Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy

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 as- sessed 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 elastogra- phy (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolu- tion 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 noninva- sive 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 im- proved 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 inter- ventions that lower portal pressure by decreasing intrahepatic resistance

Genome Wide Association Study Identifies Genetic Variants Associated With Early And Sustained Response To (Peg)Interferon In Chronic Hepatitis B Patients: The GIANT-B Study

(Peg)interferon ((Peg)IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR

Genetic variants including PNPLA3-rs738409 C&gt;G, TM6SF2-rs58542926 C&gt;T, MBOAT7-rs641738 C&gt;T, and HSD17B13-rs72613567 T&gt;TA have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the PNPLA3 minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the PNPLA3 G-allele in the overall cohort. Finally, carriage of PNPLA3 G-allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure

Non-invasive risk stratification after HCV-eradication in patients with advanced chronic liver disease

Background & aims: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of non-invasive surrogates of portal hypertension (liver stiffness measurement (LSM) by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio (VITRO)) for development of hepatic decompensation and hepatocellular carcinoma in patients with pre-treatment advanced chronic liver disease (ACLD) who achieved HCV-cure. Approach & results: 276 patients with pre-treatment ACLD and information on pre- and post-treatment (follow-up (FU))-LSM and -VITRO were followed for a median of 36.6 months after the end of interferon-free therapy. FU-LSM (AUROC:0.875(95%CI:0.796-0.954)) and FU-VITRO (AUROC:0.925 (95%CI:0.874-0.977)) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU-LSM25.3kPa and/or FU-VITRO>3.3; 25.0% of patients), the risk of hepatic decompensation at 3-years post-treatment was high (17.4%). Patients within the diagnostic gray-zone for FU-CSPH (17.8% of patients) had a very low-risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n=86) and external (n=162) cohort. Conclusion: FU-LSM/FU-VITRO are strongly and independently predictive of post-treatment hepatic decompensation in HCV-induced ACLD. An algorithm combining these non-invasive markers not only rules-in or rules-out FU-CSPH, but also identifies populations at negligible vs. high-risk for hepatic decompensation. FU-LSM/FU-VITRO are readily accessible and enable risk stratification after SVR, and thus, facilitate personalized management

GastroHep / Management of patients with chronic hepatitis C failing repeated courses of interferonfree direct acting antiviral combination therapy

Background Only few chronic hepatitis C patients treated with interferon (IFN)free direct acting antiviral (DAA) combinations fail to clear the virus. Most patients can be cured by retreatment with another DAA combination; however, some still fail to eradicate the virus. So far, little is known about how to best retreat these patients. In this study we summarise our real world experience of reretreatments. Methods One hundred and two patients who completed a DAAretreatment after virological failure to an IFNfree DAA therapy and reached at least followup 12 were included in this study.Twentyone (20.6%) of them relapsed again after retreatment (mean age 50.0 10.6, 18 male, three female, GT1a:8, GT1b:4, GT1c:1, GT3a:7; GT4:1; cirrhosis:15; resistance associated substitutions [RAS]: 17/19; relapse after:SOF/SMV:2; 3D RBV:4; SOF/DCV RBV:4; SOF/LDV RBV:6; SOF/VEL:3; SOF/VEL/VOX:1; EBV/GZV:1).Treatment duration and addition of RBV were at the discretion of the treating physician. These 21 patients were studied in detail. Results Seventeen of the 21 patients finished a third DAA therapy: 13 achieved SVR12, three relapsed again (cirrhosis:2; SOF/VEL/RBV:GT3a; SOF/LDV/RBV:GT1a; EBV/GZV/SOF/RBV:GT1b), one was lost to followup. One (GT1a, cirrhosis) achieved SVR12 after the third retherapy with 24 weeks of 3D/SOF/RBV, and one (GT3a, cirrhosis) achieved SVR4 after 24 weeks of glecaprevir/pibrentasvir, but died shortly thereafter. Overall, 95 (93.1%) of 102 patients achieved SVR12 after one or more retreatments. Sex, cirrhosis, genotype, RAS or baseline viral load were not associated with retreatment failure. Conclusion Most patients with failure to a DAA therapy achieved SVR after retreatment with a different regimen; however, 13.7% of patients required multiple retreatments.(VLID)511568

Genetic Variation rs16937012 near the NCOA2 Gene Predicts Sustained Response to Interferon in Chronic Hepatitis B patients: the GIANT-B study

WOS: 00036701320000

Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

Background. (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand