Search

Background: HIV/HCV co-infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT)., Aim: To assess the effects of interferon-free therapy on portal pressure, liver histology and plasma biomarkers in HIV/HCV-coinfected patients with PHT., Methods: Twenty-two patients with paired hepatic venous pressure gradient (HVPG) measurements prior and after successful treatment (SVR) with interferon-free regimens were included. Liver stiffness was assessed by transient elastography and biopsies were scored according to METAVIR. Plasma biomarkers were determined by ELISA., Results: Overall, HVPG decreased from 10.7 ± 4.1 mmHg at baseline to 7.4 ± 4.2 mmHg after HCV treatment (Δ:-3.3 ± 2.7 mmHg; p < 0.001). In patients with clinically significant PHT (HVPG≥10 mmHg, n = 11), HVPG decreased from 14.1 ± 2.9 to 10.4 ± 3.9 mmHg (Δ:-3.7 ± 3.3 mmHg; p = 0.004) and a haemodynamic response (HVPG decrease ≥10%) was observed in 73%. In 64% of patients with subclinical PHT (HVPG 6-9 mmHg, n = 11), portal pressure normalised at SVR. Mean liver stiffness decreased from 20.8 kPa to 11.5 kPa (Δ:-8.8 ± 7.4 kPa; p < 0.001). Fifty percent (7/14) of patients with cirrhosis were re-classified as METAVIR ≤F3 and all patients with decompensated cirrhosis improved their Child-Pugh stage. After successful HCV treatment, 39% still had persistent histological necroinflammatory activity (METAVIR A1), which correlated with less HVPG response and more steatosis. While most biomarkers improved with SVR, METAVIR A1 patients had significantly higher plasma levels of fibrogenic (PDGF, TGF-β) and angiogenic (VEGF, Angiopoietin1) biomarkers., Conclusions: Interferon-free therapy reduces PHT and halts histological necroinflammatory activity in the majority of HIV/HCV-coinfected patients after SVR, which may lead to re-compensation of liver function in cirrhosis. Biomarkers could identify patients with persisting hepatic necroinflammation., (© 2016 John Wiley & Sons Ltd.)

Background: Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells., Aim: To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis., Methods: We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score., Results: In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99., Conclusions: Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention., (© 2012 Blackwell Publishing Ltd.)

Background: The hepatic venous pressure gradient (HVPG) is used as an estimation of portal pressure (PP) in the management of patients with cirrhosis. Two methods are available using either a straight or a balloon catheter, but have never been compared head-to-head., Aim: To compare the two methods of determining HVPG, straight and balloon catheter, regarding reproducibility and reliability., Methods: In 47 patients with liver cirrhosis, HVPG was assessed using both catheters in sequence. In another 29 patients, the wedged hepatic venous pressure (WHVP) determined either with straight or balloon catheter was correlated with a direct measurement of PP. Variation coefficient and intraclass correlation coefficient were calculated., Results: Variation coefficients for balloon catheter were 0.07 (HVPG), 0.02 (WHVP) and 0.06 [free hepatic venous pressure (FHVP)]. Variation coefficients for straight catheter were 0.17 (HVPG), 0.06 (WHVP) and 0.07 (FHVP), demonstrating a significantly wider variation of the HVPG and WHVP measurements (P < 0.001). Comparison of WHVP with PP revealed a correlation coefficient of 0.72 (P = 0.004) using balloon catheter and 0.58 (P = 0.011) using straight catheter., Conclusions: Measurements with the balloon catheter currently represent the most reliable and reproducible method to assess HVPG. The results are of particular clinical relevance if repeated measurements are required for therapeutic adjustments., (© 2010 Blackwell Publishing Ltd.)

Background: Hepatic venous pressure gradient (HVPG) measurement is not a routinely used technique, despite its therapeutic and prognostic value., Aim: To review the role of HVPG from published literature., Methods: Systematic literature review., Results: In acute variceal bleeding, HVPG is prognostic identifying 'difficult to treat' group, which now has defined clinical correlations. In secondary prevention of portal hypertensive bleeding, a reduction to < or = 12 mmHg confers near complete protection against rebleeding. The target of > or = 20% HVPG reduction from baseline needs prospective assessment to test a change of therapy, if no reduction occurs. The acute HVPG response to beta-blockade needs further assessment. In primary prevention, the cost-effectiveness of HVPG measurement is not favourable given the efficacy of medical therapy. In chronic liver disease, wedge hepatic venous pressure (WHVP) is prognostic for survival. Pharmacological reduction in portal pressure decreases complications and improves survival, possibly independent of a concomitant improvement in liver function. This latter requires urgent confirmation as it is clinically very relevant. HVPG monitoring can be used to assess anti-viral therapy particularly in cirrhosis, ergonomically combined with transjugular biopsy., Conclusions: The prognostic and therapeutic value of HVPG is established beyond portal hypertensive bleeding for which there are some clinical surrogates. HVPG measurement should now be part of everyday clinical practice.

Gastro-oesophageal variceal bleeding is the last step in a chain of events that starts with an increased portal pressure, and is followed by the formation and progressive dilatation of gastro-oesophageal varices. When the tension of the thin wall of the varices exceeds its elastic limit, the varices rupture and bleed. Wall tension is directly proportional to variceal pressure (which is a function of portal pressure) and variceal radius, and inversely related to the thickness of the variceal wall. The above facts explain why a high portal pressure (usually determined by the hepatic venous pressure gradient, or HVPG) and the presence at endoscopy of large varices with red wheals, red spots or diffuse redness on the varices (signalling a reduced wall thickness) correlate with the risk of bleeding.

Background: The measurement of the hepatic venous pressure gradient may identify a suboptimal response to beta-blockers in patients with varices at risk for bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide primary prophylaxis has not been examined., Methods: We used decision analysis to evaluate two hepatic venous pressure gradient measurement strategies relative to standard beta-blocker therapy in a hypothetical cohort of patients with high-risk varices: (i) hepatic venous pressure gradient measurement 4 weeks after the initiation of beta-blocker therapy; and (ii) hepatic venous pressure gradient measurement prior to and 4 weeks after the initiation of beta-blocker therapy. The total expected costs, variceal bleeding episodes and deaths were calculated over a 1-year time horizon., Results: Beta-blocker therapy was associated with total costs of $1464, seven variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. One hepatic venous pressure gradient measurement was associated with total costs of $5015, four variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. Two hepatic venous pressure gradient measurements were associated with total costs of $8657, four episodes of variceal bleeding, one variceal bleeding episode-related death and 15 deaths. Compared with beta-blocker therapy alone, the incremental costs per variceal bleeding episode prevented and death averted were, respectively, $108 185 and $355 100 (one hepatic venous pressure gradient measurement) and $202 796 and $719 300 (two hepatic venous pressure gradient measurements). The results were sensitive to the time horizon of the analysis, the probability of bleeding whilst on beta-blockers and the cost of hepatic venous pressure gradient measurement., Conclusion: Hepatic venous pressure gradient measurement to guide primary prophylaxis is an expensive strategy for reducing variceal bleeding or death, especially in patients with limited life expectancy, such as those with advanced, decompensated cirrhosis.