Study of right liver lobe diameter to the serum albumin ratio as a marker of esophageal varices in patients with cirrhosis of liver

INTRODUCTION

Cirrhosis is the end stage for numerous etiologies of chronic liver diseases. It is defined by global hepatic fibrosis and nodular alteration of the hepatic architecture¹. India contributed to 18.3% of global deaths due to liver diseases in 2015.² With the rising prevalence of steatotic liver disease in Southeast Asia,³ Liver cirrhosis is expected to rise exponentially.

High portal pressures in cirrhosis cause the opening up of portosystemic collaterals leading to varices. The presence of esophageal varices (EVs) and variceal bleeding represents an important stage in the natural history of the condition. At diagnosis, EVs are seen in 40% of patients with compensated cirrhosis and in 60% of cases with decompensation.^4,5

The annual occurrence of initial variceal bleeding is approximately 4%.^6,7 The large size of varices and high intravariceal pressure are risk factors for bleeding EVs.^8,9 Annually, bleeding is seen in 1–2% of patients with no varices, 5% in cases with small varices, and 15–20% of patients with large varices.¹⁰ Development of newer varices is approximately 8% per year.¹¹ There is a 5% to 8% chance of death at 1 week and 20% at 6 weeks¹² after an acute episode of bleeding.

In patients with compensated cirrhosis and no varices, repeat endoscopy should be done once every 2-3 years, while small varices warrant endoscopy every 1-2 years and yearly screening in cirrhosis with decompensation. Although BAVENO VII¹³ consensus recommends that screening endoscopy be done if liver stiffness measurement (LSM) ≥20 kPa or thrombocyte count ≤150 × 10⁹/L, LSM has limited availability, and thrombocytopenia alone cannot be relied upon.

The rising incidence of cirrhosis and improved patient survival are putting significant pressure on endoscopists and creating financial strain on patients. This increasing demand for endoscopy services is challenging due to issues with accessibility, affordability, and medical risks. reliable, non-invasive markers are required to help detect EVs and potentially reduce the need for endoscopic procedures.

We aimed to identify a novel non-invasive parameter ie., liver size and serum albumin level ratio (RLL/Alb), that can become a potential marker of presence of EVs and their size.

MATERIAL AND METHODS

This study was conducted at a teaching institution located in Southern India. Institutional ethical committee clearance was obtained for the study.

RESULTS

A total of 150 patients were recruited for the study. The mean age among study subjects was 47.81 ± 8.99 years. There were 117 (78%) males and 33 (22%) females [Table 1]. Chronic alcohol intake was the most common etiology in 96 patients (64%); 36 patients (24%) had viral etiology, 9 (6%) were diagnosed to with an autoimmune cause, 4 (6%) with Wilson disease, and 3 (2%) were of unknown etiology [Figure 1].

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Figure 1:

Etiology of cirrhosis in the study population.

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Child-Turcotte-Pugh grades showed that 51 subjects (34%) belonged to grade A, 51 patients (34%) to grade B, and 48 patients(32%) to grade C. Sixty patients had grade 2 varices (40%), 37 patients had grade 1 (24.6%), 32 had no varices (21.3%), and 21 patients had grade 3 varices (14%) [Figure 2].

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Figure 2:

Esophageal Variceal grades in the study population (N=150).

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The mean measurement of the right liver lobe diameter was 10.82 ± 1.2 cm. The mean serum albumin level was 2.29 ± 0.85 mg/dL. The mean right liver lobe/albumin ratio was 5.22 ± 1.51 [Table 2 and Figure 3].

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Figure 3:

Right liver lobe diameter to serum albumin (RLL/Alb) ratio vs. Variceal grades (N=150).

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The mean right liver lobe diameter was 11.01 ± 1.3 cm in patients with no varices, 10.95 ± 1.18 cm in those with Grade 1 varices, 10.7 ± 1.12 cm for Grade 2 varices, and 10.6 ± 1.35 cm for Grade 3 varices. The difference was not statistically significant (p = 0.6866).

The mean albumin levels were 3.63 ± 0.74 in patients without varices, 2.22 ± 0.32 in those with Grade 1 varices, 1.94 ± 0.35 in patients with Grade 2 varices, and 1.14 ± 0.16 in those with Grade 3 varices. The differences were statistically significant (p < 0.001).

The mean RLL/Alb ratio in patients with no varices was 3.14 + 0.69, grade 1 was 4.99+ 0.57, grade 2 5.62+ 0.83, and grade 3 was 7.63 + 0.49. The correlation coefficient (r) was 0.8633 (positive correlation).

An additional analysis involved constructing a receiver operating characteristic (ROC) curve to know sensitivity and specificity. At an optimal cutoff value of 4.54, the sensitivity and specificity were 93.7% and 95.2%, respectively, with an area under the ROC curve (AUC) of 0.963, indicating statistical significance [Figure 4].

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Figure 4:

ROC curve to evaluate the RLL/Alb ratio as a marker for the presence of esophageal varices. ROC: Receiver operating characteristic curve, RLL/Alb: Right liver lobe diameter to serum albumin ratio.

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Discussion

Esophageal variceal bleeding, being the second most common decompensation, is a potentially lethal complication of liver cirrhosis. It imposes a heavy economic burden on health care as well as on patients.¹⁴ The mortality rate might be underestimated because many patients die before they can reach a hospital. Detecting EVs early and addressing them can help reduce complications. Screening of all patients using endoscopy is invasive and poses a significant financial burden.

Several studies have introduced laboratory and ultrasound-based methods for the non-invasive diagnosis of cirrhosis, including measurements like platelet count, splenomegaly, platelet count-to-splenic diameter ratio, serum albumin levels, and advanced Child-Pugh classification.

Our study was designed to test a novel marker, the right liver lobe diameter to serum albumin ratio, as a marker for the presence of EVs. This novel tool is derived by simple division of two parameters, which can be obtained from routine ultrasonography of the abdomen and serum albumin testing.

In the present study, the mean age of the study group was 47.81+ 8.99. The major age group in our study was between 40-60 years (78%), followed by < 40 years (18%) and > 60 years (4%). Our study comprised mostly male patients (78%), which was similar to a study published by Alempijevic et al.¹⁵ (2007).

The most common cause of cirrhosis in our study was chronic alcohol ingestion (64%), followed by viral causes (24%). An epidemiologic study published by Mondal et al.¹⁶ (2022) showed Hepatitis B to be the most common cause of cirrhosis. This difference might be explained by the difference in location and demography of the study sample.

Overall, the mean size of the right liver lobe was 10.8 ± 1.2 cm. The mean diameter of the right liver lobe in patients with no varices was 11.01 ± 1.3cm, grade 1 was 10.95 + 1.18 cm, grade 2 was 10.7+ 1.12 cm, and grade 3 was 10.6 ± 1.35 cm. The difference between the classes was not significant (p=0.6866).

In our study, the mean RLL/Albumin ratio was found to be high in grade 3 EVs (7.62 + 0.49), followed by grade 2 (5.62 + 0.83), grade 1 (4.99 + 0.57) and no varices (3.14 + 0.69). ANOVA test results indicated a significant difference (p < 0.001) between the mean values of the ratio across EV grades. With a cutoff ratio of 4.54, the sensitivity and specificity were determined to be 93.7% and 95.2%, respectively. This result may also be influenced by low variation within the groups, homogeneity of the sample, or potential overfitting to this specific group, indicating that larger studies are needed to confirm these findings.

A study by Alempijevic T et al.,¹⁵ (2007) reported a cutoff of 4.425 with a sensitivity of 83.1% and specificity of 73.9%.

Chowdhury et al.¹⁷ (2022) showed that The RLL/Alb ratio diagnosed the EVs using the cut-off value of 4.01 with 85.3% sensitivity and 68.8% specificity.

Study by Metwally AY et al.¹⁸ (2019) showed that at a cut-off of 3.7, the sensitivity, specificity, and accuracy of the RLL/Alb ratio to predict EVs were 95, 76.4, and 90%.

In our study, ANOVA test results indicated a significant difference between the mean ratio values across endoscopic grading levels (p = 0.001). The AUC for the ratio was 0.973, demonstrating statistical significance.

Esmat et al.,¹⁹ (2012) Akram et al.,²⁰ (2019) Ravali et al.²¹ (2023) have investigated the role of the Right liver lobe diameter/Alb ratio for noninvasively predicting the presence of EVs and got a positive correlation, showing it as a promising novel non-invasive tool. Although these markers cannot replace endoscopy, they carry significance in clinical practice, especially in a nation like ours where primary health care is the backbone of the health system.

Conclusion

In conclusion, the RLL/Alb serves as a novel, valuable non-invasive marker for predicting and grading EVs in cirrhotic patients. This approach can minimize the need for endoscopic procedures, reducing both the economic burden and patient risks associated with invasive screening. Given the scarcity of Indian studies focused on non-invasive markers like RLL/Alb, further regional research is essential to validate its effectiveness in diverse populations. Expanding the use of such markers could improve early diagnosis and tailored management in resource-limited settings.