Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality

Jansen, Christian; Möller, Philipp T.; Meyer, Carsten H.; Kolbe, Carl Christian; Bogs, Christopher; Pohlmann, Alessandra; Schierwagen, Robert; Praktiknjo, Michael; Abdullah, Zeinab; Lehmann, Jennifer; Thomas, Daniel; Strassburg, Christian P.; Latz, Eicke; Mueller, Sebastian; Rössle, Martin; Trebicka, Jonel

doi:10.1002/hep.29612

Cited by 74 publications

(64 citation statements)

References 54 publications

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“…In line with this concept, CRP levels as well as white blood cell counts were elevated in the patients with ACLF at surgery as compared with patients who developed ACLF later on after surgery. Notably, however, survival was similar in both groups of patients, which probably reflects the fact that the severity of ACLF after surgery or, alternatively, the systemic inflammatory response, was already highly elevated but was not apparent by routine markers, such as CRP and WBC, as recently demonstrated in patients receiving TIPS …”

Section: Discussionmentioning

confidence: 57%

The Development and Outcome of Acute‐on‐Chronic Liver Failure After Surgical Interventions

Klein¹,

Chang²,

et al. 2019

Liver Transpl

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Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality. Precipitating events, including hemorrhage and infections, contribute to ACLF development, but the role of surgery remains unknown. We investigated the development of ACLF in patients with cirrhosis undergoing surgery. In total, 369 patients with cirrhosis were included in the study. The clinical and laboratory data were collected prior to and on days 1-2, 3-8, and 9-28, and at 3 and 12 months after surgery. Surgery type was classified as limited or extensive, as well as liver and nonliver surgery. A total of 39 patients had baseline ACLF. Surgery was performed during acute decompensation in 35% of the rest of the 330 patients, and 81 (24.5%) developed ACLF within 28 days after surgery. Surrogate markers of systemic inflammation were similar in patients who developed ACLF or not. Age, sex, serum sodium, baseline bacterial infection, and abdominal nonliver surgery were independent predictors for the development of ACLF after surgery. Patients who developed ACLF within 28 days after surgery had a higher mortality at 3, 6, and 12 months. Survival did not differ between patients with ACLF at surgery and those developing ACLF after surgery. Development of ACLF within 28 days after surgery and elevated alkaline phosphatase and international normalized ratio were independent predictors of 90-day mortality. Independent predictors of 1-year all-cause mortality were alkaline phosphatase, Model for End-Stage Liver Disease score, and preoperative hepatic encephalopathy, whereas nonliver surgery was associated with improved survival. ACLF frequently develops in patients with cirrhosis undergoing surgery, especially in those with active bacterial infection, lower serum sodium, and kidney or coagulation dysfunction. Prognoses of ACLF both at and after surgery are similarly poor. Patients with cirrhosis should be carefully managed perioperatively.Liver Transplantation 26 227-237 2020 AASLD.

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Section: Discussionmentioning

confidence: 57%

The Development and Outcome of Acute‐on‐Chronic Liver Failure After Surgical Interventions

Klein¹,

Chang²,

et al. 2019

Liver Transpl

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“…However, C-reactive protein and white blood cell count may not be suitable early markers of systemic inflammation. In a recent study, patients in which levels of inflammatory markers were higher in the hepatic vein than in the portal vein developed more organ failure and showed a worse outcome [45]. Therefore, while systemic inflammation might be induced by PHT, it persists in some patients even when PHT has been effectively treated and may lead to ACLF.…”

Section: Bacterial Translocation and Systemic Inflammationmentioning

confidence: 99%

“…Especially, when PHT is present (increased pressure in the portal vein and the mesenteric veins collecting blood from the splanchnic organs to the liver), complications arise [42]. A TIPS is the most effective treatment of PHT and yet, even after this procedure, many patients develop complications of liver disease [43,44], especially due to the spillover of inflammation with resulting development of ACLF as shown by recent data [5,45,46]. Additionally, it was found that the presence of ascites, as a sign of decompensation, determines the composition of the circulating microbiome in the portal vein compared to the hepatic vein, right atrium, and peripheral venous blood, and that specific circulating microbiome members correlate with inflammatory markers [47].…”

Section: Bacterial Translocation and Systemic Inflammationmentioning

confidence: 99%

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

2018

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Acute-on-chronic liver failure (ACLF) is considered a distinct syndrome in patients with liver disease, with systemic inflammation playing a central role. Portal hypertension (PHT) is also aggravated by inflammation and may subsequently impact the course of ACLF. PHT is more than just an increase in portal pressure in the portal venous system; it aggravates the course of liver disease and, thus, also facilitates the development of acute decompensation and ACLF. A critical mechanistic link between PHT and ACLF might be the gut-liver axis, which is discussed in this review.

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“…Systemic inflammation is known to be the key mediator for the development of acute-on-chronic liver failure (ACLF), and an increase in leucocytes and Creactive protein is strongly associated with the onset of ACLF (6). Nevertheless, activation of Kupffer cells and hepatic monocyte recruitment in ACLF suggest an important role of hepatic inflammation in ACLF development (7,8). Mechanistically, bacterial translocation takes place in advanced liver disease with portal hypertension, resulting in consecutive inflammation and oxidative stress in the portal venous compartment (9,10).…”

Section: Introductionmentioning

confidence: 99%

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

et al. 2020

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Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl 4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl 4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).Queck et al. MCP-1 in Decompensated CirrhosisConclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.

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Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality

Abstract: This study demonstrates that the presence of systemic inflammation predisposes patients to develop increased liver stiffness after TIPS, a predictor of organ failure and death. (NCT03072615) (Hepatology 2018;67:1472-1484).

Cited by 74 publications

References 54 publications

The Development and Outcome of Acute‐on‐Chronic Liver Failure After Surgical Interventions

The Development and Outcome of Acute‐on‐Chronic Liver Failure After Surgical Interventions

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis

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