No abstract

Background and Aims Sustained virologic response (SVR) to interferon (IFN)‐free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN‐free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH. Approach and Results The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow‐up [FU]) IFN‐free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08‐1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC],  < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86‐0.92) in most patients, especially if assessed in a sequential manner. Conclusions Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An “immediate” HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.

Summary 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.

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Associates as well as travel support from Boehringer Ingelheim and Gilead.