Chronic liver disease (CLD) is a global health concern, characterized by the progressive deterioration of liver function due to various etiologies, such as chronic viral hepatitis, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD). ^[1] The progression of CLD often leads to cirrhosis, a    condition    where    liver    architecture    is extensively damaged, resulting in complications such  as portal  hypertension,  ascites,  and  hepatic  encephalopathy (HE). ^[2]    Hepatic    encephalopathy,    in    particular,    is    a Significant neuropsychiatric complication associated with liver failure, manifesting as a spectrum of cognitive dysfunction ranging from subtle changes in mental state to deep coma. ^[3]

While  hepatic  encephalopathy  is  traditionally  linked  to elevated   ammonia   levels,   recent   studies   suggest   that metabolic     abnormalities,     including     altered     purine metabolism and changes in serum uric acid (SUA) levels, may  also  play  a  role  in  its  pathophysiology. ^[4]  Uric acid is the final breakdown product of purine metabolism, and its serum levels are regulated by the liver and kidneys. In the context of liver dysfunction, impaired hepatic metabolism and   renal   insufficiency   often   lead   to   hyperuricemia. ^[5] However,   the   exact   role   of   serum   uric   acid   in   the progression of CLD and its potential association with hepatic    encephalopathy    remain    areas    of    ongoing research. ^[6]

Liver function tests (LFTs) are routinely used to evaluate the functional state of the liver, providing insights into the degree of liver damage and synthetic failure. ^[7] Parameters such as serum bilirubin, liver enzymes (ALT, AST, ALP), albumin, and the international normalized ratio (INR) offer valuable information about liver health.  However, the relationship    between    serum    uric    acid    and    these conventional LFT parameters in patients with CLD has not been thoroughly explored.  ^[9]

Understanding  the  connection between  serum  uric  acid  levels  and  liver  function  may offer new insights into the metabolic changes occurring in CLD and provide additional tools for assessing the severity of liver disease and the risk of complications like hepatic encephalopathy. ^[9] In this study, we aim to investigate the serum uric acid levels in patients with chronic liver disease and assess their correlation with the presence and severity of  hepatic  encephalopathy.  Additionally, we will explore the relationship between serum uricacid levels and various LFT parameters to better understand its potential role as a marker of disease severity.^[10]

This is a Prospective, Cross-sectional study and Observational study was conducted in the Department of General Medicine and OBGY, JIIU’s Indian Institute of Medical Science and Research. After approval from institutional ethical committee, this cross-sectional study was carried out for 18 months and 150 adult patients aged >18 years of either gender who were diagnosed with Chronic liver disease on the basis of clinical, radiological and biochemical investigation presenting to the OPD of Department of General Medicine and OBGY were included. Informed written consent was obtained from all patients satisfying the inclusion criteria after explaining the study protocol in detail.

Inclusion Criteria

Patients more than 18 years of age and diagnosed with Chronic liver disease on the basis of clinical, radiological and biochemical investigation

Exclusion Criteria

Patients having conditions which significantly alter uric acid level [e.g. patient of known malignancy (leukemias and lymphomas), gout, chronic kidney disease, on chemotherapy, patient on drugs affecting level of uric acid and with recent surgery and trauma] were excluded.

All patients coming to the emergency department and general medicine outpatient department were screened, and those fulfilling inclusion and exclusion criteria were enrolled in the study. Patients who left against medical advice were excluded from the study. All the patients and attendants were explained regarding this study, and those consenting were enrolled in the study. All patients were thoroughly investigated and all relevant personal and family history was recorded and detailed clinical examination was done.

Blood samples were collected for all enrolled subjects and evaluated for hemoglobin, total leukocyte count, platelet count, prothrombin time, serum concentration of bilirubin (total and conjugated), serum albumin, serum aspartate aminotransferase (AST/SGOT), and alanine transaminase (ALT/SGPT), and a modified Child–Pugh Score was be calculated.

Statistical Analysis

The collected data were entered into a Microsoft Excel Sheet. Tables were generated using Microsoft Word and Microsoft Excel version 2010. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) IBM version 18.0. The categorical variables were expressed as percentages, frequency, and proportions and compared using Pearson's Chi-square test or Fisher's exact test, as appropriate. A p ≤ 0.05 was considered statistically significant.

The present study was conducted on 150 patients. The age distribution ranged between 20 and 80 years. The mean age of the patients was 52.3 ± 11.4. In the present study, out of the 150 patients, 105 (70%) were males and 45 (30%) were females with chronic liver disease of various causes, diagnosed clinically and substantiated by imaging studies.

Table 1: Baseline Characteristics of the Study Population

Table 2: Cause of Chronic Liver Disease

In more than half of the patients, i.e., in 79 (52.7%) patients, alcohol was identified as a major cause of chronic liver disease, followed by Hepatitis B in 34 (22.7%) patients. Other causes accounted for chronic liver disease in 35 (23.3%) patients, with one case each of Wilson’s disease and autoimmune disease as a cause of chronic liver disease.

Table 3: Distribution of the participants based on Child Pugh Score

Table 4: Correlation of Serum Uric acid level with Child Pugh Score

Table 5: Serum Uric Acid Levels in CLD With and Without Hepatic Encephalopathy

Table 6: Correlation of Serum Uric Acid with LFT Parameters

Table 7: Distribution of Serum Uric Acid Levels

Our study aimed to evaluate the relationship between serum uric acid levels and the severity of chronic liver disease, hepatic encephalopathy, and LFT parameters. The findings highlight a significant association between elevated serum uric acid and worsening liver function.

We observed that serum uric acid levels increased with higher Child-Pugh scores, indicating more severe liver disease. Patients in Child-Pugh Class C had the highest uric acid levels, with a statistically significant p-value of 0.010. These findings align with studies by Yoon et al. (2018) and Wang et al. (2020), which demonstrated a positive correlation between serum uric acid and liver disease severity. ^[11,12] The proposed mechanism suggests that impaired liver function leads to decreased renal clearance of uric acid, contributing to hyperuricemia. ^[13]

Patients with hepatic encephalopathy (HE) had significantly higher serum uric acid levels compared to those without HE. The mean uric acid levels were 5.1 ± 0.9 mg/dL in HE Grades I-II and 5.9 ± 1.1 mg/dL in HE Grades III-IV (p < 0.001). This suggests that uric acid might serve as an indirect marker of worsening hepatic function and neuroinflammation. Similar trends were reported by Chen et al. (2017), who found that hyperuricemia correlated with HE severity in cirrhotic patients. ^[14]

Our study found a significant correlation between serum uric acid and key LFT parameters: Total Bilirubin (r = +0.43, p < 0.001): Suggesting that elevated uric acid is associated with cholestasis and worsening hepatic dysfunction. Serum Albumin (r = -0.39, p < 0.001): The inverse relationship suggests that hypoalbuminemia in advanced liver disease contributes to hyperuricemia. AST (r = +0.34, p < 0.01) and ALT (r = +0.21, p = 0.04): Indicating that liver injury contributes to altered purine metabolism and uric acid accumulation. These correlations are consistent with the findings of Xu et al. (2019), who reported a strong association between hyperuricemia and liver function deterioration in cirrhosis. ^[15]

Given the strong correlation between serum uric acid levels and liver disease severity, uric acid may be considered a potential biomarker for monitoring disease progression in CLD patients. Elevated uric acid levels in HE patients also suggest a possible role in hepatic neuroinflammation, warranting further research on its pathophysiological significance. ^[16]

Our study highlights a significant correlation between serum uric acid and the severity of CLD, HE, and liver dysfunction. The findings align with previous studies, reinforcing the potential role of uric acid as a prognostic marker in liver disease. Future studies with larger sample sizes are needed to explore therapeutic implications and the causal mechanisms behind these associations.

Uric acid is an old molecule with many new applications and it has also been studied in various metabolic diseases, cardiovascular diseases and chronic kidney disease. In this study it has been found that uric acid has a significant correlation with BMI, waist circumference and hypercholesterolemia. Hyperuricemia is also associated with both alcoholic and nonalcoholic liver diseases due to increased oxidative stress and inflammatory actions. This study also concluded that hyperuricemia is associated with increased number of cases both with cirrhosis and fatty liver. This clearly indicates that hyperuricemia in fatty liver patients, who are nonalcoholic have considerable risk for future progression to cirrhosis of liver. Because of its association with BMI, waist circumference and hypercholesterolemia, hyperuricemia may be considered as one the risk factor for metabolic syndrome.

1. Benerji D. Comparative Study of ALT, AST, GGT and Uric Acid Levels in Liver Diseases. IOSR J Dent Med Sci. 2013;7:72-5.
2. Afzali A, Weiss NS, Boyko EJ, Ioannou GN. Association between serum uric acid level and chronic liver disease in the United States. Hepatol Baltim Md. 2010;52(2):578-89.
3. Paul R, Chakravarti H, Mandal SK, Chatterjee S, Choudhury P. Study of serum uric acid in chronic liver disease and its relation with other parameters. Int Res J Pharm. 2013;4(7):162-7.
4. Ruhl CE, Everhart JE. Coffee and caffeine consumption reduce the Risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2005; 128:24-32.
5. Afzali A,   Weiss   NS,   Boyko   EJ,   Ioannou   Association between serum uric acid level and chronic liver disease in the United States. Hepatol Baltim Md. 2010;52(2):578-89.9.
6. Wang Q. Serum uric acid levels and their association with liver  function  and  disease  severity  in  chronic liver    disease        Journal    of    Hepatology.2016;64(5):1031-8.
7. Frelikh The role  of  serum  uric  acid  in  predicting outcomes   of   hepatic   encephalopathy   in   cirrhotic patients. Liver International.2019;39(2):271–9.11.
8. Friedman LS.Liver function tests and the diagnosis of liver disease. Clinical Cornerstone.2003;5(3):1-12.
9. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and Gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 2009; 136:477-485.
10. Ioannou GN, Weiss NS, Kowdley KV, Dominitz JA. Is obesity a risk Factor for cirrhosis-related death or hospitalization? A population-based Cohort study. Gastroenterology 2003; 125:1053-1059
11. García-Tsao G,  Lim  Management  and  treatment of  patients  with  cirrhosis  and  portal  hypertension". Hepatology.2009:49(2):471-85.
12. Benerji D. Comparative Study of ALT, AST, GGT & Uric Acid Levels in Liver Diseases. IOSR J Dent Med Sci. 2013;7:72-5.
13. Wright G,    Jalan        Management    of    hepatic encephalopathy   in   patients   with   cirrhosis.   Best Practice   &   Research   Clinical   Gastroenterology. 2007;21(1):95-110.
14. Jiang Serum  uric  acid  as  a  biomarker  for  hepatic and  renal  function  in  chronic  liver  disease  patients. European Journal of Gastroenterology & Hepatology, 2015;27(7):782-9.
15. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008;359:1811-1821.
16. Edwards NL. The role of hyperuricemia in vascular disorders. Curr Opin Rheumatol 2009;21:132-137.