Letters to the Editor
Surveillance for Hepatocellular Carcinoma in Alcoholic Patients Paolo Borro, MD1 and Gianni Testino, MD1 doi:10.1038/ajg.2013.296
To the Editor: we have read the excellent letter to the editor by Giannini and Trevisani (1). The Authors do not agree with Singal et al.’ (2) consideration for reintroducing serum alpha-feto-protein (AFP) in the surveillance armamentarium for hepatocellular carcinoma (HCC). Alcohol has been recently inserted in the Group 1 International Agency for Research on Cancer (IARC—World Health Organization). It has been confirmed a causal link between alcohol consumption and HCC. In Europe among men and women, 33% (11–54%) and 18% (3–38%) of the incidence of the total HCC was attributable to former and current alcohol consumption (3). Moreover, a meta-analysis suggests that the risk of liver cancer does indeed fall after cessation by 6–7% a year. It is estimated that a time period of 23 years is required after drinking cessation, with a correspondingly large 95% confidence interval of 14–70 years, for the risk of liver cancer to be equal to that of never drinkers (4). It emerges the necessity of a strict follow-up every 6 or 12 months in relation with the clinical features of the alcoholic patients. In our Regional Alcoholic Unit in 2012, we identified 12 HCC in Child A alcoholic cirrhosis (four females, average age: 55±6.5) without viral infection. The identification was effected with ultrasound and confirmed with contrastenhanced ultrasound. All nodules were identified with a diameter inferior to 3 cm. Eleven patients had AFP in the normal range (1–8 ng/ml). In one patient the value was 15 ng/ml. © 2013 by the American College of Gastroenterology
Successively, the patients were treated with resection or percutaneous ablation. The role of AFP in the diagnosis and surveillance of HCC has decreased during the past few years. The cut-off usually found to be useful in discriminating between highand low-risk groups has been 20 ng/ml. In the experience of Mancebo et al. (5), only three patients (3/62: 4.8%) had baseline AFP values greater than 20 ng/ml and for that reason it is not surprising that the initial value of AFP had not been found to be a risk factor for HCC. It seems to suggest that baseline AFP level could have a role as a predictive factor for HCC in viral cirrhosis, but not in the case of alcoholic cirrhosis. In our opinion, the combined use of ultrasound and serum AFP has both direct and indirect costs for each early detection of HCC, which are too expensive. According to Giannini and Trevisani, (1) there is evidence that a well-conducted surveillance based on ultrasound performed by expert operator can detect most HCCs at an early stage. Therefore, in our opinion ultrasound performed by expert is sufficient if the operator is also an experted hepatologist. CONFLICT OF INTEREST
The authors declare no conflict of interest. REFERENCES 1. Giannini EG, Trevisani F. Surveillance for hepatocellular carcinoma: just do it!. Am J Gastroenterol 2013;108:1013–4. 2. Singal AG, Yopp A, Skinner S et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol 2013; 108:425–32. 3. A review of human carcinogens. World Health Organization, International Agency for Research on Cancer 2012;100 (Part E): 373–499. 4. Heckley GA, Jarl J, Asamoah BO et al. How the risk of liver cancer changes after alcohol cessation: a review and meta-analysis of the current literature. BMC Cancer 2011;11:446–55. 5. Mancebo A, Gonzalez-Dieguez ML, Cadahia V et al. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk group. Clin Gastroenterol Hepatol 2013;11:95–101. 1
Alcohol Unit, Department of Internal and Specialistic, Medicine, IRCCS AOU San MartinoIST, Genova, Italy. Correspondence: Paolo Borro, MD, Alcohol Unit, Department of Internal and Specialistic, Medicine, IRCCS AOU San Martino-IST, 16035 Genova, Italy. E-mail: [email protected]
The Routine Use of Fecal Calprotectin in Clinical Pediatric Practice: Almost there or Still Issues to Address? Gabrielle Bourdillon, MSc, BSc1, Olga Biskou, MSc, BSc1, Mary MacKinder, MSc, BSc1, Muhammad Jaffar Khan, MBBS, PGDEBM1, Melina Tsiountsioura, MSc, BSc1, Clare Clark, MSc, BSc1, Richard K. Russell, PhD, MBChB2, Paraic McGrogan, MBChB2, Christine Ann Edwards, PhD, BSc1 and Konstantinos Gerasimidis, PhD, MSc, BSc, PGCAP1,2 doi:10.1038.ajg.2013.213
To the Editor: The pivotal role of fecal calprotectin (FC) in screening for suspected pediatric inflammatory bowel disease (IBD) has been robustly reinforced by the recent meta-analysis while concurrently raising other intriguing points worthy of further consideration (1). The low specificity of FC in children is especially noteworthy and could suggest a larger biological variation of FC in children than in adults. Thus, an age-specific reference range may be more appropriate to improve diagnostic validity and reduce unnecessary clinical interventions in children. Also while the diagnostic validity of FC in naive IBD is well established, there are limited data on children with clinically quiescent disease and the threshold for portraying overt clinical symptoms. Furthermore, there is the continuous development of new FC kits where the issue of inter-kit variability also need to be evaluated. We measured FC in 121 individuals: 67 healthy children (4–16 years), 24 children with established CD (8–15 years, 12 with clinically quiescent disease), and 30 healthy adults (24–57 years), using two ELISA kits from the same manufacturer CalproLab (CALP0170) and Calpro (CAL0100). Using CalproLab healthy children had higher median FC than adults (P = 0.021). Seven percent of adults and 22% of healthy The American Journal of GASTROENTEROLOGY
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Surveillance for Hepatocellular Carcinoma in Alcoholic Patients Paolo Borro, MD1 and Gianni Testino, MD1 doi:10.1038/ajg.2013.296
To the Editor: we have read the excellent letter to the editor by Giannini and Trevisani (1). The Authors do not agree with Singal et al.’ (2) consideration for reintroducing serum alpha-feto-protein (AFP) in the surveillance armamentarium for hepatocellular carcinoma (HCC). Alcohol has been recently inserted in the Group 1 International Agency for Research on Cancer (IARC—World Health Organization). It has been confirmed a causal link between alcohol consumption and HCC. In Europe among men and women, 33% (11–54%) and 18% (3–38%) of the incidence of the total HCC was attributable to former and current alcohol consumption (3). Moreover, a meta-analysis suggests that the risk of liver cancer does indeed fall after cessation by 6–7% a year. It is estimated that a time period of 23 years is required after drinking cessation, with a correspondingly large 95% confidence interval of 14–70 years, for the risk of liver cancer to be equal to that of never drinkers (4). It emerges the necessity of a strict follow-up every 6 or 12 months in relation with the clinical features of the alcoholic patients. In our Regional Alcoholic Unit in 2012, we identified 12 HCC in Child A alcoholic cirrhosis (four females, average age: 55±6.5) without viral infection. The identification was effected with ultrasound and confirmed with contrastenhanced ultrasound. All nodules were identified with a diameter inferior to 3 cm. Eleven patients had AFP in the normal range (1–8 ng/ml). In one patient the value was 15 ng/ml. © 2013 by the American College of Gastroenterology
Successively, the patients were treated with resection or percutaneous ablation. The role of AFP in the diagnosis and surveillance of HCC has decreased during the past few years. The cut-off usually found to be useful in discriminating between highand low-risk groups has been 20 ng/ml. In the experience of Mancebo et al. (5), only three patients (3/62: 4.8%) had baseline AFP values greater than 20 ng/ml and for that reason it is not surprising that the initial value of AFP had not been found to be a risk factor for HCC. It seems to suggest that baseline AFP level could have a role as a predictive factor for HCC in viral cirrhosis, but not in the case of alcoholic cirrhosis. In our opinion, the combined use of ultrasound and serum AFP has both direct and indirect costs for each early detection of HCC, which are too expensive. According to Giannini and Trevisani, (1) there is evidence that a well-conducted surveillance based on ultrasound performed by expert operator can detect most HCCs at an early stage. Therefore, in our opinion ultrasound performed by expert is sufficient if the operator is also an experted hepatologist. CONFLICT OF INTEREST
The authors declare no conflict of interest. REFERENCES 1. Giannini EG, Trevisani F. Surveillance for hepatocellular carcinoma: just do it!. Am J Gastroenterol 2013;108:1013–4. 2. Singal AG, Yopp A, Skinner S et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol 2013; 108:425–32. 3. A review of human carcinogens. World Health Organization, International Agency for Research on Cancer 2012;100 (Part E): 373–499. 4. Heckley GA, Jarl J, Asamoah BO et al. How the risk of liver cancer changes after alcohol cessation: a review and meta-analysis of the current literature. BMC Cancer 2011;11:446–55. 5. Mancebo A, Gonzalez-Dieguez ML, Cadahia V et al. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk group. Clin Gastroenterol Hepatol 2013;11:95–101. 1
Alcohol Unit, Department of Internal and Specialistic, Medicine, IRCCS AOU San MartinoIST, Genova, Italy. Correspondence: Paolo Borro, MD, Alcohol Unit, Department of Internal and Specialistic, Medicine, IRCCS AOU San Martino-IST, 16035 Genova, Italy. E-mail: [email protected]
The Routine Use of Fecal Calprotectin in Clinical Pediatric Practice: Almost there or Still Issues to Address? Gabrielle Bourdillon, MSc, BSc1, Olga Biskou, MSc, BSc1, Mary MacKinder, MSc, BSc1, Muhammad Jaffar Khan, MBBS, PGDEBM1, Melina Tsiountsioura, MSc, BSc1, Clare Clark, MSc, BSc1, Richard K. Russell, PhD, MBChB2, Paraic McGrogan, MBChB2, Christine Ann Edwards, PhD, BSc1 and Konstantinos Gerasimidis, PhD, MSc, BSc, PGCAP1,2 doi:10.1038.ajg.2013.213
To the Editor: The pivotal role of fecal calprotectin (FC) in screening for suspected pediatric inflammatory bowel disease (IBD) has been robustly reinforced by the recent meta-analysis while concurrently raising other intriguing points worthy of further consideration (1). The low specificity of FC in children is especially noteworthy and could suggest a larger biological variation of FC in children than in adults. Thus, an age-specific reference range may be more appropriate to improve diagnostic validity and reduce unnecessary clinical interventions in children. Also while the diagnostic validity of FC in naive IBD is well established, there are limited data on children with clinically quiescent disease and the threshold for portraying overt clinical symptoms. Furthermore, there is the continuous development of new FC kits where the issue of inter-kit variability also need to be evaluated. We measured FC in 121 individuals: 67 healthy children (4–16 years), 24 children with established CD (8–15 years, 12 with clinically quiescent disease), and 30 healthy adults (24–57 years), using two ELISA kits from the same manufacturer CalproLab (CALP0170) and Calpro (CAL0100). Using CalproLab healthy children had higher median FC than adults (P = 0.021). Seven percent of adults and 22% of healthy The American Journal of GASTROENTEROLOGY
1811
