With global demographic shifts, the proportion of older adults is increasing markedly, and along with it the burden of age-related health conditions. The liver—though often resilient—undergoes structural, functional, and regenerative changes as part of the ageing process. These include reductions in liver volume, hepatocyte number, hepatic blood flow, and metabolic capacity, which together make the elderly more vulnerable to hepatic injury and slower recovery from insults [1, 2].

Liver diseases in the geriatric population—such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), autoimmune liver disease, and chronic viral hepatitis—often exhibit distinct histopathological patterns compared with younger adults [3]. Histological features such as hepatocellular ballooning, steatosis, inflammation, cholestasis, vascular alterations, and fibrosis are key to classifying the disease process and predicting outcomes [4, 5].

In older individuals, age-related hepatic alterations, including lipofuscin accumulation, sinusoidal pseudocapillarisation, diminished regenerative capacity, and increased extracellular matrix deposition, can alter or mask classic disease patterns [6, 7]. These changes may also modify the correlation between histological features and biochemical parameters, leading to atypical or subclinical disease presentation. Moreover, standard liver function tests (LFTs) can sometimes remain within normal limits despite advanced histopathological changes [8].

Given this complexity, studying histopathological patterns in elderly liver disease and their relationship with clinical and biochemical findings is essential. Such an approach can enhance understanding of the morphologic spectrum, identify correlations with biochemical derangements (e.g., elevated transaminases or cholestatic markers), and ultimately aid in early diagnosis and better prognostication [9].

The present study aims to analyse liver biopsy and autopsy specimens from elderly patients, identify predominant histopathological patterns, and correlate them with clinical and biochemical parameters to provide a comprehensive view of hepatic pathology in the ageing population.

This retrospective cross-sectional observational study was carried out in the Department of Pathology, at a tertiary care hospital, from January 2024 to September 2024, after obtaining approval from the Institutional Ethics Committee. All liver biopsy and autopsy specimens received during the study period were screened, and cases of patients aged 60 years and above with adequate tissue and complete clinical and biochemical information were included. Clinical data such as age, sex, symptoms, comorbidities like diabetes, hypertension, alcoholism, or viral hepatitis, and laboratory parameters including serum bilirubin, AST, ALT, alkaline phosphatase, total protein, albumin, and prothrombin time were retrieved from hospital records. Inadequate or autolyzed tissue samples and those with incomplete documentation or secondary metastatic involvement were excluded. The study thus comprised 58 elderly patients out of 146 liver specimens received in 2024, including 42 biopsy and 16 autopsy samples.

All specimens were fixed in 10 % neutral buffered formalin, routinely processed, and paraffin-embedded. Sections of 4–5 µm thickness were stained with hematoxylin and eosin, while special stains such as Masson’s trichrome, PAS, and reticulin were employed when required. Histopathological patterns were examined under light microscopy and categorized as non-alcoholic fatty liver disease, alcoholic liver disease, chronic viral hepatitis, autoimmune hepatitis, cirrhosis, cholestatic or drug-induced hepatitis, neoplastic lesions, or nonspecific reactive hepatitis. Grading and staging of inflammation and fibrosis were assessed using the Knodell Histological Activity Index or METAVIR scoring system where applicable. The histopathological patterns were correlated with the corresponding biochemical parameters to evaluate associations between morphological severity and biochemical derangements. All data were entered in Microsoft Excel 2024 and analyzed using SPSS version 26.0 (IBM Corp., USA). Descriptive statistics were used for demographic and biochemical variables, and associations between categorical data were analyzed using the Chi-square or Fisher’s exact test, while continuous variables were compared using Student’s t-test or ANOVA. A p-value < 0.05 was considered statistically significant.

Table 1. Demographic & Clinical Profile of Study Participants (n = 58)

In the present study comprising 58 elderly patients with liver disease, the majority (58.6%) belonged to the 60–69-year age group, followed by 31.0% in the 70–79-year group and 10.4% aged 80 years or above. Males predominated slightly (56.9%) over females (43.1%), reflecting a mild male preponderance in geriatric liver pathology. Among comorbid conditions, hypertension (50.0%) and diabetes mellitus (39.7%) were the most frequent, while alcohol use was reported in 25.9% of cases and viral hepatitis (HBV/HCV) in 20.7%.

Fig 1 – Age and Sex Distribution.

Clinically, jaundice was the most common presenting symptom, observed in 34.5% of patients, followed by nonspecific complaints such as fatigue, ascites, or hepatomegaly (not shown in table). These findings indicate that metabolic and lifestyle-related comorbidities, along with viral and alcohol-associated factors, play a significant role in the etiopathogenesis of liver diseases among the elderly.

Table 2. Distribution of Histopathological Patterns in Elderly Liver Specimens (n = 58)

Histopathological examination of 58 liver specimens from elderly patients revealed that non-alcoholic fatty liver disease (NAFLD/NASH) was the most prevalent pattern, accounting for 31.0% of cases, followed by alcoholic liver disease (ALD) in 20.7% and chronic viral hepatitis (HBV/HCV) in 17.2%. Cirrhosis represented 13.8%, reflecting the chronic progression of underlying hepatic injury.

Fig 2- Distribution Of Histopathological Patterns.

Less frequent findings included autoimmune hepatitis/primary biliary cholangitis (6.9%), drug-induced or cholestatic hepatitis (5.2%), and neoplastic lesions such as hepatocellular carcinoma or cholangiocarcinoma (5.2%). The predominance of NAFLD and ALD in this geriatric cohort underscores the rising contribution of metabolic and lifestyle-related liver diseases in the ageing population, while the continued presence of viral and autoimmune etiologies highlights the multifactorial nature of hepatic pathology in the elderly.

Table 3. Biochemical Parameters by Histopathological Category (Mean ± SD)

Analysis of biochemical parameters across different histopathological categories demonstrated distinct patterns corresponding to the severity of hepatic injury. Patients with cirrhosis showed the highest mean AST (110 ± 35 U/L) and ALP (220 ± 60 U/L) levels, accompanied by the most elevated serum bilirubin (2.4 ± 1.0 mg/dL) and lowest mean albumin concentration (3.2 ± 0.6 g/dL), reflecting advanced hepatic dysfunction and impaired synthetic capacity. In comparison, alcoholic liver disease and chronic viral hepatitis exhibited moderate elevations of transaminases and bilirubin with relatively preserved albumin levels. NAFLD/NASH cases showed milder biochemical abnormalities with AST and ALT values of 68 ± 22 U/L and 60 ± 18 U/L, respectively, and near-normal albumin levels (3.8 ± 0.4 g/dL). The overall trend indicated a progressive increase in AST and bilirubin and a decline in albumin with advancing histopathological severity, highlighting a strong correlation between biochemical derangement and structural liver damage in elderly patients.

Table 4. Grading & Staging of Inflammation and Fibrosis (n = 58)

Histological grading and staging of liver biopsies revealed that moderate inflammation (A2) was the most frequent finding, observed in 37.9% of cases, followed by mild inflammation (A1) in 34.5% of specimens. Correspondingly, fibrosis stages F2–F3 were the most prevalent, accounting for 41.4% of cases, while early-stage fibrosis (F0–F1) was seen in 20.7%. These observations suggest that a considerable proportion of elderly patients presented with established or bridging fibrosis, indicating chronicity of hepatic injury before clinical manifestation. The predominance of moderate inflammatory activity and advanced fibrosis highlights the cumulative impact of metabolic, alcoholic, and viral factors on hepatic architecture in the ageing population, reflecting delayed diagnosis or prolonged disease progression in many geriatric cases.

Table 5. Clinical Outcome by Histopathological Diagnosis (Follow-up/Autopsy Cases n = 58)

Follow-up and autopsy data revealed that clinical outcomes varied significantly with the underlying histopathological diagnosis. Among the cirrhosis cases, 50.0% showed progression to hepatic decompensation and 37.5% resulted in mortality, reflecting the advanced stage of disease at presentation. Patients with alcoholic liver disease also demonstrated a high rate of clinical deterioration, with 41.7% progressing to decompensation and 25.0% succumbing to complications, likely due to cumulative hepatotoxic effects and comorbid malnutrition. In contrast, NAFLD/NASH and chronic viral hepatitis groups exhibited relatively lower progression rates of 33.3% and 30.0%, and mortality rates of 11.1% and 10.0%, respectively. Overall, the findings emphasize that decompensation and mortality were most strongly associated with cirrhosis and alcohol-related pathology, highlighting the greater vulnerability of elderly patients with advanced fibrosis and multi-factorial hepatic injury.

Fig -3 Correlation Between Serum Bilirubin and Fibrosis.

The box-and-whisker plot illustrates a progressive increase in mean serum bilirubin levels with advancing fibrosis stages (F0–F4), indicating a significant positive correlation between biochemical and histological severity in elderly liver disease patients. The median bilirubin concentration rose from approximately 1.0 mg/dL in early fibrosis (F0–F1) to nearly 2.6 mg/dL in advanced cirrhosis (F4). This trend reflects declining hepatic excretory and synthetic function with the progression of structural fibrosis. Statistical analysis using ANOVA revealed a significant association (p < 0.05) between serum bilirubin levels and fibrosis stages, demonstrating that bilirubin serves as a sensitive biochemical indicator of disease progression in the geriatric population.

In this study of 58 geriatric patients with liver disease, our findings highlight a significant burden of metabolic- and lifestyle-related hepatic pathology, with Non‑Alcoholic Fatty Liver Disease/NASH (31.0%) and alcoholic liver disease (20.7%) together comprising over half of the histopathological diagnoses. This mirrors broader epidemiological trends in older adults, where metabolic syndrome, insulin resistance, diabetes and hypertension drive steatosis progression and hepatic injury [8]. Aging itself brings structural and functional changes in the liver—reduced hepatic blood flow, decreased regenerative capacity, increased extracellular matrix deposition—which predispose older livers to worse outcomes when stressed by injury [9].

Our histopathological spectrum corroborates the notion that the elderly present with more advanced disease at diagnosis: for example, the proportion of cases with moderate to severe fibrosis (F2–F3) was 41.4% and cirrhosis accounted for 13.8%. This is consistent with literature showing that elderly patients with NAFLD, for instance, have a higher prevalence of advanced fibrosis compared with younger cohorts (35.4% vs. 13.3%) [10]. The strong correlation in our cohort between elevated biochemical parameters (e.g., bilirubin, AST) and higher fibrosis stage aligns with mechanistic studies demonstrating age-related hepatocyte senescence, stellate cell activation and macrophage polarization that accelerate fibrogenesis in aging livers [11].

Furthermore, the comorbidity profile in our subjects (diabetes 39.7%, hypertension 50.0%, alcohol use 25.9%) reflects the multi-hit pathogenesis of geriatric liver disease: the interplay of metabolic insults, vascular disease, chronic viral or alcohol injury, and age-associated hepatic vulnerability. Aging processes such as mitochondrial dysfunction and proteostasis decline contribute to impaired clearance of injury and greater fibrotic response [8]. The clinical outcome data in our study – with highest decompensation (50%) and mortality (37.5%) in the cirrhosis group – underscore that older age is not just a backdrop but an amplifier of poor prognosis in chronic liver disease [12].

Our study thus underscores several important implications for practice. First, in geriatric patients, early liver disease may be more silent and yet more advanced at presentation; simple liver tests may underestimate underlying fibrotic burden. Second, management approaches tailored to younger adults may not be sufficient; for instance, non-invasive fibrosis scores appear less specific in older persons [10]. Third, the high prevalence of metabolic comorbidity in this age-group highlights the need for integrated care targeting diabetes, hypertension and lifestyle factors alongside hepatology input. Finally, pathologists and clinicians should recognize that in the elderly, histopathology often reveals advanced fibrosis even when biochemical derangement is modest—thus reinforcing the value of tissue diagnosis or advanced imaging when indicated.

Limitations of our study include its single-centre, retrospective nature and the relatively small sample size. Moreover, while our histopathological categorisation and biochemical correlation provide meaningful insights, longitudinal follow-up data were limited. Future multicentre studies with larger elderly cohorts and standardized histopathological scoring will help refine age-specific diagnostic and prognostic models. Research into therapeutic interventions in older patients—who often have poly-morbidities and reduced physiological reserve—is also urgently needed [12].

The present study highlights that liver diseases in the elderly predominantly arise from metabolic and lifestyle-related causes such as NAFLD/NASH and alcoholic liver disease, with a considerable proportion presenting with moderate to advanced fibrosis at the time of diagnosis. The close correlation observed between biochemical abnormalities—particularly elevated serum bilirubin, AST, and ALP—and higher histopathological grades of inflammation and fibrosis underscores the importance of integrating biochemical and morphological assessment for accurate disease staging. Advancing age not only alters the histological response of the liver to injury but also compounds disease progression due to comorbidities like diabetes and hypertension. These findings emphasize that in geriatric patients, liver pathology often reflects a chronic, multifactorial process with a tendency toward fibrosis and cirrhosis, even when biochemical parameters appear only moderately deranged. Early recognition through targeted screening, timely histopathological evaluation, and comprehensive management of metabolic risk factors are crucial for improving outcomes in this vulnerable population.

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