Advanced Hepatocellular Carcinoma in India Is Strongly Associated with Poor Surveillance: A Multicentre Study of 1,599 Patients.

Technical Summary: Advanced Hepatocellular Carcinoma in India Is Strongly Associated with Poor Surveillance

Problem Statement
In India, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, severely limiting curative treatment options. While guidelines from the Indian National Association for the Study of Liver disease recommend semi-annual surveillance using liver ultrasound (US) and serum alpha-fetoprotein (AFP) for patients with known cirrhosis, there is a lack of large-scale, real-world data quantifying adherence to these recommendations. Furthermore, the relationship between the failure to recognize underlying cirrhosis and the subsequent lack of surveillance remains unexplored in the Indian context. This study addresses the gap in understanding how surveillance practices and the recognition of chronic liver disease correlate with the stage of HCC at diagnosis.

Methodology
This was a multicentre, retrospective study conducted between July 2023 and December 2025, involving 34 institutions across India. The study cohort consisted of 1,599 consecutive patients diagnosed with HCC, recruited by 99 trained gastroenterologists and hepatologists.

• Data Collection: A standardized electronic questionnaire was used to collect data on prior recognition of cirrhosis, surveillance practices (US and AFP within 6 months prior to diagnosis), and tumor staging.
• Definitions: HCC diagnosis was confirmed via LI-RADS score 4 or 5 on CT/MRI or characteristic liver biopsy. "Early HCC" was defined as disease falling within the Milan criteria.
• Statistical Analysis: Categorical variables were compared using Chi-square tests, while continuous variables were analyzed using Student's t-test or Mann–Whitney U tests. A stepwise multivariable logistic regression was performed to identify independent predictors of early-stage HCC (within Milan criteria). Model performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUC).

Key Results

• Surveillance Uptake: Adherence to surveillance guidelines was critically low. Only 35% of patients had been advised to undergo surveillance. Actual testing rates within 6 months of diagnosis were 16% for ultrasound and 12% for AFP.
• Cirrhosis Recognition: Only 45% of patients (726/1599) had a known diagnosis of cirrhosis prior to their HCC diagnosis.
• Stage at Diagnosis: Only 41% of the total cohort presented with HCC within the Milan criteria.
• Correlation with Surveillance: Patients presenting within the Milan criteria were significantly more likely to have received prior surveillance advice (54% vs. 22%, p<0.001), undergone US (26% vs. 9%, p<0.001), and undergone AFP testing (21% vs. 6%, p<0.001) compared to those outside the Milan criteria.
• Correlation with Cirrhosis: Prior recognition of cirrhosis was significantly higher in patients within the Milan criteria (63%) compared to those outside (33%, p<0.001).
• Predictors of Early Detection: Multivariable logistic regression identified three independent predictors of HCC within the Milan criteria:
  1. Prior advice for surveillance (OR 2.20).
  2. Prior performance of AFP testing (OR 2.00).
  3. Prior diagnosis of cirrhosis (OR 1.98).
     The model demonstrated moderate discrimination with an AUC of 0.69 and an overall accuracy of 68%.
• AFP Utility: Single AFP measurements did not reliably discriminate between early and advanced disease. While higher AFP thresholds showed a trend toward lower odds of being within Milan criteria, these differences were not statistically significant.

Significance and Claims
The authors claim this is the largest real-world dataset from India and the first to demonstrate a strong association between surveillance practices and the detection of HCC within the Milan criteria in a large Indian cohort.

The study concludes that the late presentation of HCC in India is driven primarily by two systemic failures:

1. Poor recognition of cirrhosis: A significant portion of the population with underlying liver disease remains undiagnosed, preventing them from entering surveillance programs.
2. Low adherence to surveillance: Even among those with known cirrhosis, the uptake of recommended semi-annual US and AFP testing is low.

The paper posits that strengthening the early detection of chronic liver disease and improving adherence to surveillance recommendations could substantially increase the proportion of patients eligible for curative therapy. The authors explicitly state that while the study is representative of current practices, it is retrospective and requires confirmation via prospective studies. They also note that cost-effectiveness analyses and public health policy implications warrant further evaluation.