Title: Soluble CD163 is a predictor of fibrosis and hepatocellular carcinoma development in
nonalcoholic steatohepatitis
Version: 1 Date: 11 Oct 2022
Reviewer's report:
In this study, the authors firstly demonstrated the increased serum sCD163 levels were strongly
associated with the progression of fibrosis, inflammation grade, and hepatocyte ballooning. The
serum sCD163 levels alterations from the first-time to second-time liver biopsies have increased
in inflammation and fibrosis progressed patients compared to fibrosis and inflammation
improved patients. Lastly, the sCD163 levels indicated could serve as a serum marker for NASH
prognosis and liver carcinogenesis.
The novel prognostic markers for HCC patients with NAFLD backgrounds are of paramount
importance. The wide differences in sCD163 levels between the first-time and second-time liver
biopsies only detected in inflammation and fibrosis progressed patients are interesting, and it
has the potential of being a non-invasive marker to evaluate the liver tissue changes. However,
I still have some issues for the authors to improve:
1. Fig. 2: The diagnosability of sCD163 should be compared with the other existing serum
markers by the AUC, sensitivity, specificity, PPV, and NPV, and listed in a table. Besides,
whether the combination of sCD163 and the other existing serum markers could improve
diagnosability should be studied further.
2. Fig. 3: The information about the therapy methods of those 119 patients with NAFLD who
underwent repeated biopsies should be mentioned.
3. Fig. 4: The levels of sCD163 of HCC patients, who have no NAFLD background, should be
compared together in Fig. 4a.
4. The multivariate analysis should be performed to investigate whether the sCD163 levels
could serve as an independent marker for NAFLD diagnosis, NASH prognosis, and liver
carcinogenesis.
5. CD68 is a marker of macrophages, and CD163 could distinguish M2 macrophages from M1
macrophages, so the relationships between M2 macrophages and NASH/NAFLD progression
should be discussed further.
6. It is inconsistent that the description in Results, line 130: “119 patients with NAFLD who
underwent repeated biopsies” and the description in Discussion, line 180: “287 patients with
NAFLD who underwent repeated liver biopsies”.
7. The names of horizontal and vertical coordinates should be presented in Figures.
8. Figure S2, line 12: “b. sCD168” ?
Title: Soluble CD163 is a predictor of fibrosis and hepatocellular carcinoma development in
nonalcoholic steatohepatitis
Version: 1 Date: 11 Oct 2022
Reviewer's report:
In this study, the authors firstly demonstrated the increased serum sCD163 levels were strongly
associated with the progression of fibrosis, inflammation grade, and hepatocyte ballooning. The
serum sCD163 levels alterations from the first-time to second-time liver biopsies have increased
in inflammation and fibrosis progressed patients compared to fibrosis and inflammation
improved patients. Lastly, the sCD163 levels indicated could serve as a serum marker for NASH
prognosis and liver carcinogenesis.
The novel prognostic markers for HCC patients with NAFLD backgrounds are of paramount
importance. The wide differences in sCD163 levels between the first-time and second-time liver
biopsies only detected in inflammation and fibrosis progressed patients are interesting, and it
has the potential of being a non-invasive marker to evaluate the liver tissue changes. However,
I still have some issues for the authors to improve:
1. Fig. 2: The diagnosability of sCD163 should be compared with the other existing serum
markers by the AUC, sensitivity, specificity, PPV, and NPV, and listed in a table. Besides,
whether the combination of sCD163 and the other existing serum markers could improve
diagnosability should be studied further.
2. Fig. 3: The information about the therapy methods of those 119 patients with NAFLD who
underwent repeated biopsies should be mentioned.
3. Fig. 4: The levels of sCD163 of HCC patients, who have no NAFLD background, should be
compared together in Fig. 4a.
4. The multivariate analysis should be performed to investigate whether the sCD163 levels
could serve as an independent marker for NAFLD diagnosis, NASH prognosis, and liver
carcinogenesis.
5. CD68 is a marker of macrophages, and CD163 could distinguish M2 macrophages from M1
macrophages, so the relationships between M2 macrophages and NASH/NAFLD progression
should be discussed further.
6. It is inconsistent that the description in Results, line 130: “119 patients with NAFLD who
underwent repeated biopsies” and the description in Discussion, line 180: “287 patients with
NAFLD who underwent repeated liver biopsies”.
7. The names of horizontal and vertical coordinates should be presented in Figures.
8. Figure S2, line 12: “b. sCD168” ?
Please review this paper.
user
Title: Soluble CD163 is a predictor of fibrosis and hepatocellular carcinoma development in
nonalcoholic steatohepatitis
Version: 1 Date: 11 Oct 2022
Reviewer's report:
In this study, the authors firstly demonstrated the increased serum sCD163 levels were strongly
associated with the progression of fibrosis, inflammation grade, and hepatocyte ballooning. The
serum sCD163 levels alterations from the first-time to second-time liver biopsies have increased
in inflammation and fibrosis progressed patients compared to fibrosis and inflammation
improved patients. Lastly, the sCD163 levels indicated could serve as a serum marker for NASH
prognosis and liver carcinogenesis.
The novel prognostic markers for HCC patients with NAFLD backgrounds are of paramount
importance. The wide differences in sCD163 levels between the first-time and second-time liver
biopsies only detected in inflammation and fibrosis progressed patients are interesting, and it
has the potential of being a non-invasive marker to evaluate the liver tissue changes. However,
I still have some issues for the authors to improve:
1. Fig. 2: The diagnosability of sCD163 should be compared with the other existing serum
markers by the AUC, sensitivity, specificity, PPV, and NPV, and listed in a table. Besides,
whether the combination of sCD163 and the other existing serum markers could improve
diagnosability should be studied further.
2. Fig. 3: The information about the therapy methods of those 119 patients with NAFLD who
underwent repeated biopsies should be mentioned.
3. Fig. 4: The levels of sCD163 of HCC patients, who have no NAFLD background, should be
compared together in Fig. 4a.
4. The multivariate analysis should be performed to investigate whether the sCD163 levels
could serve as an independent marker for NAFLD diagnosis, NASH prognosis, and liver
carcinogenesis.
5. CD68 is a marker of macrophages, and CD163 could distinguish M2 macrophages from M1
macrophages, so the relationships between M2 macrophages and NASH/NAFLD progression
should be discussed further.
6. It is inconsistent that the description in Results, line 130: “119 patients with NAFLD who
underwent repeated biopsies” and the description in Discussion, line 180: “287 patients with
NAFLD who underwent repeated liver biopsies”.
7. The names of horizontal and vertical coordinates should be presented in Figures.
8. Figure S2, line 12: “b. sCD168” ?
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