Liver diseases, which include both acute and chronic conditions, represent a significant global health burden, contributing to morbidity and mortality across diverse populations. Acute liver disease is often characterized by the sudden onset of liver dysfunction, which may be reversible with timely and effective interventions.1 In contrast, chronic liver disease develops gradually over time, and if untreated, it can progress to more severe conditions like cirrhosis or even hepatocellular carcinoma (HCC). This cross-sectional study aims to explore the clinico-hematological issues in both acute and chronic liver disease, as well as their clinical correlations, shedding light on how these factors can influence diagnosis, treatment, and prognosis.2

The liver plays a pivotal role in various metabolic processes, including detoxification, protein synthesis, and nutrient storage. Therefore, any disturbance in liver function can have profound systemic effects. Acute liver failure (ALF) is a rapidly progressing condition, often precipitated by viral infections, toxic substances such as alcohol or drugs, and ischemia.3 On the other hand, chronic liver diseases (CLDs), which include conditions like chronic viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease (NAFLD), are more insidious in nature and often evolve into cirrhosis and end-stage liver disease over time. Early detection and intervention are critical in both acute and chronic liver conditions to prevent irreversible damage to the liver.4

Haematological abnormalities are commonly seen in both acute and chronic liver diseases and can serve as important diagnostic and prognostic indicators. In acute liver diseases, elevated levels of liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are often used as biomarkers of hepatocellular injury.5 In chronic liver conditions, more complex hematological changes may occur, such as thrombocytopenia and anemia due to hypersplenism caused by portal hypertension, or coagulopathy resulting from impaired synthesis of clotting factors by the liver. These hematological manifestations play a key role in assessing the severity of liver disease, determining the need for interventions, and predicting patient outcomes.6

Moreover, the clinical presentation of liver disease, such as jaundice, ascites, or hepatic encephalopathy, often correlates with specific hematological findings. For instance, a patient with jaundice and elevated liver enzymes might have acute liver injury, while a patient presenting with ascites and thrombocytopenia might indicate cirrhosis. Early recognition of these correlations allows healthcare professionals to categorize the disease stage, inform treatment decisions, and improve patient management.7

Recent advancements in diagnostic technologies have enhanced our understanding of liver diseases. One such advancement is the identification of biomarkers, such as microRNA-122, which have been found to correlate with hepatocellular damage and liver injury. These biomarkers provide a non-invasive method for diagnosing liver diseases and monitoring their progression. Additionally, the role of the gut-liver axis in liver disease has gained significant attention, as studies have shown that alterations in gut microbiota can contribute to inflammation, fibrosis, and other liver dysfunctions. This growing body of research opens new doors for potential therapeutic strategies targeting the microbiome as part of a comprehensive treatment plan for liver diseases.8

The clinico-hematological aspects of acute and chronic liver diseases are integral to the diagnosis, prognosis, and management of these conditions. The ability to correlate clinical findings with hematological parameters is vital for early disease detection and intervention, especially in liver diseases that progress silently. Ongoing research continues to deepen our understanding of the underlying pathophysiology of liver diseases, offering hope for more effective treatments and better patient outcomes. As our knowledge expands, it is essential to integrate the latest scientific advances into clinical practice to enhance patient care and improve the management of liver diseases worldwide.

The present study was a cross-sectional observational study conducted at the Postgraduate Department of Medicine, FH Medical College, Agra. It aimed to investigate the clinico-hematological issues in patients with acute and chronic liver diseases and explore their clinical correlations. The study population consisted of all patients diagnosed with liver diseases who attended the Medicine Department of FH Medical College, Agra. The study was carried out over a period of 18 months, during which a total of 138 patients were included. The sample size for the study was calculated using the formula:

N = Z² x p (1-p) / d²,

Where:

N represents the required sample size, Z is the normal deviant for a 95% confidence interval (Z = 1.96),

p is the estimated prevalence value (9%), d is the margin of error (5%).

The final sample size calculated was 138 patients.

   Inclusion criteria for the study were:

Male patients aged between 18 and 75 years.

Patients diagnosed with alcoholic liver cirrhosis with signs of chronic liver cell failure, confirmed through clinical examination and substantiated by histopathological evidence and imaging.

Patients with non-alcoholic liver diseases, end-stage liver diseases, chronic liver diseases (CLD), and hepatitis, confirmed through clinical evaluation and imaging.

Patients who provided written informed consent to participate in the study.

Exclusion criteria:

Patients aged over 75 years.

Patients with liver toxicity caused by anti-tubercular drugs (ATT).

Patients unwilling to participate in the study.

The study was observational and hospital-based. After obtaining written informed consent from all participants, detailed data was collected, including patient names, ages, sex, and medical history. Each patient underwent a thorough clinical examination, during which personal, family, and drug history were documented along with demographic information.

Laboratory investigations, including complete blood counts (CBC), liver function tests (LFT), prothrombin time (PT), international normalized ratio (INR), and abdominal ultrasound (USG W/A), were performed on all patients. Hematological parameters measured included hemoglobin (Hb), total leukocyte count (TLC), differential leukocyte count (DLC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), reticulocyte count, platelet count, mean platelet volume (MPV), and red cell distribution width (RDW).

The study focused on identifying hematological issues in liver disease patients, such as anemia, leucocytosis, leukopenia, and thrombocytopenia. Anemia was categorized based on grading, and patients were classified according to their Model for End-Stage Liver Disease (MELD) score and Child-Turcotte-Pugh (CTP) class. The associations between MELD scores, CTP scores, and hemoglobin (Hb) levels were analyzed using one-way analysis of variance (ANOVA), with post hoc analysis performed using the Bonferroni test. A p-value of less than 0.05 was considered statistically significant.

Data collection, processing, and analysis were carried out meticulously to ensure that all relevant hematological and clinical correlations were studied accurately, enabling a comprehensive understanding of clinico-hematological issues in patients with acute and chronic liver diseases. The findings aim to contribute to improving the diagnosis, management, and overall care of patients with liver diseases at our medical institution.

Table-1: Distribution according to age

In the study, the clinical parameters of the groups were evaluated, revealing a mean weight of 67.28 kg (SD ± 7.28). The body mass index (BMI) averaged 26.67 kg/m² (SD ± 4.38).

Table-2: Distribution according to Severity of anaemia

Table-3: Distribution of Cases According to the MCV Values and haemoglobin level.

Table-4: Distribution according to INR count and RBC type

The distribution of cases according to (INR) indicated that 20 individuals (14.49%) had an INR of 1. In contrast, a significant majority, 118 cases (85.51%), had an INR greater than 1. The overall mean INR was 1.67 (SD ± 0.52). This distribution highlighted a high prevalence of coagulopathy within the study population, suggesting impaired liver function and increased bleeding risk associated with their conditions.

The distribution of cases according to red blood cell (RBC) type revealed that 74 individuals (53.62%) had normocytic RBCs. Microcytic RBCs were observed in 38 cases (27.54%), while macrocytic RBCs were present in 24 cases (17.39%). Additionally, 2 cases (1.45%) exhibited dimorphic RBCs. This distribution, totaling 138 cases, highlighted the predominant presence of normocytic cells, along with notable occurrences of microcytic and macrocytic types, reflecting the diverse hematological changes associated with liver disease.

Table-5: Distribution according to MELD score

In the analysis of the Model for End-Stage Liver Disease (MELD) score, it was found that 49 individuals (35.51%) had a score of less than 12, while a larger group of 89 cases (64.49%) had scores greater than 12. This distribution highlighted a significant prevalence of advanced liver disease within the study population.

Table-6: Patients in MELD Group and Its Correlation with Severity of Anaemia

The correlation between MELD score groups and the severity of anemia revealed distinct differences in hemoglobin levels among patients. In the MELD <12 group, 16 individuals (32.65%) had normal hemoglobin levels, while 12 (24.49%) had mild anemia. Moderate anemia was present in 13 cases (26.53%), and severe anemia affected 8 individuals (16.33%). Conversely, in the MELD >12 group, only 3 patients (3.37%) had normal hemoglobin levels, with 4 (4.49%) experiencing mild anemia. The prevalence of moderate anemia was higher in this group, with 32 cases (35.96%), while severe anemia was significantly more common, affecting 50 patients (56.18%). This analysis showed the strong association between higher MELD scores and increased severity of anemia, emphasizing the clinical implications of liver dysfunction.

Liver diseases, both acute and chronic, frequently lead to hematological complications such as anemia, thrombocytopenia, and leucopenia, which can significantly affect patient outcomes. Anemia in liver disease often arises from multiple factors, including gastrointestinal bleeding, portal hypertension, chronic inflammation, and impaired liver function. The present study aimed to investigate the distribution of red blood cell (RBC) types and the correlation between the Model for End-Stage Liver Disease (MELD) score and anemia severity in liver disease patients, highlighting the complex interplay between hematological abnormalities and liver dysfunction.

The age distribution in our study indicated that the majority of patients were middle-aged, with the highest proportion of cases observed in the 51-60 years age group (29.71%). This is consistent with previous studies, such as Joshi D et al. (2023)9 and Tomar MSI et al. (2023)10, who reported a similar age distribution, with a predominance of middle-aged individuals affected by liver disease. This demographic trend underscores the increasing prevalence of liver disease in adults, particularly in

those aged 40-60 years, who are at greater risk of developing chronic liver conditions such as cirrhosis and NAFLD.

In terms of hematological abnormalities, our study showed that the majority of participants had severe anemia (43.48%), followed by moderate anemia (32.61%). This finding is consistent with the work of Scheiner B et al. (2020)11, who reported that mild anemia was most prevalent in their study population; however, our study found a higher prevalence of severe anemia. This could be due to the advanced stage of liver disease in the majority of our patients, who were often in later stages of cirrhosis, as indicated by their MELD scores.

Regarding RBC morphology, the study found that most patients had normocytic anemia (56.52%), followed by microcytic anemia (30.43%) and macrocytic anemia (13.04%). This is in line with previous studies by Kaur J et al. (2021)12, who also found that normocytic anemia was the most prevalent in liver disease patients. The presence of microcytic anemia in a significant proportion of patients suggests that some patients may have concurrent iron deficiency, commonly seen in chronic diseases or gastrointestinal bleeding. Macrocytic anemia, although less common, is often associated with vitamin B12 or folate deficiencies, which can occur in liver disease due to malabsorption or poor nutritional status.

The MELD score is an important prognostic tool in liver disease, particularly in cirrhotic patients, as it helps predict the risk of mortality and need for liver transplantation. In our study, patients with a MELD score greater than 12 showed a significantly higher prevalence of moderate to severe anemia compared to those with lower MELD scores. This finding aligns with Scheiner B et al. (2020), who also observed a correlation between higher MELD scores and the severity of anemia. The MELD score, which incorporates bilirubin, creatinine, and INR levels, reflects liver function and helps identify patients at high risk for complications, including anemia.

Additionally, the platelet count distribution in our study revealed that the majority of patients had thrombocytopenia (57.97%), a common finding in liver disease due to hypersplenism caused by portal hypertension. Joshi D et al. (2023)9 and Tomar MSI et al. (2023) 10similarly reported a high prevalence of thrombocytopenia in patients with chronic liver disease, reinforcing the association between liver dysfunction and impaired platelet production. Thrombocytopenia can lead to bleeding complications, further complicating the management of patients with advanced liver disease.

The International Normalized Ratio (INR) is another crucial parameter in liver disease, reflecting the liver's ability to synthesize clotting factors. In our study, 85.51% of patients had an elevated INR, indicating impaired coagulation, which is a hallmark of liver dysfunction. These findings are consistent with those of Scheiner B et al. (2020), who also observed elevated INR values in liver disease patients, highlighting the increased risk of bleeding and coagulopathy associated with severe liver dysfunction.

The distribution of leukocyte counts (TLC) in our study showed a higher proportion of patients with leukocytosis (45.65%), suggesting underlying infection or inflammation. Leukopenia, observed in 39.13% of cases, may reflect bone marrow suppression, a common issue in advanced liver disease. These findings contrast with those of Joshi D et al. (2023), who did not find a significant correlation between TLC and anemia severity. The elevated TLC in our study may be indicative of the systemic inflammatory response often seen in liver disease, particularly in those with active infections or exacerbations of chronic liver disease.13,14

In conclusion, this study highlights the significant hematological abnormalities observed in patients with liver disease, particularly anemia, thrombocytopenia, and leukocytosis. These findings underscore the importance of comprehensive clinical and hematological assessment in liver disease management, as they help gauge disease severity and predict potential complications. The correlation between MELD scores, anemia severity, and other hematological parameters further emphasizes the need for early detection and intervention in patients with advanced liver dysfunction. Future research should continue to explore the pathophysiological mechanisms underlying these hematological abnormalities and their impact on patient outcomes in liver disease.

The present study underscores notable associations between liver dysfunction, red blood cell (RBC) morphology, and the severity of anaemia. A predominant number of cases exhibited normocytic RBCs, suggesting anaemia of chronic disease or liver-related hematological changes. A significant portion also presented with microcytic RBCs, which are indicative of iron deficiency anaemia, and macrocytic RBCs, potentially pointing to deficiencies in vitamin B12 or folate. These findings highlight the complex and diverse hematological manifestations observed in patients with liver disease.

Additionally, the distribution of cases based on the MELD score reveals a substantial prevalence of advanced liver dysfunction, with 64.49% of patients having a MELD score above 12, signaling severe liver disease and an elevated risk of complications. This finding aligns with the observed correlation between MELD scores and anaemia severity, where higher MELD scores were linked to an increased likelihood of moderate to severe anaemia. Specifically, patients with MELD scores greater than 12 exhibited significantly higher rates of severe anaemia, with only a small percentage maintaining normal haemoglobin levels.

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