Liver diseases are a major cause of global morbidity and mortality and represent a significant public health burden worldwide. [1] The liver performs essential functions, including metabolism, detoxification, synthesis of proteins and clotting factors, bile excretion, and regulation of hematological homeostasis. Consequently, hepatic dysfunction can result in a wide spectrum of systemic and hematological abnormalities. [1] Chronic liver disease (CLD) is characterized by progressive deterioration of liver functions persisting for more than six months, including impairment in the synthesis of clotting factors and other proteins, detoxification of harmful metabolic products, and excretion of bile [2]. It is a continuous process of hepatic inflammation, destruction, and regeneration of liver parenchyma, ultimately leading to fibrosis and cirrhosis [3]. Acute liver disease, in contrast, develops rapidly over days to weeks and may result from viral infections, alcohol-induced injury, toxins, metabolic disorders, or drug-induced hepatotoxicity. Liver diseases represent a major healthcare challenge in India. Chronic liver diseases and cirrhosis account for nearly 2.1% of all deaths in India [4]. Delayed clinical presentation remains a major obstacle in management, with many patients presenting only after hepatic decompensation has occurred [5]. Cirrhosis is among the leading causes of disability-adjusted life years and years of life lost worldwide [6]. Major etiological factors include chronic alcohol consumption, viral hepatitis, obesity, diabetes mellitus, and drug-induced liver injury. Viral hepatitis continues to be highly prevalent, while alcohol-associated liver disease and non-alcoholic fatty liver disease are increasingly common worldwide [6]. The liver plays a crucial role in hematopoiesis, iron metabolism, thrombopoietin production, and synthesis of coagulation factors. Consequently, liver diseases are frequently associated with hematological abnormalities such as anemia, leukocyte abnormalities, thrombocytopenia, and coagulation disorders. Approximately 75% of patients with chronic liver disease are reported to have anemia [7]. The anemia is commonly normocytic-normochromic or mildly macrocytic, although microcytic anemia may occur secondary to chronic gastrointestinal blood loss. Thrombocytopenia is another common hematological abnormality and is observed in nearly 30–64% of cirrhotic patients [7,8]. Chronic liver disease leads to progressive distortion of liver architecture, resulting in fibrosis, cirrhosis, portal hypertension, and hypersplenism, all of which significantly affect the peripheral blood picture [9]. Hematological manifestations may result from hepatocellular failure, hypersplenism, nutritional deficiencies, alcoholism, gastrointestinal bleeding, reduced erythrocyte survival, and impaired synthesis of proteins required for hematopoiesis and coagulation [10]. Coagulation abnormalities are particularly common due to impaired synthesis of clotting factors and cholestatic dysfunction [11]. Despite the high prevalence of hematological abnormalities in liver diseases, comparative evaluation of hematological changes in acute and chronic liver diseases remains limited. Understanding these changes is important for early diagnosis, assessment of disease severity, prevention of complications, and improvement of patient outcomes. Therefore, the present study was undertaken to evaluate the various hematological changes occurring in patients with acute and chronic liver diseases and to assess their clinical significance.

Study Design and Setting This hospital-based observational study was conducted in the Department of Pathology at F.H. Medical College and Hospital, Agra, Uttar Pradesh, India, over a period of 24 months from 2024 to 2026. The study was undertaken to evaluate and compare the haematological changes associated with acute and chronic liver diseases. Study Population The study included 120 patients diagnosed with acute or chronic liver disease who presented to the Department of Pathology for haematological evaluation during the study period. Patients of both genders aged between 20 and 60 years were included in the study. Diagnosis of acute and chronic liver disease was established based on clinical presentation, biochemical investigations, liver function tests, radiological findings, and relevant serological investigations wherever indicated. Inclusion and Exclusion Criteria Inclusion Criteria • Patients diagnosed with acute or chronic liver disease. • Patients of both genders aged between 20 and 60 years. • Patients willing to provide informed consent for participation in the study. Exclusion Criteria • Patients with primary coagulation disorders. • Patients with pre-existing haematological disorders. • Patients with severe cardiac, renal, or neurological diseases. • Patients unwilling to participate in the study. • Patients who did not provide informed consent. Ethical Considerations The study protocol was reviewed and approved by the Institutional Ethics Committee of F.H. Medical College and Hospital, Agra. All procedures performed during the study were conducted in accordance with institutional ethical standards. Written informed consent was obtained from all participants prior to enrolment in the study. Methodology A detailed clinical history was obtained from all enrolled patients, followed by thorough general and systemic examination. Relevant demographic details, clinical findings, duration of illness, associated comorbidities, and possible etiological factors were recorded using a predesigned proforma. Venous blood samples were collected under aseptic precautions for haematological investigations. Complete haemogram analysis was performed using an automated haematology analyser according to standard laboratory protocols. The evaluated parameters included haemoglobin concentration, red blood cell (RBC) count, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC). Peripheral blood smear examination was performed to assess red blood cell morphology and overall blood picture. Reticulocyte count assessment was carried out wherever indicated. White blood cell abnormalities were evaluated using total leukocyte count and differentialleukocyte count. Platelet count was assessed in all patients to evaluate thrombocytopenia and associated platelet abnormalities. Coagulation parameters including prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured to assess haemostatic abnormalities associated with liver dysfunction. Additional investigations including liver function tests, viral marker studies, ultrasonography findings, and upper gastrointestinal endoscopy findings were reviewed wherever available and clinically indicated. The haematological parameters observed in patients with acute liver disease were compared with those observed in chronic liver disease in order to evaluate the pattern, frequency, and severity of haematological abnormalities. Statistical Analysis Data collected during the study were entered into Microsoft Excel 2017 and analysed using the Statistical Package for the Social Sciences (SPSS) software version 28. Quantitative variables were expressed as mean ± standard deviation, whereas qualitative variables were presented as frequencies and percentages. Comparisons between study groups were performed using the independent Student’s t-test for continuous variables and Chi-square test for categorical variables, wherever appropriate. Statistical significance was considered at a p-value of less than 0.05

Table 1. Demographic Characteristics of Study Participants Variable Category No. of Cases Percentage Age Group 20–30 19 15.83% 31–40 40 33.33% 41–50 37 30.83% 51–60 24 20.00% Gender Male 65 54.17% Female 55 45.83% Occupation Shopkeepers 21 17.50% Retired personnel 17 14.17% Farmers 19 15.83% Government employed 31 25.83% Unemployed 12 10.00% Others 20 16.67% Mean age: 50.23 ± 12.30 years Graph-1: Age Group distribution Graph-2:Gender distribution. Graph-3: Occupations. The present study included participants belonging to different age groups, genders, and occupational backgrounds. The majority of participants were in the 31–40 years age group, accounting for 33.33% of cases, followed by the 41–50 years age group comprising 30.83% of cases. Participants aged 51–60 years constituted 20.00%, while the lowest proportion (15.83%) belonged to the 20–30 years age group. The mean age of the study population was 50.23 ± 12.30 years. Gender distribution showed a slight male predominance, with 65 males (54.17%) and 55 females (45.83%). Occupational analysis revealed that government employees formed the largest group (25.83%), followed by shopkeepers (17.50%), farmers (15.83%), retired personnel (14.17%), and unemployed individuals (10.00%). Participants involved in other occupations accounted for 16.67% of the study population. Table 2. Clinical Parameters. Clinical Parameter Mean ± SD BMI (kg/m²) 23.89 ± 5.75 Weight (kg) 67.89 ± 13.10 Assessment of clinical parameters demonstrated that the mean Body Mass Index (BMI) of the study participants was 23.89 ± 5.75 kg/m², indicating that most individuals had BMI values within or near the normal range. The mean body weight of the participants was 67.89 ± 13.10 kg. These findings provide baseline anthropometric characteristics of patients with acute and chronic liver diseases included in the study. Table 3. Overall Haematological Abnormalities Haematological Abnormality No. of Cases Percentage Anaemia 103 85.83% Leukopenia 9 7.50% Neutrophilic Leukocytosis 3 2.50% Thrombocytopenia 60 50.00% Graph 4: Distribution according to Haematological profile. The study revealed a high prevalence of haematological abnormalities among patients with liver diseases. Anaemia was the most common abnormality, observed in 103 cases (85.83%), indicating that reduced haemoglobin levels are a major haematological manifestation in liver disease patients. Thrombocytopenia was present in 60 cases (50.00%), suggesting significant platelet abnormalities associated with hepatic dysfunction and possible hypersplenism. Leukopenia was identified in 9 cases (7.50%), while neutrophilic leukocytosis was seen in 3 cases (2.50%). These findings demonstrate that haematological derangements involving red blood cells, white blood cells, and platelets are common in acute and chronic liver diseases. Table 4. Severity and Type of Anaemia Parameter Category No. of Cases Percentage Severity of Anaemia Normal 16 15.53% Mild 13 12.62% Moderate 56 54.37% Severe 18 17.48% RBC Size Pattern Normocytic 35 29.17% Macrocytic 45 37.50% Microcytic 18 15.00% Dimorphic 3 2.50% Graph 5 : Distribution according to the severity of anaemia Graph 6: Distribution According to Haematological Parameter of RBC Size. Evaluation of anaemia severity showed that moderate anaemia was the most frequent pattern, observed in 56 cases (54.37%). Severe anaemia was present in 18 cases (17.48%), while mild anaemia was noted in 13 cases (12.62%). Normal haemoglobin levels were found in 16 cases (15.53%). Analysis of red blood cell size patterns demonstrated that macrocytic anaemia was the most common morphological type, accounting for 37.50% of cases, followed by normocytic anaemia in 29.17% and microcytic anaemia in 15.00% of cases. Dimorphic anaemia was the least common pattern, observed in 2.50% of cases. These findings indicate that macrocytosis and moderate anaemia are predominant haematological abnormalities among patients with liver diseases. Table 5. Peripheral Smear Morphological Abnormalities Peripheral Smear Finding No. of Cases Percentage Target Cells 2 1.67% Spherocytes 1 0.83% Spur Cells (Acanthocytes) 1 0.83% Schistocytes 1 0.83% Graph 7:Distribution According to Haematological Parameters: RBC Shape (Peripheral Smear Findings) Peripheral smear examination revealed relatively few abnormal red blood cell morphological changes among the study participants. Target cells were the most commonly observed abnormality, seen in 2 cases (1.67%). Spherocytes, spur cells (acanthocytes), and schistocytes were each identified in 1 case (0.83%). The low frequency of abnormal RBC morphologies suggests that although morphological changes may occur in liver disease, they were comparatively uncommon in the present study population. Table 6. White Blood Cell Abnormalities. WBC Finding No. of Cases Percentage Neutrophilic Leukocytosis 3 2.50% Leukopenia 1 0.83% Normal WBC Count 116 96.67% Graph 8:Distribution According to Haematological Parameters White Blood Cell (WBC) Abnormalities. Assessment of white blood cell abnormalities showed that the majority of participants had normal WBC counts, accounting for 116 cases (96.67%). Neutrophilic leukocytosis was identified in 3 cases (2.50%), indicating inflammatory or infectious processes in a small subset of patients. Leukopenia was observed in 1 case (0.83%). Overall, significant white blood cell abnormalities were relatively uncommon in the study population compared to anaemia and platelet abnormalities.

The present study evaluated haematological alterations in patients with acute and chronic liver diseases and demonstrated that anaemia was the most frequent abnormality, followed by thrombocytopenia, while leukocyte abnormalities were relatively uncommon. Macrocytic anaemia with moderate severity predominated, and most patients exhibited normal white blood cell counts. [11] These findings reinforce the strong association between hepatic dysfunction and multisystem haematological derangements, reflecting disease severity, chronicity, and underlying pathophysiological disturbances. The demographic profile revealed a predominance of patients in the 31–50 years age group with a mean age of 50.23 ± 12.30 years, indicating that liver diseases commonly affect middle-aged individuals. This may be attributed to cumulative exposure to risk factors such as alcohol consumption, viral hepatitis, metabolic syndrome, and lifestyle-related influences. A slight male predominance observed in the present study is in agreement with observations reported by Joshi D et al. (2023) [11] and Khan F et al. (2018) [12], which may be explained by higher alcohol intake, occupational exposure, and behavioural risk patterns among males. Anaemia was the most common haematological abnormality (85.83%), findings that closely parallel those of Fatima Q (2018) [7] and Gonzalez-Casas R et al. (2009) [13], who also reported a high burden of anaemia in liver disease populations. The development of anaemia is multifactorial, involving chronic gastrointestinal blood loss due to portal hypertensive gastropathy and varices, hypersplenism with sequestration and destruction of blood cells, bone marrow suppression, and nutritional deficiencies including iron, folate, and vitamin B12 deficiency. Additionally, chronic inflammatory states and impaired hepatic protein synthesis contribute to anaemia of chronic disease, particularly in advanced liver dysfunction. Macrocytic anaemia emerged as the predominant morphological pattern in the present study. This observation is consistent with findings of Kaur J et al. (2021) [14] and Joshi D et al. (2023) [11], where macrocytosis was frequently associated with alcohol-related and advanced hepatic disease. The mechanism is attributed to alcohol-induced marrow toxicity, folate deficiency, and altered erythrocyte membrane lipid composition, leading to increased mean corpuscular volume. Variations in prevalence across studies may be influenced by differences in etiological profiles and nutritional status of study populations. Thrombocytopenia was observed in 50% of patients, findings comparable with those of Bialek SR (2008) and Kaur J et al. (2021) [14], who reported similar ranges in cirrhotic cohorts. The underlying mechanisms include hypersplenism secondary to portal hypertension, reduced thrombopoietin production by the diseased liver, and direct bone marrow suppression. Clinically, thrombocytopenia represents an important marker of disease progression and portal hypertension severity. White blood cell abnormalities were relatively infrequent, with most patients showing normal leukocyte counts, consistent with findings of Dassani M et al. (2026) [15]. Leukopenia may result from hypersplenism, whereas leukocytosis is typically associated with intercurrent infections such as spontaneous bacterial peritonitis or urinary tract infections, as also noted by Khan F et al. (2018) [12]. Peripheral smear examination revealed occasional abnormalities including target cells, spur cells, spherocytes, and schistocytes. Target cells reflect altered lipid–cholesterol ratios in chronic liver disease, whereas spur cells are indicative of advanced hepatic dysfunction and are associated with poorer prognosis, as described by Acharya S et al. (2017) [16]. The relatively low frequency of these abnormalities in the present study may suggest a higher proportion of early to moderately advanced disease stages. Overall, the study highlights that simple and cost-effective investigations such as complete blood count and peripheral smear examination remain valuable tools for early detection, severity assessment, and monitoring of liver disease progression. However, limitations such as single-centre design, moderate sample size, and lack of histopathological correlation should be considered when interpreting the findings. Limitations and Future Directions This study is limited by its single-centre design, relatively small sample size, and absence of histopathological correlation and longitudinal follow-up, which may restrict generalisability and prognostic validation. Future multicentric studies with larger, well-stratified cohorts based on aetiology and disease severity are warranted to confirm these findings and to better define the diagnostic and prognostic utility of haematological parameters in acute and chronic liver diseases.

The present study highlights a broad spectrum of haematological abnormalities associated with acute and chronic liver diseases. Anaemia emerged as the most prevalent abnormality, predominantly of moderate severity, with macrocytic indices being the most frequent morphological pattern. Thrombocytopenia was also commonly observed, reflecting the combined effects of hypersplenism, reduced thrombopoietin synthesis, and impaired hepatic function on platelet production and survival. In contrast, white blood cell abnormalities were relatively uncommon, with the majority of patients demonstrating normal leukocyte counts. Peripheral smear examination revealed occasional red cell morphological changes, including target cells, spherocytes, spur cells, and schistocytes, though these were infrequent findings overall. The study further demonstrated a slight male predominance and a higher occurrence of disease among middle-aged individuals. Overall, the findings indicate that haematological abnormalities are common in liver diseases and may serve as important markers of disease severity and prognosis. Early recognition and systematic evaluation of these parameters are essential for timely clinical management, prevention of complications, and improved patient outcomes in both acute and chronic liver disease.

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