INVITED EDITORIALS | 815

2. Runyon BA. Malignancy‐related ascites and ascitic fluid “humoral tests
of malignancy”. J Clin Gastroenterol. 1994;18:94‐98.
3. Runyon BA, Antillon MR. Ascitic fluid pH and lactate: Insensitive and
nonspecific tests in detecting ascitic fluid infection. Hepatology.
1991;13:929‐935.
4. Du L, Zhu S, Lu Z, et al. Ascitic cholesterol is superior to serum‐
ascites albumin gradient in the detection of non‐portal hypertensive
ascites and the diagnosis of mixed ascites. Aliment Pharmacol Ther.
2019;49:91‐98.
5. Gerbes AL, Jüngst D, Xie YN, Permanetter W, Paumgartner G. Ascitic
fluid analysis for the differentiation of malignancy‐related and nonma-
lignant ascites. Proposal of a diagnostic sequence. Cancer.
1991;68:1808‐1814.

DOI: 10.1111/apt.15105

Editorial: ascitic cholesterol – is it superior to serum‐ascites

albumin gradient? Authors’ reply
We thank Dr Patel and Siddiqui for their editorial regarding our causes. SAAG possessed high sensitivity in detecting PH‐related
recent paper.1,2 ascites while ascitic cholesterol has high sensitivity in the detection
We agree with Patel et al that a cut‐off value (45 mg/dL) of of nonPH‐related ascites.
ascitic cholesterol has historically been selected to differentiate To confirm the value of ascitic cholesterol in mixed ascites, net
malignant ascites from benign ascites.3 In our study however, a cut‐ reclassification improvement (NRI) was calculated. The result of NRI
off value of 42 mg/dL was chosen by using the maximal Youden ([Sensitivityascitic cholesterol + specificityascitic cholesterol] – [SensitivitySAAG +
index to achieve the best performance in the differentiation of non‐ specificitySAAG]) is 0.41. In addition, the agreement between peri-
portal hypertensive ascites from portal hypertensive ascites. Ascitic toneal lesions and SAAG/ascites cholesterol was determined using
cholesterol at a cut‐off value of 42 mg/dL had a sensitivity of 88%, kappa (κ) statistics. Peritoneal lesions were defined when thickening,
specificity of 93%, diagnostic accuracy of 91%, NPV of 90%, and adhesion, nodular changes or abnormal metabolism of peritoneum
PPV 92%. These results are comparable to the historic value of based on image results (CT, MRI, PET‐CT). For ascites cholesterol,
45 mg/dL. Since a predescribed cut‐off values (11g/L) for SAAG the kappa value was 0.662; for SAAG, the kappa value was 0.289.
was used in our study, the reviewer suggested a pretermined cut‐ Thus, we conclude ascitic cholesterol is useful in identifying peri-
off value of 45 mg/dL instead of 42 mg/dL for ascitic cholesterol. toneal lesions in mixed ascites.
Then,our manuscript was revised according to the suggestion of
reviewer.
ACKNOWLEDGEMENTS
The hepatic venous pressure gradient (HVPG) measurement is a
reliable method for the assessment of portal hypertension; however, The authors' declarations of personal and financial interests are
the measurement of HVPG requires a dedicated setting and very unchanged from those in the original article.1
experienced operators, hence this expensive method is available only
in specialised centres. In addition, the cost of HVPG measurement is
ORCID
not covered by health insurance in China. Thus, portal hypertension
was defined in our study by clinical manifestations of ascites, Li Du https://orcid.org/0000-0001-8864-6380
portosystemic collateral veins, and splenomegaly. In addition, this Yuhu Song https://orcid.org/0000-0003-1952-654X
criteria for diagnosis of portal hypertension‐related ascites was also
described in previous studies.4–7
LINKED CONTENT
We agree that the majority of enrolled patients had PH and
malignancy. Importantly, 89% (135/152) of malignant ascites, 100% This article is linked to Du et al and Patel and Siddiqui papers. To
(42/42) of tuberculous peritonitis, 100% (2/2) of dialysis‐related view these articles, visit https://doi.org/10.1111/apt.15042 and
ascites, 100% (8/8) of connective tissue disease, 100% (7/7) of eosi- https://doi.org/10.1111/apt.15078.
nophilic gastroenteritis, 100% (1/1) of carcinoma and tuberculosis,
60% (12/20) of pancreatic ascites, and 64% (7/11) of secondary bac-
terial peritonitis had ascitic cholesterol ≥45 mg/dL. These revealed Li Du
high sensitivity for a high ascitic cholesterol in detecting nonPH‐re- Shenghua Zhu
lated benign ascites. SAAG and ascitic cholesterol shared similar Xiaohua Hou
accuracy in the differentiation of PH‐related ascites from other Yuhu Song

© 2019 John Wiley & Sons Ltd


816 | INVITED EDITORIALS
Division of Gastroenterology, Union Hospital, Tongji Medical College
Huazhong, University of Science and Technology, Wuhan, China
Email: yuhusong@yahoo.com
REFERENCES
1. Du L, Zhu S, Lu Z, et al. Ascitic cholesterol is superior to serum‐
ascites albumin gradient in the detection of non‐portal‐hypertensive
ascites and the diagnosis of mixed ascites. Aliment Pharmacol Ther.
2019;49:91‐98.
2. Patel SS, Siddiqui MS. Editorial: ascitic cholesterol ‐ is it superior to
serum‐ascites albumin gradient? Aliment Pharmacol Ther. 2019;49:814‐
815.
3. Gerbes AL, Jungst D, Xie YN, et al. Ascitic fluid analysis for the differ-
entiation of malignancy‐related and nonmalignant ascites. Proposal of
a diagnostic sequence. Cancer. 1991;68:1808‐1814.
DOI: 10.1111/apt.15081
Editorial: infliximab de‐escalation in inflammatory bowel
disease using a therapeutic drug monitoring strategy—early
promise but more data needed
Optimising biologic therapy in patients with inflammatory bowel
disease is important; while these agents are efficacious, rates of
primary nonresponse and secondary loss of response are common,
and our therapeutic armamentarium remains limited. Algorithms
incorporating therapeutic drug monitoring (TDM) with anti‐TNF
therapy have become standard of care. The best evidence is in
the reactive setting at secondary loss of response and has been
endorsed in several consensus guidelines.1–3 The TAXIT trial pro-
vided robust evidence of its benefit in optimising maintenance
therapy for infliximab, providing us with a target therapeutic range
4
of 3‐7 mg/L. To date, there is limited evidence of the role of
TDM to guide dose reduction during maintenance therapy.
In the paper by Lucidarme et al, the authors compared rates
of relapse between a clinical‐based vs a trough level‐based de‐
escalation strategy in patients receiving maintenance infliximab
who were in clinical and biochemical remission at the time of de‐
escalation.5 Patients in the trough level group had a drug level
higher than the therapeutic range of 7 mg/L. The major finding
was that the risk of relapse was lower in the trough‐based strat-
egy rather than clinical‐based strategy (17% vs 37%, P = 0.0078)
The authors demonstrated that the trough level decreased by
approximately half after de‐escalation. This is a simple rule that
can easily be extrapolated to clinical practice. Considering the
trough level‐based cohort, following de‐escalation, the majority of
drug levels remained within the “therapeutic range” of 3‐7 mg/L
(median trough level 3.9 vs 5.95 mg/L in those who relapsed,
© 2019 John Wiley & Sons Ltd
13652036, 2019, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/apt.15105 by Nat Prov Indonesia, Wiley Online Library on [28/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
4. Runyon BA, Montano AA, Akriviadis EA, et al. The serum‐ascites
albumin gradient is superior to the exudate‐transudate concept in
the differential diagnosis of ascites. Ann Intern Med. 1992;117:215‐
220.
5. Khandwalla HE, Fasakin Y, El‐Serag HB. The utility of evaluating low
serum albumin gradient ascites in patients with cirrhosis. Am J Gas-
troenterol. 2009;104:1401‐1405.
6. Farias AQ, Silvestre OM, Garcia‐Tsao G, et al. Serum B‐type natri-
uretic peptide in the initial workup of patients with new onset ascites:
a diagnostic accuracy study. Hepatology. 2014;59:1043‐1051.
7. Wu SS, Lin OS, Chen YY, et al. Ascitic fluid carcinoembryonic antigen
and alkaline phosphatase levels for the differentiation of primary from
secondary bacterial peritonitis with intestinal perforation. J Hepatol.
2001;34:215‐221.
compared to those who did not, respectively). At relapse, trough
levels were available in only 44% of cases.
Inherent to any retrospective study, there are several key limi-
tations. First, the authors defined remission using subjective clinical
endpoints. However, as treatment strategies have evolved, so have
the end points for which we strive. Deep remission is now
regarded as the gold standard. We are also aware that, to achieve
this, our target drug levels need to be higher.6 Second, drug levels
were only available in six patients in the clinical‐based arm; hence
it is possible that a proportion had supra‐therapeutic trough levels
prior to de‐escalation. Furthermore, the current study is cross‐sec-
tional, and therefore provides a “snapshot” of the patients’ disease
course. We are unaware of the disease course prior to de‐escala-
tion. In 32 (22%) cases, de‐escalation was a dose reduction from
10 mg/kg to either 7.5 or 5 mg/kg, suggesting that achieving remis-
sion was initially challenging. Alternatively, if patients were inappro-
priately on a higher initial maintenance dose, it is unsurprising that
they remain in remission when reduced to 5 mg/kg. More informa-
tion is required regarding this cohort to interpreting these findings.
Finally, 146 de‐escalations were performed in 96 patients, hence,
the outcomes from the same patient were considered separately in
the analysis, which may have biased the results.
Moving forward, results from this study provide the framework
for a well‐designed prospective study assessing the risk of relapse
of patients in sustained deep remission prior to being randomised
to either a TDM or clinical‐based strategy. Until we have these