This study confirms the prognostic value of PPG on patient outcomes, including rebleeding and OHE, the study revealed the necessity of tailoring PPG thresholds according to liver function, and identifies the optimal PPG thresholds in patients with different Child–Pugh grades. The advantages of the current study are as follows: 1) being conducted on the largest real-world TIPS cohort to date; 2) updating TIPS threshold in the era of covered stents with lower shunt dysfunction rate and possibly more stable post-procedure PPG variation; 3) applying multiple statistical methods including PSM and competing risk to validate the robustness of our findings; and 4) all the patients enrolled in this study underwent TIPS for secondary prophylaxis of rebleeding under local anesthesia, which avoids the influence of emergency vasoconstrictive drugs and sedation on PPG measurement. Therefore, immediate PPG can represent the real situation of PV pressure in this study.
A target threshold of 12 mmHg was proposed and implemented over 30 years ago4, 5, 8, 9, 13, 20–23, and has since been recommended by Baveno VII1, derived from uncoated TIPS. However, this has not yet been confirmed for covered TIPS. Therefore, it is important to explore the PPG threshold suitable for covered-stent TIPS. Moreover, the optimal PPG threshold should be tailored according to Child–Pugh classes because patients with different liver function classes have different PPG reduction tolerances.
Bosch et al. hypothesized that higher PPGs, such as 14 mmHg, might be more appropriate for covered stents than lower PPGs since their well-maintained patency would reduce the need to immediately lower post-TIPS PPG, which is required to counter gradually reduced shunt diameter and increased PPG with bare stents.13 A recent cohort study of 216 patients confirmed this hypothesis, the study found that post-procedure PPGs higher than 12 mmHg did not necessarily indicate higher variceal rebleeding rates after 12 months24. Therefore, we explored this issue using a larger TIPS cohort.
In this study, patients with PPGs > 12 mmHg after TIPS had a higher incidence of rebleeding than those with PPGs < 12 mmHg. However, this result was not robust after PSM. PPGs > 14 mmHg also had a higher incidence of rebleeding than PPGs < 14 mmHg, but provided a net benefit higher than that of > 12 mmHg. However, this result was not robust after PSM. Nevertheless, when the entire cohort was stratified according to Child–Pugh class, an indicator of liver function, we found that 12 mmHg did not affect rebleeding or OHE rates in Child–Pugh class A patients. However, 12 mmHg affected rebleeding in Child–Pugh class B and C patients. These results indicate that a one-size-fits-all strategy may not be suitable for setting a PPG threshold, with liver function being important in tailoring PPG targets for different patients25, 26. Therefore, we explored several PPG thresholds to propose an appropriate threshold for each Child–Pugh class.
Neither 10 nor 14 mmHg PPG affected rebleeding or OHE after TIPS in Child–Pugh class A patients, perhaps reflecting their relatively low cumulative incidence, increasing the difficulty in identifying significant differences. However, the results showed that patients had numerically lower rebleeding rates with PPGs < 10 mmHg than those with PPGs > 10 mmHg, which was not observed at PPG thresholds of 12 and 14 mmHg, indicating that 10 mmHg might be a more appropriate threshold than 12 and 14 mmHg. Attia et al. reported that patients with lower Child–Pugh scores could tolerate lower PPGs than those with higher Child–Pugh scores 26. Therefore, we hypothesized that a PPG threshold of < 10 mmHg might be suitable for patients with Child–Pugh class A. Unfortunately, the small number of patients with PPG values in our cohort did not allow powered statistical tests.
A PPG threshold of 12 mmHg, but not 14 mmHg, affected rebleeding and OHE rates in Child–Pugh class B patients, indicating that a PPG threshold of 12 mmHg remains appropriate for them. In contrast, a PPG threshold of 14 mmHg appeared to be effective in reducing the rebleeding risk in Child–Pugh class C patients. These patients had a high incidence of OHE (> 50%), which we believe causes the lack of a significant OHE effect. Furthermore, a lower PPG threshold generally indicates more shunting, which might further reduce liver perfusion and exacerbate liver damage based on severely impaired function6, 27–29. Therefore, we hypothesized that a PPG of < 14 mmHg is better than a PPG of < 12 mmHg for Child–Pugh class C patients.
Although the percentage of pressure reduction is an important rebleeding indicator, several studies have explored its effective range5–9, 30. In this study, post-TIPS PPGs remained high in patients with high pre-TIPS PPGs (1065 had pre-TIPS PPGs ≥ 24 mmHg), even when the reduction exceeded a certain percentage (e.g., a 50% reduction of 40 mmHg was 20 mmHg). Consequently, these patients were still exposed to adverse outcomes, and meaningful results could not be obtained.
Our study has several limitations. First, it was a retrospective study with incomplete information on post-TIPS liver function and the causes of rebleeding or death. However, we included consecutive patients to avoid excessive bias. Second, to date, the PPG threshold of < 12 mmHg has been the goal of TIPS. Therefore, only approximately 16% of patients in this study had post-TIPS PPG ≥ 12 mmHg, increasing the difficulty of identifying significant differences in PSM analyses when the sample size was further reduced.
In conclusion, a PPG threshold < 12 mmHg after TIPS may not be optimal for every patient. Different PPG thresholds may be required in patients with different liver function categories. Moreover, although a PPG threshold of < 12 mmHg may be suitable for Child–Pugh class B patients, a PPG threshold of < 14 mmHg is more suitable for Child–Pugh class C patients. Given the retrospective nature of this study, these results should be confirmed in future prospective studies with larger cohorts.