An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations

Abstract

Background: In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.

Methods: A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.

Results: Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.

Conclusions: The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

Figure 1. Distribution of the patients admitted at INEN with HCC from January 1997 to December 2010.

Histograms show the distribution of patients over the period in function of their diagnosis date (A), age at the time of diagnosis (B,C), and gender (C). X-axes display date (annual interval) (A) and age (3-year interval) (B,C); Y-axes display fraction (A,B) and frequency (Freq) (C) of the total number of patients (N = 1,541). Straight line represents the histogram curve fitting with a Gaussian mixture function (BI = 1.95; MM: 44.8) (B). Female and male patients are represented in light and dark greys, respectively (C).

Figure 2. Pathophysiological parameters associated with HCC in the two age-based patient populations.

(A) Box plots show quartile distribution of seroAFP in ng/ml in ≤44 group (grey box; N = 631) and >44 group (black box; N = 558). *P<0.0001 vs. >44 group (i.e. adjusted multiple linear regression analysis). (B) Estimated fractions (%) of HCC attributable to HBV and HCV etiologies (VirEtiol) or non-viral cirrhosis (CIR), or non-attributable to bona fide risk factor (ND) in ≤44 females (hatched grey) and males (solid grey) and >44 females (hatched black) and males (solid black). (C) Overall Kaplan–Meier survival curve for patients selected for anatomic liver resection (N = 298). (D) Age-based Kaplan–Meier survival curves for the ≤44 group (grey curve; N = 156) and the >44 group (black curve; N = 139). (E) Kaplan–Meier survival rates (%) monitored for the 2 age-based populations at 1, 3, and 5 years following hepatectomy. Median survival is presented as month (upper – lower interquartile range).

Figure 3. Regional disparities in mean age of Peruvian patients with HCC.

The map was generated using the incidence rates of patients admitted at INEN with HCC between 1997 and 2010. The regions are classified as follow: (1) Amazonas (N = 20; mean age: 36.2±20.3); (2) Ancash (N = 117; 49.7±22.3); (3) Apurimac (N = 121; 31.6±17.9); (4) Arequipa (N = 39; 56.6±22.3); (5) Ayacucho (N = 161; 39.5±20.6); (6) Cajamarca (N = 36; 50.2±19.4); (7) Callao (N = 21; 52.3±20.7); (8) Cuzco (N = 96; 33.8±16.6); (9) Huancavelica (N = 32; 45.3±23.9); (10) Huanuco (N = 68; 37.2±20.8); (11) Ica (N = 43; 56.1±19.3); (12) Junin (N = 180; 37.2±19.9); (13) La Libertad (N = 68; 61.6±19.3); (14) Lambayeque (N = 53; 56.8±19.8); (15) Lima (N = 289; 48±21.5); (16) Loreto (N = 21; 42.7±20.8); (17) Madre de Dios (N = 2; ND); (18) Moquegua (N = 5; ND); (19) Pasco (N = 29; 47.3±19.6); (20) Piura (N = 64; 58.2±18.5); (21) Puno (N = 18; 55.4±13.7); (22) San Martin (N = 26; 43.3±19.6); (23) Tacna (N = 4; ND); (24) Tumbes (N = 3; ND); and (25) Ucayali (N = 25; 38.2±18.8). Mean age intervals (years) are established as follow: – (dark blue); – (light blue); – (yellow); – (pink); and [53–62] (red). ND: Mean age was not determined because the cohort of patients admitted at INEN during the period and originating from these regions was too small. Administrative regional limits from the Peruvian National Institute of Statistics and Informatics (INEI).