finding of a mean PVV of 11.8 cm/s in the CPH group aligns with previous studies that identify low portal flow velocity as a hallmark of advanced cirrhosis [11].

Conversely, the elevated HA-RI in our CPH group is a critical finding. It reflects the "hepatic arterial buffer response," a physiological mechanism where hepatic arterial flow increases to compensate for reduced portal venous inflow [12]. In the rigid, high-resistance cirrhotic liver, this increased arterial flow and downstream obstruction result in a high-resistance waveform, elevating the RI. The high accuracy of an HA-RI >0.72 in our study (AUC 0.94) for identifying CPH strongly supports its use as a key diagnostic marker, corroborating findings from other cohorts [13].

In contrast, patients with NCPH, primarily EHPVO and NCPF in our cohort, have the site of obstruction at the pre-sinusoidal level. The liver parenchyma itself remains relatively compliant with preserved architecture [9]. Consequently, intrahepatic vascular resistance is not significantly increased, explaining the normal HA-RI (mean 0.65) we observed. While portal venous inflow is obstructed proximally, the liver maintains some degree of portal perfusion via the development of a portal cavernoma and other collaterals, which can result in relatively preserved or even variable portal vein velocities, as seen in our NCPH group (mean 15.6 cm/s) [14]. The larger PVD and more frequent massive splenomegaly in the NCPH group likely reflect the long-standing nature of high-volume, high-pressure pre-hepatic obstruction in a younger population with preserved liver compliance.

The clinical implications of these findings are substantial, especially for the population studied. In resource-limited settings, such as the tribal areas of India, access to advanced diagnostics like liver biopsy or hepatic venous pressure gradient (HVPG) measurement is often limited. The ability to differentiate CPH from NCPH using a widely available, non-invasive, and relatively inexpensive tool like Doppler ultrasound is invaluable [15]. This distinction is prognostically vital: a young patient with NCPH and preserved liver function has a near-normal life expectancy if variceal bleeding is controlled, often with shunt surgery. In contrast, a patient with CPH has a much poorer prognosis dictated by progressive liver failure, and management is centered on medical therapy, endoscopy, and eventual consideration for liver transplantation [16]. Our data provides a strong, evidence-based rationale for incorporating parameters like HA-RI into the routine diagnostic algorithm in these regions.

Our study's strengths include its prospective design, the inclusion of a well-defined and clinically relevant patient population from an understudied region, and the use of a standardized, blinded ultrasound protocol. However, we acknowledge certain limitations. First, this is a single-center study, which may affect the generalizability of our cut-off values. Second, Doppler ultrasound is known to be operator-dependent, although we sought to minimize this with experienced radiologists and a standardized protocol. Third, the "gold standard" of liver biopsy was not performed in all patients for ethical and practical reasons, and categorization was based on a composite of clinical and non-invasive findings.

In conclusion, this study demonstrates that cirrhotic and non-cirrhotic portal hypertension have distinct hemodynamic signatures on Doppler ultrasonography. A combination of low portal vein velocity, high congestion index, and particularly a high hepatic artery resistive index (HA-RI > 0.72) are reliable indicators of cirrhotic portal hypertension. These non-invasive parameters provide valuable diagnostic information that can help differentiate the etiology of portal hypertension, thereby guiding appropriate prognostic counseling and management strategies, especially in resource-constrained clinical environments.

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