Review for 10.1186/s12876-021-01704-w (2021)

Reviewer’s report
Title: 
A Systematic Review on Pharmacokinetics, Cardiovascular Outcomes and
Safety Profiles of Statins in Cirrhosis
Version: 
1 
Date: 
22 Feb 2021
Reviewer's report:
Dear Authors,
Thank you for re-submitting your work entitled, "A Systematic Review on
Pharmacokinetics, Cardiovascular Outcomes and Safety Profiles of Statins in
Cirrhosis." Most of my concerns have been well addressed by your revisions,
including changes to the formatting of tables and clarifications on statin
metabolism.
There is one revision that may require further clarification. With regards to the
statement, "Until new data is available, decompensated cirrhosis may still be
considered as a contraindication for statins." The referenced guidelines here are
from 2006, since which time we have a variety of prospective and retrospective
data that note potential benefit of statins in decompensated cirrhosis. There is
data, some of which you have referenced here, which does note lower risks in
patients with decompensated Childs Pugh B cirrhosis as compared to Childs
Pugh C cirrhosis. 
At our institution, the existing statin prescriptions are being
continued for patients with decompensated cirrhosis - with close monitoring.
Updated literature stating that statin use may be a contraindication could
interfere with the ability of for trained Hepatologists to prescribe statins in a
carefully monitored environment.
Finally, I recommend minor grammatical changes as below:
"Solute carrier (SLC) membrane transporters, such as organic anion transporting
polypeptide (OATP) 1B1, are found in the liver and are responsible for the
transport of multiple statins from the portal vein into the hepatocytes."
""The authors suggested that the changes in the hepatic OATP expression
associated with hepatic impairment that altered the liver uptake of rosuvastatin
which resulted in lower first pass effect and higher systemic bioavailability.
Indeed, the expression of multiple SLC and ABC transporters are altered by the
presence of cirrhosis."
""The lower rate of first-pass metabolism and minimal CYP450 metabolism of
pitavastatin could potentially explain the only minor, non-significant increase of
AUC and CMax in Child-Pugh A" 
With minor revisions to the above sections, I expect this will be an excellent
addition to the literature on the exciting topic of statin use in cirrhosis.
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