- Email: [email protected]
Reply to: “Scoring system in diagnosing biliary atresia”
Letters to the Editor reassessed with or without incorporation of PEHS and with or without removal of liver biopsy in a large study. In addition, there seems an error in the manuscript; the cut-off value may be ‘‘31.164’’, not ‘‘311.644’’ in Fig. 1C and D.
Conflict of interest The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] El-Guindi MA, Sira MM, Sira AM, Salem TA, El-Abd OL, Konsowa HA, et al. Design and validation of a diagnostic score for biliary atresia. J Hepatol 2014;61:116–123. [2] Kianifar HR, Tehranian S, Shojaei P, Adinehpoor Z, Sadeghi R, Kakhki VR, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol 2013;43:905–919. [3] Kwatra N, Shalaby-Rana E, Narayanan S, Mohan P, Ghelani S, Majd M. Phenobarbital-enhanced hepatobiliary scintigraphy in the diagnosis of biliary atresia: two decades of experience at a tertiary center. Pediatr Radiol 2013;43:1365–1375.
[4] Liu SX, Huang ZH. The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice. Front Med China 2010;4:342–345. [5] Lin WY, Lin CC, Changlai SP, Shen YY, Wang SJ. Comparison technetium of Tc-99m disofenin cholescintigraphy with ultrasonography in the differentiation of biliary atresia from other forms of neonatal jaundice. Pediatr Surg Int 1997;12:30–33. [6] Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology 2009;49:1017–1044.
⇑
Rui Dong Shan Zheng Department of Pediatric Surgery, Children’s Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China ⇑Corresponding author. Address: Department of Pediatric Surgery, Children’s Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health, 399 Wan Yuan Road, Shanghai 201102, China. Tel.: +86 021 64931007; fax: +86 021 64931901. E-mail address: [email protected]
Reply to: ‘‘Scoring system in diagnosing biliary atresia’’ To the Editor: We appreciate the interest of Dong and Zheng in our recent study [1]. Although hepatobiliary scintigraphy (HBS) is one of the most sensitive methods for the diagnosis of biliary atresia (BA), it has a low specificity (70.4%) as reported in a meta-analysis of 81 studies [2]. Sun et al. [3] reported a 13.3% (66/498) false positive rate of HBS. They concluded that the excessive dependence on HBS may contribute to the misdiagnosis of BA. Although HBS, showing biliary excretion, excludes BA, non-excretion neither confirms the diagnosis of BA nor rules out the diagnosis of non-BA aetiologies [4]. Oral phenobarbital can enhance the diagnostic performance of HBS by re-examination one week later [5]; however, for the potential delay in diagnosis it is not routinely practiced [6]. Moreover, the reported BA score specificity (97.67%) [1] cannot be enhanced by HBS, which has a much lower specificity [2]. Liu and Huang [5] reported that if no bile was found in the duodenal tube test (DTT), the drainage tube would be kept for up to 72 h. In some cases, the duodenal fluid changed from white to yellow after several days or weeks. Therefore, persistent examination of the duodenal fluid is very important. This also prolongs the time of diagnosis and is not routinely performed. However, DTT may have a special importance in situations where other tests are not available [6]. An important concept of our BA score [1] is that it depends on parameters that are an integral part of the workup and are routinely performed for patients suffering neonatal cholestasis (NC) whether suspected to be BA or non-BA. Contrarily, HBS and DTT cannot be considered as such. Dong and Zheng were encouraged by the article of Liu and Huang [5] that reports a performance of combined HBS and
DTT of 100% sensitivity and 100% specificity. We read the article with great interest but we found two major concerns. First, recruitment of patients was selective as patients with certain aetiologies were excluded from the study. This selectivity may render the calculated specificity inaccurately a representative one. Furthermore, it supports the concept that these procedures are needed for selected patients. Second, the method of calculating the combined performance is not clear. According to their results, 3 groups of patients can be discriminated: (1) Patients having HBS with no excretion and DTT with no bile; (26 patients with BA). (2) Patients having HBS with excretion and DTT with bile; (41 patients with non-BA). (3) Patients having HBS with no excretion and DTT with bile; (17 patients; 3 were BA and 14 were non-BA). These results can never, in any way, lead to a sensitivity and specificity of 100%. It seems that Liu and Huang [5] simply combined the sensitivity of one test (HBS) with the specificity of the other (DTT) which is unreasonable. Dong and Zheng, suggested that liver biopsy should be avoided whenever possible. We disagree with this concept as we believe that liver biopsy should be performed unless there is a contraindication or when parents refuse the procedure. For that, liver biopsy is considered as an integral part of the diagnostic workup of NC patients and is strongly encouraged according to ‘‘The Cholestasis Guideline Committee’’ of the NASPGN [7]. The aim of liver biopsy in NC is not only to evaluate the features of biliary outflow obstruction but is also an essential tool in revealing the aetiology of the liver disease, and in assessing the fibrosis stage which affects treatment policy. Such targets are irreplaceable by HBS and DTT. For that, liver biopsy is generally considered the ‘‘gold standard’’ compared to other diagnostic
Open access under CC BY-NC-ND license.
1442
Journal of Hepatology 2014 vol. 61 j 1438–1452
JOURNAL OF HEPATOLOGY tools [8]. Recently, Boskovic et al. [9] reported that liver biopsy was superior to DTT in the diagnosis of BA. As for the safety of liver biopsies, Pietrobattista et al. [10] raised the issue asking ‘‘Is juvenile liver biopsy unsafe?’’ They concluded that ultrasound-guided biopsy, performed in a specialized tertiary care paediatric centre by an experienced physician, is considered safe; which is the same in our experience. Although the study population in our study was relatively small, yet, when compared to the studies (discussed in our article) of Chiba and Kasai as well as Gupta et al., evaluating different scores for discriminating BA, our study population was still relatively high [1] (population size was 123, 120 and 135, respectively). Nonetheless, we suggest that the score needs to be validated in different populations with different investigators. The numbers in Fig. 1C and D [1] represent the values of the odds ratio (OR) model. For a parameter like hepatic subcapsular flow, which was found in 29/30 of BA and in 1/30 of the nonBA (Table 3), the OR equals 841. The regression coefficient for the same parameter was 6.735 and the relative risk was 29. This clarifies the higher values in the OR model compared to other models. So, we affirm that there is no mistake.
Conflict of interest The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] El-Guindi MA, Sira MM, Sira AM, Salem TA, El-Abd OL, Konsowa HA, et al. Design and validation of a diagnostic score for biliary atresia. J Hepatol 2014;61:116–123. [2] Kianifar HR, Tehranian S, Shojaei P, Adinehpoor Z, Sadeghi R, Kakhki VR, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol 2013;43:905–919.
[3] Sun S, Chen G, Zheng S, Xiao X, Xu M, Yu H, et al. Analysis of clinical parameters that contribute to the misdiagnosis of biliary atresia. J Pediatr Surg 2013;48:1490–1494. [4] Yachha SK. Cholestatic jaundice during infancy. Indian J Gastroenterol 2005;24:47–48. [5] Liu SX, Huang ZH. The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice. Front Med China 2010;4:342–345. [6] Jain AK. Approach to cholestatic Jaundice in newborn. In: Sachdeva A, Dutta AK, Jain MP, Satya PY, Goyal RK, Arora A, et al., editors. Advances in pediatrics. Daryaganj, New Delhi, India: Jaypee brothers Medical publishers (P) Ltd; 2012. p. 126–132. [7] Moyer V, Freese DK, Whitington PF, Olson AD, Brewer F, Colletti RB, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004;39:115–128. [8] Yeh MM. Pathologic diagnosis of biliary atresia on liver biopsy: is tissue the issue? J Gastroenterol Hepatol 2009;24:936–938. [9] Boskovic A, Kitic I, Prokic D, Stankovic I, Grujic B. Predictive value of hepatic ultrasound, liver biopsy, and duodenal tube test in the diagnosis of extrahepatic biliary atresia in Serbian infants. Turk J Gastroenterol 2014;25:170–174. [10] Pietrobattista A, Fruwirth R, Natali G, Monti L, Devito R, Nobili V. Is juvenile liver biopsy unsafe? Putting an end to a common misapprehension. Pediatr Radiol 2009;39:959–961.
Mohamed Abdel-Salam El-Guindi ⇑ Mostafa Mohamed Sira Ahmad Mohamed Sira Tahany Abdel-Hameed Salem Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya, Egypt ⇑Corresponding author. Address: Department of Pediatric Hepatology, National Liver Institute, Menofiya University, 32511 Shebin El-koom, Menofiya, Egypt. Tel.: +20 48 222 2740; fax: +20 48 223 4586. E-mail address: [email protected]
AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis To the Editor: We read with great interest the study by Trivedi, Bruns and colleagues [1] on the association between the AST/platelet ratio index (APRI) and long-term transplant-free survival in patients with primary biliary cirrhosis (PBC). The authors demonstrated that elevated APRI (>0.54) at diagnosis and/or 1 year afterward (APRI-1y) was significantly associated with a future risk of adverse events independently and additively of the ursodeoxycholic acid (UDCA) therapy response, using a deviation cohort from the Elizabeth Hospital, Birmingham (UK), and a validation cohort from the Toronto Center for Liver Diseases (Canada) and the Jena University Hospital (Germany). Since APRI is a simple, widely studied, non-invasive, and easily calculated marker of
liver disease, it represents a useful tool in clinical practice, especially at outpatient clinics, to assess patient prognosis and help clinicians identify individuals in need of greater care. Although the racial background of the study groups was not described by Trivedi and Bruns [1], we presumed that the majority of subjects were Caucasian according to the authors’ well known prior studies. Racial background has been linked to the polymorphisms of genes involved in liver disease, which are associated with disease status, prognosis and response to UDCA therapy [2–4]. Therefore, we examined the association between APRI and progression to hepatic failure in Japanese patients with PBC to evaluate whether APRI could be a clinical indicator of disease outcome across multiple ethnicities.
Journal of Hepatology 2014 vol. 61 j 1438–1452
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Conflict of interest The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] El-Guindi MA, Sira MM, Sira AM, Salem TA, El-Abd OL, Konsowa HA, et al. Design and validation of a diagnostic score for biliary atresia. J Hepatol 2014;61:116–123. [2] Kianifar HR, Tehranian S, Shojaei P, Adinehpoor Z, Sadeghi R, Kakhki VR, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol 2013;43:905–919. [3] Kwatra N, Shalaby-Rana E, Narayanan S, Mohan P, Ghelani S, Majd M. Phenobarbital-enhanced hepatobiliary scintigraphy in the diagnosis of biliary atresia: two decades of experience at a tertiary center. Pediatr Radiol 2013;43:1365–1375.
[4] Liu SX, Huang ZH. The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice. Front Med China 2010;4:342–345. [5] Lin WY, Lin CC, Changlai SP, Shen YY, Wang SJ. Comparison technetium of Tc-99m disofenin cholescintigraphy with ultrasonography in the differentiation of biliary atresia from other forms of neonatal jaundice. Pediatr Surg Int 1997;12:30–33. [6] Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. Hepatology 2009;49:1017–1044.
⇑
Rui Dong Shan Zheng Department of Pediatric Surgery, Children’s Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China ⇑Corresponding author. Address: Department of Pediatric Surgery, Children’s Hospital of Fudan University, and Key Laboratory of Neonatal Disease, Ministry of Health, 399 Wan Yuan Road, Shanghai 201102, China. Tel.: +86 021 64931007; fax: +86 021 64931901. E-mail address: [email protected]
Reply to: ‘‘Scoring system in diagnosing biliary atresia’’ To the Editor: We appreciate the interest of Dong and Zheng in our recent study [1]. Although hepatobiliary scintigraphy (HBS) is one of the most sensitive methods for the diagnosis of biliary atresia (BA), it has a low specificity (70.4%) as reported in a meta-analysis of 81 studies [2]. Sun et al. [3] reported a 13.3% (66/498) false positive rate of HBS. They concluded that the excessive dependence on HBS may contribute to the misdiagnosis of BA. Although HBS, showing biliary excretion, excludes BA, non-excretion neither confirms the diagnosis of BA nor rules out the diagnosis of non-BA aetiologies [4]. Oral phenobarbital can enhance the diagnostic performance of HBS by re-examination one week later [5]; however, for the potential delay in diagnosis it is not routinely practiced [6]. Moreover, the reported BA score specificity (97.67%) [1] cannot be enhanced by HBS, which has a much lower specificity [2]. Liu and Huang [5] reported that if no bile was found in the duodenal tube test (DTT), the drainage tube would be kept for up to 72 h. In some cases, the duodenal fluid changed from white to yellow after several days or weeks. Therefore, persistent examination of the duodenal fluid is very important. This also prolongs the time of diagnosis and is not routinely performed. However, DTT may have a special importance in situations where other tests are not available [6]. An important concept of our BA score [1] is that it depends on parameters that are an integral part of the workup and are routinely performed for patients suffering neonatal cholestasis (NC) whether suspected to be BA or non-BA. Contrarily, HBS and DTT cannot be considered as such. Dong and Zheng were encouraged by the article of Liu and Huang [5] that reports a performance of combined HBS and
DTT of 100% sensitivity and 100% specificity. We read the article with great interest but we found two major concerns. First, recruitment of patients was selective as patients with certain aetiologies were excluded from the study. This selectivity may render the calculated specificity inaccurately a representative one. Furthermore, it supports the concept that these procedures are needed for selected patients. Second, the method of calculating the combined performance is not clear. According to their results, 3 groups of patients can be discriminated: (1) Patients having HBS with no excretion and DTT with no bile; (26 patients with BA). (2) Patients having HBS with excretion and DTT with bile; (41 patients with non-BA). (3) Patients having HBS with no excretion and DTT with bile; (17 patients; 3 were BA and 14 were non-BA). These results can never, in any way, lead to a sensitivity and specificity of 100%. It seems that Liu and Huang [5] simply combined the sensitivity of one test (HBS) with the specificity of the other (DTT) which is unreasonable. Dong and Zheng, suggested that liver biopsy should be avoided whenever possible. We disagree with this concept as we believe that liver biopsy should be performed unless there is a contraindication or when parents refuse the procedure. For that, liver biopsy is considered as an integral part of the diagnostic workup of NC patients and is strongly encouraged according to ‘‘The Cholestasis Guideline Committee’’ of the NASPGN [7]. The aim of liver biopsy in NC is not only to evaluate the features of biliary outflow obstruction but is also an essential tool in revealing the aetiology of the liver disease, and in assessing the fibrosis stage which affects treatment policy. Such targets are irreplaceable by HBS and DTT. For that, liver biopsy is generally considered the ‘‘gold standard’’ compared to other diagnostic
Open access under CC BY-NC-ND license.
1442
Journal of Hepatology 2014 vol. 61 j 1438–1452
JOURNAL OF HEPATOLOGY tools [8]. Recently, Boskovic et al. [9] reported that liver biopsy was superior to DTT in the diagnosis of BA. As for the safety of liver biopsies, Pietrobattista et al. [10] raised the issue asking ‘‘Is juvenile liver biopsy unsafe?’’ They concluded that ultrasound-guided biopsy, performed in a specialized tertiary care paediatric centre by an experienced physician, is considered safe; which is the same in our experience. Although the study population in our study was relatively small, yet, when compared to the studies (discussed in our article) of Chiba and Kasai as well as Gupta et al., evaluating different scores for discriminating BA, our study population was still relatively high [1] (population size was 123, 120 and 135, respectively). Nonetheless, we suggest that the score needs to be validated in different populations with different investigators. The numbers in Fig. 1C and D [1] represent the values of the odds ratio (OR) model. For a parameter like hepatic subcapsular flow, which was found in 29/30 of BA and in 1/30 of the nonBA (Table 3), the OR equals 841. The regression coefficient for the same parameter was 6.735 and the relative risk was 29. This clarifies the higher values in the OR model compared to other models. So, we affirm that there is no mistake.
Conflict of interest The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] El-Guindi MA, Sira MM, Sira AM, Salem TA, El-Abd OL, Konsowa HA, et al. Design and validation of a diagnostic score for biliary atresia. J Hepatol 2014;61:116–123. [2] Kianifar HR, Tehranian S, Shojaei P, Adinehpoor Z, Sadeghi R, Kakhki VR, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatr Radiol 2013;43:905–919.
[3] Sun S, Chen G, Zheng S, Xiao X, Xu M, Yu H, et al. Analysis of clinical parameters that contribute to the misdiagnosis of biliary atresia. J Pediatr Surg 2013;48:1490–1494. [4] Yachha SK. Cholestatic jaundice during infancy. Indian J Gastroenterol 2005;24:47–48. [5] Liu SX, Huang ZH. The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice. Front Med China 2010;4:342–345. [6] Jain AK. Approach to cholestatic Jaundice in newborn. In: Sachdeva A, Dutta AK, Jain MP, Satya PY, Goyal RK, Arora A, et al., editors. Advances in pediatrics. Daryaganj, New Delhi, India: Jaypee brothers Medical publishers (P) Ltd; 2012. p. 126–132. [7] Moyer V, Freese DK, Whitington PF, Olson AD, Brewer F, Colletti RB, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004;39:115–128. [8] Yeh MM. Pathologic diagnosis of biliary atresia on liver biopsy: is tissue the issue? J Gastroenterol Hepatol 2009;24:936–938. [9] Boskovic A, Kitic I, Prokic D, Stankovic I, Grujic B. Predictive value of hepatic ultrasound, liver biopsy, and duodenal tube test in the diagnosis of extrahepatic biliary atresia in Serbian infants. Turk J Gastroenterol 2014;25:170–174. [10] Pietrobattista A, Fruwirth R, Natali G, Monti L, Devito R, Nobili V. Is juvenile liver biopsy unsafe? Putting an end to a common misapprehension. Pediatr Radiol 2009;39:959–961.
Mohamed Abdel-Salam El-Guindi ⇑ Mostafa Mohamed Sira Ahmad Mohamed Sira Tahany Abdel-Hameed Salem Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya, Egypt ⇑Corresponding author. Address: Department of Pediatric Hepatology, National Liver Institute, Menofiya University, 32511 Shebin El-koom, Menofiya, Egypt. Tel.: +20 48 222 2740; fax: +20 48 223 4586. E-mail address: [email protected]
AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis To the Editor: We read with great interest the study by Trivedi, Bruns and colleagues [1] on the association between the AST/platelet ratio index (APRI) and long-term transplant-free survival in patients with primary biliary cirrhosis (PBC). The authors demonstrated that elevated APRI (>0.54) at diagnosis and/or 1 year afterward (APRI-1y) was significantly associated with a future risk of adverse events independently and additively of the ursodeoxycholic acid (UDCA) therapy response, using a deviation cohort from the Elizabeth Hospital, Birmingham (UK), and a validation cohort from the Toronto Center for Liver Diseases (Canada) and the Jena University Hospital (Germany). Since APRI is a simple, widely studied, non-invasive, and easily calculated marker of
liver disease, it represents a useful tool in clinical practice, especially at outpatient clinics, to assess patient prognosis and help clinicians identify individuals in need of greater care. Although the racial background of the study groups was not described by Trivedi and Bruns [1], we presumed that the majority of subjects were Caucasian according to the authors’ well known prior studies. Racial background has been linked to the polymorphisms of genes involved in liver disease, which are associated with disease status, prognosis and response to UDCA therapy [2–4]. Therefore, we examined the association between APRI and progression to hepatic failure in Japanese patients with PBC to evaluate whether APRI could be a clinical indicator of disease outcome across multiple ethnicities.
Journal of Hepatology 2014 vol. 61 j 1438–1452
1443