Chronic liver disease (CLD) comprises a spectrum of progressive hepatic disorders characterised by persistent inflammation, fibrosis and gradual deterioration of liver function. Common causes include alcohol-associated liver disease, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, autoimmune hepatitis and cholestatic disorders. As CLD progresses from compensated disease to cirrhosis and decompensation, patients may develop portal hypertension, ascites, variceal bleeding, hepatic encephalopathy, jaundice and various haematological abnormalities. Among these, anemia is one of the most frequent and clinically important complications. Approximately two-thirds of patients with advanced CLD may have anemia, and its prevalence increases with worsening liver dysfunction [1,2]. The pathogenesis of anemia in CLD is complex and frequently multifactorial. Chronic or occult gastrointestinal blood loss from esophageal or gastric varices, portal hypertensive gastropathy, gastric antral vascular ectasia and peptic ulcer disease may result in iron-deficiency anemia. Nutritional deficiencies, particularly iron, folate and vitamin B12 deficiency, may arise from inadequate dietary intake, malabsorption or chronic alcohol consumption. Hypersplenism secondary to portal hypertension can cause sequestration and premature destruction of blood cells. Additional mechanisms include reduced erythropoietin response, chronic inflammation, impaired bone-marrow function, haemolysis, dilution caused by fluid retention and direct toxic effects of alcohol on erythropoiesis [2,3]. The morphological pattern of anemia may provide clues regarding its underlying mechanism. Microcytic hypochromic anemia generally suggests iron deficiency due to chronic blood loss, while macrocytosis may occur because of alcohol use, folate or vitamin B12 deficiency and alterations in the red-cell membrane associated with liver dysfunction. Normocytic normochromic anemia may be associated with chronic inflammation, haemolysis, renal dysfunction or bone-marrow suppression. Therefore, evaluation of complete blood count, red-cell indices, peripheral smear, reticulocyte count and iron profile is essential for characterising anemia in patients with CLD. Anemia can aggravate fatigue, dyspnoea, reduced exercise tolerance, tissue hypoxia and cardiovascular stress. It is also associated with hepatic decompensation, increased hospitalisation and higher liver-related mortality [1,4]. Nevertheless, anemia may be overlooked because its manifestations overlap with those of underlying liver disease. The World Health Organization defines anemia in adults as haemoglobin below 13.0 g/dL in men and below 12.0 g/dL in non-pregnant women [5]. Determining its prevalence, severity, morphological pattern and relationship with the cause and severity of CLD may facilitate early investigation and targeted management. Therefore, the present study evaluated the prevalence and clinical profile of anemia among patients with chronic liver disease. AIM To determine the prevalence and clinical profile of anemia among patients with chronic liver disease. OBJECTIVES 1. To estimate the prevalence, severity and morphological patterns of anemia among patients with chronic liver disease. 2. To assess the association of anemia with the aetiology, clinical manifestations, laboratory parameters and severity of chronic liver disease.

Source of Data Data were obtained from patients with chronic liver disease who attended the outpatient department or were admitted to the Department of General Medicine and associated gastroenterology services of the study hospital during the study period. Information was collected through patient interviews, clinical examinations, inpatient and outpatient records, and laboratory and radiological reports. Study Design The study was a hospital-based cross-sectional observational study. Study Location The study was conducted in the Department of General Medicine at a tertiary-care teaching hospital. Patients were recruited from the General Medicine outpatient department, emergency department, medical wards and intensive care unit. Study Duration The study was conducted over a period of 18 months, including patient recruitment, data collection, laboratory evaluation, data verification and statistical analysis. Study Population The study population consisted of adult patients diagnosed with chronic liver disease on the basis of clinical history, physical examination, biochemical investigations, ultrasonography, elastography, endoscopy, computed tomography, magnetic resonance imaging or histopathology, wherever applicable. Sample Size A total of 200 eligible patients with chronic liver disease were included in the study. All patients who met the eligibility criteria during the study period were recruited until the required sample size was achieved. The prevalence of anemia was calculated as: Inclusion Criteria 1. Patients aged 18 years or older. 2. Patients of either sex. 3. Patients diagnosed with chronic liver disease of at least six months’ duration. 4. Patients with compensated or decompensated chronic liver disease. 5. Patients who provided written informed consent. 6. Patients for whom complete clinical and haematological evaluation was available. Exclusion Criteria 1. Patients with acute liver failure without evidence of pre-existing CLD. 2. Pregnant or lactating women. 3. Patients with known haematological malignancy, aplastic anemia, myelodysplastic syndrome or inherited haemoglobinopathy. 4. Patients with active non-hepatic malignancy. 5. Patients with chronic kidney disease requiring dialysis. 6. Patients who had received a blood transfusion during the preceding four weeks. 7. Patients receiving erythropoietin or undergoing active chemotherapy. 8. Patients with major surgery, trauma or acute non-variceal haemorrhage immediately before enrolment. 9. Patients unwilling to provide consent. 10. Patients whose clinical or laboratory records were substantially incomplete. Operational Definitions Chronic liver disease was defined as clinical, biochemical, radiological or histological evidence of persistent liver disease for at least six months. Anemia was diagnosed according to WHO criteria as haemoglobin: • Below 13.0 g/dL in adult men. • Below 12.0 g/dL in non-pregnant adult women. Anemia was further classified according to haemoglobin concentration as: Severity Men Non-pregnant women Mild 11.0-12.9 g/dL 11.0-11.9 g/dL Moderate 8.0-10.9 g/dL 8.0-10.9 g/dL Severe <8.0 g/dL <8.0 g/dL Morphological classification was primarily based on mean corpuscular volume: • Microcytic anemia: MCV below 80 fL. • Normocytic anemia: MCV 80-100 fL. • Macrocytic anemia: MCV above 100 fL. • Dimorphic anemia: two distinct red-cell populations on peripheral smear or a mixed deficiency pattern. Procedure and Methodology After approval from the Institutional Ethics Committee, eligible patients were approached and the purpose of the study was explained in their preferred language. Written informed consent was obtained before enrolment. Each patient was assigned a unique study identification number. A detailed history was recorded regarding age, sex, residence, dietary habits, duration of liver disease, alcohol consumption, previous jaundice, viral hepatitis, gastrointestinal bleeding, blood transfusion, drug exposure and existing comorbidities. Symptoms suggestive of anemia fatigue, weakness, exertional dyspnoea, palpitations and dizziness were documented. Symptoms of hepatic decompensation, including abdominal distension, hematemesis, melena, altered sensorium, reduced urine output and pedal oedema, were also recorded. General and systemic examinations were performed. Pallor, icterus, pedal oedema, body mass index, pulse, blood pressure and respiratory rate were documented. Abdominal examination assessed hepatomegaly, splenomegaly, ascites and dilated abdominal veins. Signs of CLD, such as spider angiomas, palmar erythema, gynecomastia, testicular atrophy and asterixis, were recorded. Haematological evaluation included haemoglobin, total leukocyte count, platelet count, haematocrit, red-blood-cell count, MCV, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red-cell distribution width, reticulocyte count and peripheral-blood-smear examination. Iron studies, serum vitamin B12, serum folate, lactate dehydrogenase, bilirubin fractions and direct antiglobulin testing were performed when clinically indicated. Liver evaluation included serum bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, serum albumin, prothrombin time and international normalised ratio. Serum creatinine, blood urea, electrolytes, blood glucose and viral markers were assessed. Ultrasonography was used to evaluate liver morphology, portal-vein diameter, splenomegaly and ascites. Upper gastrointestinal endoscopy findings, including varices and portal hypertensive gastropathy, were recorded whenever available. The probable aetiology of CLD was classified as alcohol-associated, viral, metabolic, autoimmune, cholestatic, cryptogenic or other causes. Disease severity was evaluated using the Child-Pugh classification and Model for End-Stage Liver Disease score wherever the required variables were available. Sample Processing Approximately 8-10 mL of venous blood was collected from each participant using aseptic precautions: 1. Two millilitres were collected in an EDTA tube for complete blood count, red-cell indices, reticulocyte count and peripheral smear. 2. Approximately 2.7 mL were collected in a sodium-citrate tube for prothrombin time and INR. 3. The remaining blood was collected in a plain or serum-separator tube for liver-function tests, renal-function tests, iron studies, vitamin assays and other biochemical investigations. The complete blood count was performed using a calibrated automated haematology analyser. Peripheral smears were prepared, stained with Leishman stain and examined microscopically. Blood samples for biochemical testing were allowed to clot and were centrifuged to separate serum. Serum investigations were conducted using a calibrated automated biochemical analyser. Internal quality-control procedures were followed, and abnormal or doubtful results were rechecked. Data Collection Data were collected using a predesigned and pretested case-record form. The form included: • Sociodemographic information. • Aetiology and duration of CLD. • Symptoms and clinical signs. • Comorbidities and medication history. • Haematological and biochemical parameters. • Morphological type and severity of anemia. • Ultrasonography and endoscopy findings. • Child-Pugh class and MELD score. • History of hepatic decompensation and gastrointestinal bleeding. Completed forms were checked daily for accuracy and completeness. Data were anonymised before entry into the electronic database. A proportion of records was cross-checked against source documents to minimise transcription errors. Statistical Methods Data were entered into Microsoft Excel and analysed using SPSS, R or an equivalent statistical software package. Categorical variables were presented as frequencies and percentages. Continuous variables were assessed for normality using graphical methods and the Shapiro-Wilk test. Normally distributed data were expressed as mean and standard deviation, while skewed data were reported as median and interquartile range. The prevalence of anemia was presented as a percentage with a 95% confidence interval. The chi-square test or Fisher’s exact test was used to examine associations between categorical variables. Independent-samples t test was used to compare normally distributed continuous variables between two groups, while the Mann-Whitney U test was used for non-normally distributed variables. Analysis of variance or the Kruskal-Wallis test was applied for comparisons involving more than two groups. The association of anemia with age, sex, aetiology of CLD, gastrointestinal bleeding, splenomegaly, Child-Pugh class and other relevant variables was evaluated. Binary logistic regression analysis was performed to identify factors independently associated with anemia. Adjusted odds ratios with 95% confidence intervals were reported. Multicollinearity and model fit were assessed before interpreting the regression model. A two-tailed p value below 0.05 was considered statistically significant.

Table 1. Prevalence and clinical profile of anemia among patients with chronic liver disease (N=200) Study parameter Overall (N=200) Anemia present (n=137) Anemia absent (n=63) Effect estimate (95% CI) Test of significance P value Age, years, Mean (SD) 48.14 (12.04) 49.28 (11.74) 45.67 (12.38) MD: 3.61 (−0.02 to 7.24) Welch t=1.95 0.054 Male sex 126 (63.0%) 89 (65.0%) 37 (58.7%) OR: 1.30 (0.71-2.40) χ²=0.72 0.396 Female sex 74 (37.0%) 48 (35.0%) 26 (41.3%) Reference Duration of CLD, years, Mean (SD) 5.34 (3.10) 5.84 (3.17) 4.26 (2.71) MD: 1.58 (0.73-2.43) Welch t=3.63 <0.001* BMI, kg/m², Mean (SD) 22.58 (3.59) 22.18 (3.62) 23.46 (3.41) MD: −1.28 (−2.32 to −0.24) Welch t=−2.42 0.017* Current/past alcohol consumption 104 (52.0%) 77 (56.2%) 27 (42.9%) OR: 1.71 (0.94-3.13) χ²=3.08 0.079 Fatigue or easy fatigability 142 (71.0%) 111 (81.0%) 31 (49.2%) OR: 4.41 (2.29-8.47) χ²=21.22 <0.001* Pallor 137 (68.5%) 119 (86.9%) 18 (28.6%) OR: 16.53 (7.90-34.57) χ²=67.95 <0.001* Exertional dyspnoea 87 (43.5%) 72 (52.6%) 15 (23.8%) OR: 3.55 (1.82-6.94) χ²=14.36 <0.001* Pedal oedema 93 (46.5%) 76 (55.5%) 17 (27.0%) OR: 3.37 (1.78-6.39) χ²=14.09 <0.001* Ascites 107 (53.5%) 86 (62.8%) 21 (33.3%) OR: 3.37 (1.80-6.32) χ²=15.04 <0.001* Splenomegaly 89 (44.5%) 73 (53.3%) 16 (25.4%) OR: 3.35 (1.73-6.48) χ²=13.59 <0.001* Previous gastrointestinal bleeding 57 (28.5%) 49 (35.8%) 8 (12.7%) OR: 3.83 (1.69-8.69) χ²=11.27 0.001* Decompensated CLD 124 (62.0%) 98 (71.5%) 26 (41.3%) OR: 3.58 (1.92-6.67) χ²=16.78 <0.001* Compensated CLD 76 (38.0%) 39 (28.5%) 37 (58.7%) Reference Among 200 patients with chronic liver disease, 137 (68.5%) had anemia and 63 (31.5%) did not. The overall mean age was 48.14 ± 12.04 years. Patients with anemia were slightly older than those without anemia (49.28 ± 11.74 versus 45.67 ± 12.38 years); however, the difference was not statistically significant (MD=3.61 years, 95% CI: −0.02 to 7.24; p=0.054). Males constituted 63.0% of the study population, but sex was not significantly associated with anemia (OR=1.30, 95% CI: 0.71-2.40; p=0.396). The mean duration of CLD was significantly longer among anemic patients than among non-anemic patients (5.84 ± 3.17 versus 4.26 ± 2.71 years; MD=1.58, 95% CI: 0.73-2.43; p<0.001). Anemic patients also had a significantly lower mean BMI (22.18 ± 3.62 versus 23.46 ± 3.41 kg/m²; MD=−1.28, 95% CI: −2.32 to −0.24; p=0.017). Although alcohol consumption was more common among anemic patients, the association did not attain statistical significance (56.2% versus 42.9%; OR=1.71, 95% CI: 0.94-3.13; p=0.079). Clinical manifestations were substantially more frequent among patients with anemia. Fatigue was reported by 81.0% of anemic patients compared with 49.2% of non-anemic patients (OR=4.41, 95% CI: 2.29-8.47; p<0.001). Pallor had the strongest association with anemia and was observed in 86.9% of anemic patients compared with 28.6% of non-anemic patients (OR=16.53, 95% CI: 7.90-34.57; p<0.001). Exertional dyspnoea, pedal oedema, ascites and splenomegaly were also approximately three times more likely among anemic patients, with all associations being statistically significant. Previous gastrointestinal bleeding was present in 35.8% of anemic patients compared with 12.7% of non-anemic patients (OR=3.83, 95% CI: 1.69-8.69; p=0.001). Decompensated CLD was significantly more common among patients with anemia than among those without anemia (71.5% versus 41.3%; OR=3.58, 95% CI: 1.92-6.67; p<0.001). Table 2. Prevalence, severity and morphological patterns of anemia among patients with chronic liver disease Anemia parameter Frequency, n (%) 95% CI Test of significance P value Prevalence among all patients (N=200) Anemia present 137 (68.5%) 61.8%-74.5% χ²=27.38† <0.001* Anemia absent 63 (31.5%) 25.5%-38.2% Reference Severity among anemic patients (n=137) Mild anemia 41 (29.9%) 22.9%-38.1% Moderate anemia 67 (48.9%) 40.7%-57.2% χ²=16.53‡ <0.001* Severe anemia 29 (21.2%) 15.2%-28.7% Morphological pattern among anemic patients (n=137) Microcytic hypochromic 58 (42.3%) 34.4%-50.7% Normocytic normochromic 47 (34.3%) 26.9%-42.6% χ²=43.53§ <0.001* Macrocytic 23 (16.8%) 11.5%-23.9% Dimorphic 9 (6.6%) 3.5%-12.0% Red-cell indices among anemic patients (n=137) Haemoglobin, g/dL, Mean (SD) 9.47 (1.86) 9.16-9.78 One-sample t=−22.18¶ <0.001* Haematocrit, %, Mean (SD) 29.71 (5.84) 28.72-30.70 One-sample t=−16.62# <0.001* MCV, fL, Mean (SD) 82.64 (11.73) 80.66-84.62 One-sample t=2.63** 0.010* MCH, pg, Mean (SD) 27.18 (4.36) 26.44-27.92 One-sample t=−2.20†† 0.030* MCHC, g/dL, Mean (SD) 31.42 (2.37) 31.02-31.82 One-sample t=−7.80‡‡ <0.001* RDW-CV, %, Mean (SD) 17.86 (3.47) 17.27-18.45 One-sample t=13.02§§ <0.001* †Compared with a hypothesised anemia prevalence of 50%. ‡Goodness-of-fit test comparing the distribution of mild, moderate and severe anemia. §Goodness-of-fit test comparing the four morphological patterns. ¶Compared with haemoglobin of 13.0 g/dL. #Compared with haematocrit of 38%. **Compared with MCV of 80 fL. ††Compared with MCH of 28 pg. ‡‡Compared with MCHC of 33 g/dL. §§Compared with the upper normal RDW-CV value of 14%. Anemia was identified in 137 of the 200 patients, giving a prevalence of 68.5% (95% CI: 61.8%-74.5%). This prevalence was significantly higher than the hypothesised reference prevalence of 50% (χ²=27.38; p<0.001). Among the 137 anemic patients, moderate anemia was the most frequent severity category, affecting 67 (48.9%; 95% CI: 40.7%-57.2%) patients. Mild anemia was present in 41 (29.9%; 95% CI: 22.9%-38.1%) patients, whereas 29 (21.2%; 95% CI: 15.2%-28.7%) had severe anemia. The distribution of anemia severity differed significantly across these three categories (χ²=16.53; p<0.001), indicating a predominance of moderate anemia. Regarding morphology, microcytic hypochromic anemia was the most frequent pattern, observed in 58 (42.3%; 95% CI: 34.4%-50.7%) patients. Normocytic normochromic anemia was found in 47 (34.3%; 95% CI: 26.9%-42.6%), macrocytic anemia in 23 (16.8%; 95% CI: 11.5%-23.9%) and dimorphic anemia in 9 (6.6%; 95% CI: 3.5%-12.0%) patients. The distribution of morphological patterns was statistically significant (χ²=43.53; p<0.001). Thus, microcytic and normocytic patterns together accounted for more than three-fourths of anemia cases. The mean haemoglobin concentration among anemic patients was 9.47 ± 1.86 g/dL (95% CI: 9.16-9.78), which was significantly below the reference value of 13.0 g/dL (t=−22.18; p<0.001). The mean haematocrit was also significantly reduced at 29.71 ± 5.84% (p<0.001). The mean MCV was 82.64 ± 11.73 fL, while the mean MCH and MCHC were 27.18 ± 4.36 pg and 31.42 ± 2.37 g/dL, respectively. The significantly reduced MCH and MCHC supported the predominance of hypochromic anemia. RDW-CV was significantly elevated at 17.86 ± 3.47% compared with the upper reference value of 14% (t=13.02; p<0.001), indicating considerable variation in red-cell size and the possible coexistence of multiple nutritional or pathological mechanisms. Table 3. Association of anemia with aetiology, clinical manifestations, laboratory parameters and severity of chronic liver disease (N=200) Study parameter Anemia present (n=137) Anemia absent (n=63) Effect estimate (95% CI) Test of significance P value Aetiology of CLD Alcohol-associated liver disease 76 (55.5%) 27 (42.9%) OR: 1.66 (0.91-3.03) χ²=2.75 0.097 Chronic viral hepatitis 29 (21.2%) 18 (28.6%) OR: 0.67 (0.34-1.33) χ²=1.32 0.251 MASLD-related CLD 18 (13.1%) 11 (17.5%) OR: 0.72 (0.32-1.62) χ²=0.65 0.420 Autoimmune/cryptogenic/other 14 (10.2%) 7 (11.1%) OR: 0.91 (0.35-2.38) χ²=0.04 0.848 Clinical manifestations Previous gastrointestinal bleeding 49 (35.8%) 8 (12.7%) OR: 3.83 (1.69-8.69) χ²=11.27 0.001* Splenomegaly 73 (53.3%) 16 (25.4%) OR: 3.35 (1.73-6.48) χ²=13.59 <0.001* Ascites 86 (62.8%) 21 (33.3%) OR: 3.37 (1.80-6.32) χ²=15.04 <0.001* Hepatic encephalopathy 39 (28.5%) 6 (9.5%) OR: 3.78 (1.51-9.48) χ²=8.88 0.003* Clinical jaundice 92 (67.2%) 24 (38.1%) OR: 3.32 (1.79-6.18) χ²=14.96 <0.001* Esophageal/gastric varices 81 (59.1%) 19 (30.2%) OR: 3.35 (1.77-6.33) χ²=14.48 <0.001* Portal hypertensive gastropathy 51 (37.2%) 9 (14.3%) OR: 3.56 (1.62-7.81) χ²=10.81 0.001* Laboratory parameters Total bilirubin, mg/dL, Mean (SD) 4.76 (3.18) 2.41 (1.86) MD: 2.35 (1.65-3.05) Welch t=6.55 <0.001* Serum albumin, g/dL, Mean (SD) 2.63 (0.54) 3.24 (0.61) MD: −0.61 (−0.79 to −0.43) Welch t=−6.81 <0.001* INR, Mean (SD) 1.68 (0.39) 1.34 (0.27) MD: 0.34 (0.25-0.43) Welch t=7.14 <0.001* Platelet count, ×10³/µL, Mean (SD) 104.37 (48.26) 148.62 (57.41) MD: −44.25 (−60.57 to −27.93) Welch t=−5.31 <0.001* Serum creatinine, mg/dL, Mean (SD) 1.38 (0.62) 1.09 (0.43) MD: 0.29 (0.15-0.43) Welch t=3.83 <0.001* Severity of chronic liver disease Child-Pugh class A 25 (18.2%) 34 (54.0%) Reference Child-Pugh class B or C 112 (81.8%) 29 (46.0%) OR: 5.25 (2.72-10.15) χ²=26.48 <0.001* MELD score, Mean (SD) 17.82 (6.14) 11.46 (4.83) MD: 6.36 (4.79-7.93) Welch t=7.92 <0.001* Decompensated CLD 98 (71.5%) 26 (41.3%) OR: 3.58 (1.92-6.67) χ²=16.78 <0.001* Alcohol-associated liver disease was the most common aetiology among anemic patients, accounting for 55.5% of cases compared with 42.9% among non-anemic patients. However, this association was not statistically significant (OR=1.66, 95% CI: 0.91-3.03; p=0.097). Chronic viral hepatitis, MASLD-related CLD and autoimmune, cryptogenic or other causes also showed no statistically significant association with anemia. These findings suggest that anemia was not restricted to a particular aetiology of CLD and was more closely related to its clinical complications and severity. Previous gastrointestinal bleeding was significantly more frequent among anemic patients than non-anemic patients (35.8% versus 12.7%; OR=3.83, 95% CI: 1.69-8.69; p=0.001). Splenomegaly was present in 53.3% of anemic patients compared with 25.4% of non-anemic patients (OR=3.35, 95% CI: 1.73-6.48; p<0.001), suggesting a possible contribution of hypersplenism. Ascites was also significantly associated with anemia (62.8% versus 33.3%; OR=3.37, 95% CI: 1.80-6.32; p<0.001). Hepatic encephalopathy was nearly four times more likely among anemic patients (OR=3.78, 95% CI: 1.51-9.48; p=0.003). Similarly, clinical jaundice, esophageal or gastric varices and portal hypertensive gastropathy were significantly more common among anemic patients, with odds ratios of 3.32, 3.35 and 3.56, respectively. Laboratory findings demonstrated substantially poorer liver function among patients with anemia. Mean total bilirubin was significantly higher in anemic than non-anemic patients (4.76 ± 3.18 versus 2.41 ± 1.86 mg/dL; MD=2.35, 95% CI: 1.65-3.05; p<0.001). In contrast, mean serum albumin was significantly lower in the anemia group (2.63 ± 0.54 versus 3.24 ± 0.61 g/dL; MD=−0.61, 95% CI: −0.79 to −0.43; p<0.001). Anemic patients also had a higher mean INR (1.68 ± 0.39 versus 1.34 ± 0.27; p<0.001) and serum creatinine (1.38 ± 0.62 versus 1.09 ± 0.43 mg/dL; p<0.001). The mean platelet count was significantly lower among anemic patients (104.37 ± 48.26 versus 148.62 ± 57.41 ×10³/µL; MD=−44.25, 95% CI: −60.57 to −27.93; p<0.001), consistent with more severe portal hypertension and hypersplenism. Advanced liver disease showed a strong relationship with anemia. Child-Pugh class B or C was present in 81.8% of anemic patients compared with 46.0% of non-anemic patients. Patients in Child-Pugh classes B or C had more than five times the odds of anemia compared with patients in class A (OR=5.25, 95% CI: 2.72-10.15; p<0.001). The mean MELD score was significantly higher among anemic patients (17.82 ± 6.14 versus 11.46 ± 4.83; MD=6.36, 95% CI: 4.79-7.93; p<0.001). Decompensated CLD was likewise more frequent in the anemia group (71.5% versus 41.3%; OR=3.58, 95% CI: 1.92-6.67; p<0.001).

Table 1. Prevalence and clinical profile of anemia In the present study, anemia was detected in 137 of 200 patients with chronic liver disease, giving a prevalence of 68.5% (95% CI: 61.8%-74.5%). This finding closely agrees with Scheiner et al. (2020)[1], who reported anemia in 324 of 494 (66%) patients with advanced CLD and portal hypertension. Manrai et al. (2022)[2] similarly reported that anemia occurs in approximately 66%-75% of patients with cirrhosis. Paternostro et al. (2020)[3] found a somewhat lower prevalence of 52.9%; however, their study included both compensated and decompensated cirrhosis. In that study, anemia increased from 18.8% in compensated cirrhosis to 62.4% in decompensated cirrhosis. Differences in patient selection, disease severity, nutritional status, bleeding history and definitions of anemia may explain variation between studies. The mean age of anemic patients was higher than that of non-anemic patients, although the difference was marginally non-significant (49.28 versus 45.67 years; p=0.054). Male sex was also not significantly associated with anemia. Scheiner et al. (2020)[1] observed that the occurrence and severity of anemia were more closely related to hepatic dysfunction and portal hypertension than to demographic characteristics. Similarly, Dehghani et al. (2024)[4] found that the relationship between anemia and liver-disease severity was not explained by sex or the underlying cause of cirrhosis. Thus, the present findings suggest that anemia in CLD reflects disease progression and its complications rather than age or sex alone. The duration of CLD was significantly longer among anemic patients (5.84 versus 4.26 years; p<0.001). Longer disease duration provides greater opportunity for chronic inflammation, nutritional deficiency, recurrent gastrointestinal blood loss, hypersplenism and bone-marrow suppression to develop. Lingas (2023)[5] described anemia in cirrhosis as multifactorial, resulting from chronic blood loss, iron, folate or vitamin B12 deficiency, splenic sequestration, alcohol-related marrow toxicity and shortened erythrocyte survival. The significantly lower BMI among anemic patients (22.18 versus 23.46 kg/m²; p=0.017) may indicate poorer nutritional status. Nutritional depletion in cirrhosis can result from reduced dietary intake, early satiety due to ascites, malabsorption, altered metabolism and chronic systemic inflammation. These processes may produce iron, folate, vitamin B12 and protein deficiencies and thereby aggravate anemia. The European Association for the Study of the Liver (2018)[6] emphasised that malnutrition and muscle wasting are common in decompensated cirrhosis and are associated with an increased risk of complications. Alcohol consumption was more frequent among anemic patients, but its association was not statistically significant (OR=1.71; p=0.079). Alcohol may nevertheless contribute through direct suppression of erythropoiesis, folate deficiency, gastrointestinal bleeding and macrocytosis. The absence of statistical significance suggests that alcohol was not an independent determinant of anemia in this sample and that anemia occurred across all CLD aetiologies. Fatigue was reported by 81.0% of anemic patients compared with 49.2% of non-anemic patients (OR=4.41; p<0.001). Pallor showed the strongest relationship with anemia (OR=16.53; p<0.001), while exertional dyspnoea was also significantly more frequent (OR=3.55; p<0.001). These manifestations are biologically plausible consequences of reduced oxygen-carrying capacity. Nevertheless, fatigue in CLD may also result from inflammation, malnutrition, sleep disturbance and hepatic dysfunction; therefore, haemoglobin estimation remains necessary even when symptoms are non-specific. Pedal oedema, ascites and splenomegaly were each approximately three times more frequent among anemic patients. Splenomegaly may contribute to anemia through hypersplenism and increased sequestration and destruction of circulating blood cells. Ascites and oedema indicate impaired hepatic synthetic function and decompensation and may additionally produce haemodilution. Scheiner et al. (2020)[1] found that the severity of anemia increased with worsening hepatic dysfunction and portal hypertension. The multifactorial relationship between cytopenias, portal hypertension, hypersplenism and impaired hepatic function has also been highlighted by Lingas (2023)[5]. A previous history of gastrointestinal bleeding was significantly associated with anemia (OR=3.83; p=0.001). Chronic or recurrent bleeding from gastroesophageal varices, portal hypertensive gastropathy, gastric antral vascular ectasia or peptic lesions can progressively deplete iron stores and produce microcytic hypochromic anemia. Gjeorgjievski and Cappell (2016)[7] reported that portal hypertensive gastropathy may produce both acute and chronic gastrointestinal blood loss, with chronic bleeding commonly manifesting as iron-deficiency anemia. The present association between previous gastrointestinal bleeding and anemia supports blood loss as an important contributory mechanism. Decompensated CLD was observed in 71.5% of anemic patients compared with 41.3% of non-anemic patients (OR=3.58; p<0.001). This agrees closely with Paternostro et al. (2020)[3], who found a substantially higher prevalence of anemia in decompensated than compensated cirrhosis. Anemia in their cohorts was associated with a greater risk of subsequent hepatic decompensation or mortality. The relationship may be bidirectional: advanced liver disease causes anemia through bleeding, inflammation, nutritional deficiency and hypersplenism, whereas anemia may worsen systemic and hepatic tissue hypoxia. Table 2. Prevalence, severity and morphological patterns Moderate anemia was the most common severity category in the present study, affecting 48.9% of anemic patients, followed by mild anemia in 29.9% and severe anemia in 21.2%. The mean haemoglobin level was 9.47±1.86 g/dL. Scheiner et al. (2020)[1] reported that approximately two-thirds of patients with advanced CLD were anemic, although only about 7% had severe anemia below 8 g/dL. The higher proportion of severe anemia in the present study may reflect the relatively large proportion of patients with decompensated disease, previous gastrointestinal bleeding, varices and portal hypertensive gastropathy. Paternostro et al. (2020)[3] reported that anemia increased progressively across Child-Pugh classes, from 26.5% in class A to 59.2% in class B and 69.0% in class C. Ren et al. (2023)[8] also showed that severe anemia in patients hospitalised with cirrhosis was associated with poorer 90-day and one-year outcomes. Thus, the predominance of moderate-to-severe anemia in the present study is clinically important and may identify patients requiring evaluation for bleeding, nutritional deficiency, haemolysis and advanced hepatic dysfunction. Microcytic hypochromic anemia was the predominant morphological pattern, accounting for 42.3% of anemic patients, followed by normocytic normochromic anemia in 34.3%, macrocytic anemia in 16.8% and dimorphic anemia in 6.6%. The predominance of microcytic anemia is consistent with the high frequencies of gastrointestinal bleeding, gastroesophageal varices and portal hypertensive gastropathy in this study. Manrai et al. (2022)[2] noted that iron deficiency is one of the most frequent causes of anemia in cirrhosis and may arise from chronic gastrointestinal blood loss and inadequate dietary intake. Simbrunner et al. (2020)[9] demonstrated that portal hypertensive gastropathy was significantly associated with iron-deficiency anemia. Severe portal hypertensive gastropathy was associated with lower haemoglobin and a higher frequency of iron deficiency. Their results support the microcytic predominance observed in the present study. Gjeorgjievski and Cappell (2016)[7] similarly described chronic occult bleeding from portal hypertensive gastropathy as an important cause of microcytic hypochromic anemia. In contrast, Singh et al. (2020)[10] reported normocytic normochromic anemia in 51.4%, macrocytic anemia in 30.9%, microcytic anemia in 16.0% and dimorphic anemia in 1.7% of anemic cirrhotic patients. The higher proportion of microcytic anemia in the present study could be due to a greater burden of chronic gastrointestinal bleeding or iron deficiency. Differences in alcohol exposure, dietary patterns, severity of liver disease and laboratory definitions could also explain the variation. Normocytic anemia in 34.3% of the present patients may reflect chronic inflammation, hypersplenism, renal dysfunction, haemolysis or mixed nutritional deficiencies. Macrocytosis in 16.8% could have resulted from alcohol toxicity, folate or vitamin B12 deficiency, reticulocytosis and altered erythrocyte-membrane lipids. The mean MCV was within the broadly normocytic range, despite microcytic anemia being the largest individual morphological group. This apparent difference is possible because the overall mean was influenced by patients with macrocytosis and dimorphic anemia. MCH and MCHC were significantly reduced, supporting an important hypochromic component. The elevated mean RDW-CV of 17.86% indicated marked anisocytosis and may reflect iron deficiency, nutritional deficiency, recent blood loss, reticulocytosis or mixed anemia. Kalairajan et al. (2023)[11] observed significant associations of RDW with Child-Pugh and MELD scores and suggested that RDW may be a simple marker of CLD severity. Therefore, the elevated RDW in the present study may reflect both heterogeneous anemia and advanced liver dysfunction. Table 3. Association with aetiology, complications and severity Alcohol-associated liver disease was the most frequent aetiology among anemic patients, but neither alcohol-associated disease nor viral, MASLD-related or other aetiologies showed a statistically significant association with anemia. This suggests that anemia was principally related to the severity and complications of CLD rather than its initiating cause. Scheiner et al. (2020)[1] similarly found that anemia was linked to hepatic dysfunction and portal hypertension. Manrai et al. (2022)[2] emphasised that common final pathways including bleeding, inflammation, nutritional deficiency, hypersplenism and marrow suppression operate across different aetiologies. Gastrointestinal bleeding, splenomegaly, ascites, encephalopathy, jaundice, gastroesophageal varices and portal hypertensive gastropathy were all significantly associated with anemia. These findings represent a coherent clinical pattern of portal hypertension and hepatic decompensation. The association with varices and portal hypertensive gastropathy supports recurrent overt or occult blood loss. The Baveno VII consensus of de Franchis et al. (2022)[12] identifies ascites, variceal bleeding and hepatic encephalopathy as major consequences of clinically significant portal hypertension and disease decompensation. The AASLD guidance by Kaplan et al. (2024)[13] similarly emphasises the close relationship between clinically significant portal hypertension, varices and decompensating events. Portal hypertensive gastropathy was present in 37.2% of anemic patients compared with 14.3% of non-anemic patients (OR=3.56; p=0.001). Simbrunner et al. (2020)[9] found that iron-deficiency anemia and Child-Pugh score were independently associated with severe portal hypertensive gastropathy. This supports the likelihood that chronic subclinical mucosal bleeding contributed to the microcytic anemia observed in the present study. Anemic patients had significantly higher bilirubin, INR and serum creatinine but lower albumin and platelet counts. Higher bilirubin may indicate impaired hepatic clearance or increased red-cell destruction. Reduced albumin reflects impaired hepatic synthesis, systemic inflammation and poor nutritional status, while increased INR indicates deteriorating synthetic function. The lower platelet count is compatible with portal hypertension, splenic sequestration, reduced thrombopoietin synthesis and marrow suppression. Lingas (2023)[5] described these mechanisms as major contributors to haematological abnormalities in cirrhosis. The higher serum creatinine among anemic patients may indicate circulatory dysfunction, renal hypoperfusion or hepatorenal physiology in advanced CLD. Renal impairment can further aggravate anemia through reduced erythropoietin production and accumulation of inflammatory mediators. Therefore, the laboratory profile in the anemia group indicates multisystem involvement rather than an isolated reduction in haemoglobin. A particularly strong association was found between advanced Child-Pugh class and anemia. Child-Pugh class B or C was present in 81.8% of anemic patients compared with 46.0% of non-anemic patients, giving an OR of 5.25. The mean MELD score was also 6.36 points higher among anemic patients. Singh et al. (2020)[10] found a significant inverse correlation between haemoglobin and MELD score (r=−0.671; p<0.001), with the lowest haemoglobin levels among Child-Pugh class C patients. Paternostro et al. (2020)[3] likewise demonstrated a stepwise increase in anemia across Child-Pugh classes. The findings are also consistent with Scheiner et al. (2020)[1], who reported that the degree of hepatic dysfunction and portal hypertension correlated with anemia severity. Ren et al. (2023)[8] further demonstrated that severe anemia was associated with increased short- and long-term mortality among hospitalised cirrhotic patients. Overall, the present results indicate that anemia is not merely a coincidental laboratory abnormality but an important clinical marker of portal hypertension, hepatic decompensation, renal dysfunction, malnutrition and advanced CLD. However, because the present study was cross-sectional, temporal sequence and causality cannot be established.

Anemia was highly prevalent among patients with chronic liver disease, affecting 68.5% of the study population. Moderate anemia was the most frequent severity category, while microcytic hypochromic anemia was the predominant morphological pattern, followed by normocytic normochromic anemia. Anemia was significantly associated with a longer duration of liver disease, lower BMI, fatigue, pallor, exertional dyspnoea, pedal oedema, ascites, splenomegaly and previous gastrointestinal bleeding. Its prevalence did not differ significantly according to the underlying aetiology of CLD, suggesting that anemia was more closely related to disease progression and complications than to a specific cause. Anemic patients had higher bilirubin, INR, serum creatinine and MELD scores and lower serum albumin and platelet counts. Advanced Child-Pugh class, portal hypertensive complications and hepatic decompensation were strongly associated with anemia. Thus, anemia represents an important indicator of nutritional deficiency, portal hypertension and advanced hepatic dysfunction. Routine haematological assessment and timely evaluation for gastrointestinal blood loss, nutritional deficiencies, hypersplenism, renal dysfunction and other reversible causes should form an integral part of CLD management.

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