Liver cirrhosis represents a significant global health burden, “characterized by progressive fibrosis and distortion of hepatic architecture that leads to portal hypertension and various systemic complications. While the hepatic manifestations of cirrhosis are well-documented, the disease’s impact on other organ systems, particularly the pulmonary system, has gained increasing attention in recent years.¹ The complex relationship between hepatic dysfunction and pulmonary abnormalities presents a critical area of investigation, as respiratory complications significantly influence the morbidity and mortality of cirrhotic patients. The concept of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) has been well established, demonstrating the direct impact of liver disease on pulmonary function. However, recent evidence suggests that pulmonary dysfunction in cirrhosis extends beyond these classical syndromes, with alterations in respiratory mechanics and gas exchange occurring even in the absence of clinically evident pulmonary disease.² Understanding these subtle changes through pulmonary function testing may provide valuable insights into disease progression and patient outcomes. Additionally, ascites can mechanically impair diaphragmatic function and reduce lung volumes, while muscle wasting associated with advanced liver disease may affect respiratory muscle strength and endurance.

Recent studies have suggested that alterations in pulmonary function may parallel the progression of liver disease, with more severe hepatic dysfunction associated with more significant impairment in respiratory parameters.³ The Child-Pugh classification and Model for End-Stage Liver Disease (MELD) score, widely used to assess liver disease severity, may show correlations with specific patterns of pulmonary dysfunction. The impact of cirrhosis on specific pulmonary function parameters has shown varying patterns across different studies. Some research has demonstrated predominant restrictive defects, particularly in patients with significant ascites, while others have reported obstructive patterns or mixed ventilatory abnormalities.⁴ The diffusing capacity for carbon monoxide (DLCO) has been consistently shown to be affected, suggesting impaired gas exchange as a standard feature of advanced liver disease.⁵ The clinical implications of understanding the relationship between liver cirrhosis severity and pulmonary function extend beyond diagnostic considerations. This knowledge could influence therapeutic strategies, such as the timing of therapeutic paracentesis, bronchodilators, or the implementation of pulmonary rehabilitation programs.” Moreover, pre-operative assessment of pulmonary function may be particularly relevant for patients being evaluated for liver transplantation.^6,7

This research aims to systematically evaluate the relationship between liver cirrhosis severity and pulmonary function test parameters to identify patterns that could enhance our understanding of hepatopulmonary interactions and improve patient care. By correlating PFT findings with established measures of liver disease severity, we hope to contribute to developing more comprehensive approaches to monitoring and managing patients with advanced liver disease.

This hospital-based cross-sectional study was conducted at the Department of General Medicine, Shri B M Patil Medical College and Research Centre, Vijayapura, Karnataka, India, from May 2023 to June 2024. A total of 65 patients were included with patients who are clinically or radiologically (USG) confirmed cases of cirrhosis of the liver and who are aged more than 18 years, irrespective of race and gender. “Patients with acute conditions such as sepsis, PTE, or ARDS, established lung disorders, such as COPD, bronchial asthma, old pulmonary Koch’s, bronchiectasis, ILD, cancer, and/or heart disorders and who suffer from illnesses including morbid obesity, neuromuscular diseases, or significant deformities of the chest wall or vertebral column that could affect their pulmonary function tests or result in hypoxemia and patients in poor general condition were excluded from the study.

Patient enrollment followed a systematic sampling approach, with all eligible patients invited to participate in the study after providing informed consent. Initial patient assessment was conducted on the day of admission. A structured interview was performed using a standardized questionnaire designed specifically for the study. In cases where patients could not respond, information was obtained from accompanying family members or other reliable sources. The questionnaire was designed to capture comprehensive demographic and clinical information. Detailed demographic information was collected, including name, age, sex, religion, and socioeconomic status (assessed using the modified Kuppuswamy scale). Lifestyle factors such as dietary habits, occupational stress levels, and personal habits were documented. A comprehensive clinical examination was performed on all participants, particularly concerning signs of liver disease and respiratory system involvement. The severity of liver cirrhosis was assessed using standardized criteria. Physical findings related to both hepatic and pulmonary systems were documented systematically.

A comprehensive panel of investigations was performed on all participants, including Liver function tests to assess hepatic synthetic function and injury, Viral markers (HIV, HCV, HBsAg) for etiological evaluation, Prothrombin time for coagulation assessment, Random blood sugar for metabolic evaluation. Imaging Studies: Participants underwent multiple imaging studies, including a chest X-ray to assess pulmonary pathology, Abdominal ultrasonography to confirm cirrhosis and assess for complications, and Electrocardiography to evaluate cardiac status. Pulmonary Function Assessment:              A detailed pulmonary function evaluation was conducted through spirometry testing for ventilatory function assessment and arterial blood gas analysis for gas exchange evaluation. All pulmonary function tests were performed following standard protocols and quality control measures.

All collected data was recorded in individual case record forms and transferred to a secure electronic database. Regular data auditing was performed to ensure completeness and accuracy of entries. Patient confidentiality was maintained throughout the study period.

Statistical analysis: SPSS version 21 was used to analyze the data after entering it into an Excel sheet. The findings were displayed both graphically and tabularly. For quantitative data, the mean, median, standard deviation, and ranges were computed. Frequencies and percentages were used to express the qualitative data.” Student t-test (Two-Tailed) was used to test the significance of the mean, and a P value <0.05 was considered significant.

The present study included a total of 65 patients. There was a statistically significant difference in age between the groups (p=0.019), with Group I (Child A) having the youngest patients (mean age 35.50 years), while Group II (Child B) had the oldest (mean age 46.52 years). Regarding gender distribution, males predominated in all groups, with Group II having one female patient, though this difference wasn’t statistically significant (p=0.415).

As expected, there was a highly significant difference between groups (p<0.001), with Group I having a mean score of 6.00, Group II having 8.29, and Group III having 11.03. This validates the proper stratification of patients into their respective Child-Pugh classes. There was a highly significant difference between groups (p<0.001), with progressively higher MELD scores as the Child-Pugh class worsened: Group I (10.67), Group II (13.76), and Group III (19.32). This demonstrates the correlation between these two liver disease severity classification systems

There was a highly significant difference in ascites severity across groups (p<0.001). Most patients in Group I (83.3%) had no ascites, while none in Group III were free of ascites. Moderate ascites were most common in Group III (50%), and gross ascites were present in 39.5% of Group III patients but not in Group I. This demonstrates that ascites severity increases with worsening liver function. Hepatomegaly showed a statistically significant difference (p=0.047) among groups, being most common in Group I (66.7%) and least common in Group II (19%). Splenomegaly and altered echo texture didn’t show statistically significant differences between groups, though splenomegaly was more prevalent in Groups II and III.

In our study population, there was a significant age difference between the three Child-Pugh groups (p=0.019), with Child A patient’s being the youngest (mean age 35.50 years) and Child B patients being the oldest (mean age 46.52 years). This finding differs somewhat from studies by Krowka et al., who reported a more linear relationship between age and cirrhosis severity, with progressively increasing age corresponding to worsening Child-Pugh class.⁸ “The predominance of male patients in our study (100% in Child A, 95.2% in Child B, and 100% in Child C) is consistent with the epidemiological pattern of liver cirrhosis observed globally, as reported by Mokdad et al., who found that cirrhosis affects men disproportionately in most populations worldwide.⁹

Our study’s arterial blood gas parameters showed a trend toward decreasing pH values with increasing severity of liver disease (Child A: 7.57, Child B: 7.42, Child C: 7.39), although this did not reach statistical significance (p=0.118). Similarly, PO2 values demonstrated a declining trend with increasing disease severity (Child A: 86.28 mmHg, Child B: 76.99 mmHg, Child C: 73.81 mmHg), though not statistically significant (p=0.353). These trends are consistent with findings by Mélot et al., who reported a progressive decrease in arterial oxygenation with worsening liver function in cirrhotic patients.¹⁰ The correlation analysis did not show significant correlations between Child-Pugh score and arterial blood gas parameters, including pH, PCO2, HCO3, PO2, and SO2. Similarly, we found no significant correlations between the MELD score and these parameters. This differs from studies by Lustik et al., who described metabolic acid-base disturbances in advanced cirrhosis due to impaired lactate clearance and renal dysfunction.¹¹ Contrast to this, the survey by Funk et al. demonstrated that acid-base derangements correlate with MELD score and can predict mortality in cirrhotic patients.¹² This discrepancy might be due to variations in patient populations or compensatory mechanisms present in our cohort.

Forced Vital Capacity (FVC) percentages showed a clear declining pattern with worsening liver function, both pre-bronchodilator (Child A: 76.17%, Child B: 68.21%, Child C: 58.81%, p=0.034) and post-bronchodilator (Child A: 78%, Child B: 70.4%, Child C: 59.71%, p=0.024). Similarly, Forced Expiratory Volume in 1 second (FEV1) percentages decreased significantly with increasing disease severity, both pre-bronchodilator (Child A: 80.5%, Child B: 67.7%, Child C: 59.9%, p=0.030) and post-bronchodilator (Child A: 83.3%, Child B: 70.8%, Child C: 60.6%, p=0.020). These findings are from the study by Krowka and Cortese, who reported reduced vital and total lung capacity in cirrhotic patients compared to controls.¹³ Similarly, Hourani et al. demonstrated reduced FVC and FEV1 in cirrhotic patients, with more pronounced reductions in those with more advanced disease.³ The mechanisms underlying these changes may include restricted diaphragmatic movement due to ascites, pleural effusions, muscle wasting, and respiratory muscle weakness secondary to malnutrition and electrolyte disturbances.

A key finding in our study was the significant negative correlation between Child-Pugh score and multiple pulmonary function parameters. We found statistically significant negative correlations for FVC (r=-0.505, p<0.001), FEV1 (r=-0.528, p<0.001), and FEF 25-75% (r=-0.440, p<0.001) in pre-bronchodilator measurements. Similarly, post-bronchodilator measurements showed significant negative correlations for FVC (r=-0.482, p<0.001), FEV1 (r=-0.521, p<0.001), and FEF 25-75% (r=-0.442, p<0.001). These findings strongly suggest that pulmonary function deteriorates in parallel with worsening liver function, with moderate strength correlations indicating a substantial relationship. The MELD score showed weaker but still significant negative correlations with FVC (r=-0.312, p=0.011) and FEV1 (r=-0.290, p=0.019) in pre-bronchodilator measurements and with FVC (r=-0.285, p=0.021) in post-bronchodilator measurements. The stronger correlations with the Child-Pugh score compared to the MELD score suggest that the Child-Pugh classification, which incorporates clinical parameters like ascites that directly affect pulmonary mechanics, may be more relevant for predicting pulmonary dysfunction than the MELD score, which is primarily based on laboratory parameters.

These findings are consistent with the study by Machicao et al., who found similar correlations between liver disease severity and pulmonary function abnormalities.¹⁴ The strength of our correlations underscores the close relationship between hepatic dysfunction and pulmonary impairment in cirrhosis. Our findings both align with and diverge from existing literature in several aspects. The progressive decline in FVC and FEV1 with worsening liver function is consistent with most previous studies. For instance, Vachiéry et al. reported similar findings in their cohort of cirrhotic patients, with FVC and FEV1 decreasing progressively from Child A to Child C.¹⁵ The strength of correlation between Child-Pugh score and pulmonary function parameters in our study is similar to that reported by Peng J et al.¹⁶ However, we found relatively weaker correlations between MELD score and pulmonary function parameters, which differs from some studies that have reported stronger correlations. This difference may be attributed to variations in study populations, methodologies, or the complex, multifactorial nature of pulmonary dysfunction in cirrhosis.”

Regarding arterial blood gases, our finding of decreasing PO2 with worsening liver function aligns with most previous studies. For example, Krowka et al. demonstrated a similar trend in their cohort of cirrhotic patients.⁸ However, we did not find significant correlations between liver disease severity and arterial blood gas parameters, contrasting with some previous studies. The relationship between ascites and pulmonary function has been more consistently reported. Our finding of increasing ascites severity with worsening liver function and concurrent deterioration of pulmonary function parameters aligns with the study by Chao et al., who demonstrated significant improvements in pulmonary function following large-volume paracentesis in cirrhotic patients with tense ascites.¹⁷

Strengths: The strength of study include its comprehensive data collection approach, structured questionnaire, clinical assessment of patients. The rigorous inclusion and exclusion criteria helped to eliminate the confounding variables. Additionally, study adopted a multimodal assessment approach incorporating the laboratory investigation, imaging studies and pulmonary function test. 

Limitation: The relatively small sample size, particularly in the Child A group (n=6), may have limited our ability to detect statistically significant differences or correlations. The cross-sectional design precludes establishing causality or temporal relationships between liver disease progression and pulmonary function changes. We did not assess smoking history in detail, which could be a significant confounder, particularly for the obstructive pattern observed. Future studies should control for smoking and other potential confounders like occupational exposures and concomitant respiratory diseases.

In conclusion, our study demonstrates that the severity of liver cirrhosis correlates with deterioration in pulmonary function, predominantly manifesting as a restrictive pattern in advanced disease. This understanding may guide clinicians in the comprehensive management of cirrhotic patients, emphasizing the importance of addressing pulmonary complications as part of the multisystem approach to this complex disorder.

Funding: Nil

Conflict of interest: Nil

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