Q2. What is the role of NF-jB in the liver?
NF-jB plays a central role in the inflammation-fibrosis-cancer axis in the liver by inducing tumor necrosis factor alpha and interleukin-6 activating hepatic stellate cells to produce profibrogenic factors.
Q3. What is the effect of NSAIDs on the liver?
The NSAIDs used in this model inhibited oxidative stress, COX-2 activity and nuclear factor kappa B (NF-jB) translocation to the nucleus.
Q4. How long after diagnosis did PSC-IBD patients develop CRC?
Seven (7/722) IBD control patients developed CRC (SIR, 1.2; 95% CI: 0.3-3.0) after a median time span of 4 years (range, 0-19) after diagnosis (4 UC, 1 CD, and 1 IBD unspecified).
Q5. What factors may have resulted in an earlier detection of the disease?
Introduction of MRC as a noninvasive diagnostic tool, physician awareness, and an increase in routine laboratory blood tests may have resulted in an earlier detection of the disease over time.
Q6. What was the definition of colonoscopic surveillance?
Colonoscopic surveillance was defined as a full colonoscopy at PSC diagnosis and every 1-2 years after diagnosis in PSC-IBD patients.
Q7. What was the common cause of death for patients with PSC?
Five (12%) patients were diagnosed with PSC and CCA at initial presentation, another 6 (15%) within the first year, 15 (37%) between 1 and 10 years, and the remaining 15 (37%) developed a CCA 10 or more years after PSC diagnosis.
Q8. How many cases were in the population-based cohort?
The second PSC cohort, accrued from the three Dutch transplantation centers outside the study region, yielded 450 cases, of whom 134 (30%) were also present in the population-based cohort.
Q9. How long does the study take to start surveillance?
CRC develops, on average, morethan 20 years earlier, compared to IBD patients and the general population, and ranks among the top four causes of death in PSC patients, corroborating current guidelines to start surveillance every 1-2 years from start of diagnosis.
Q10. How many times per month did NSAIDs reduce the risk of death?
a large, prospective study showed that NSAIDs reduced the risk of death resulting from chronic liver disease, even in individuals who only used NSAIDs less than two to three times per month.33
Q11. What is the effect of acetyl salicylic acid on liver fibros?
There are some reports that COX-2 is overexpressed in liver cirrhosis from hepatitis B virus and hepatitis C virus, as well as in various malignancies, including HCC.29,30 Interestingly, Ch avez et al.31 showed a beneficial effect of acetyl salicylic acid and ibuprofen in an experimental rat model of liver fibrosis.
Q12. What factors play an important role in survival analysis?
When comparing studies on the natural history of PSC, several factors play an important role in survival analysis: starting point of disease; definition of endpoints; and proportion of patients that underwent LT.
Q13. How long did the median survival of PSC patients last?
Estimated median survival times from diagnosis until the combined endpoint LT (n 5 94) or PSC-related death (n 5 73), until LT, or until PSC-related death were 21.2, 27.0, and 33.6 years, respectively.
Q14. What is the way to correct for the lack of data?
The capture-recapture method, which can correct for this, could not be applied because three of four data sources were local databases.
Q15. What was the risk of CCA after 10 years?
Cumulative risk of high-grade dysplasia or CRC after 10, 20, and 30 years since PSC diagnosis was 3%, 7%, and 13%, respectively (Fig. 4A).
Q16. What was the risk of CRC in PSC-IBD patients?
When combining PSC-CRC patients from the population-based and transplantation centers cohorts, 50% (9 of 18) of the nonsurveilled patients and 16% (3 of 19) who received regular surveillance colonoscopies died of CRC (P 5 0.038; Fig. 4C).