What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection?

Ioannou, George N.; Feld, Jordan J.

doi:10.1053/j.gastro.2018.10.033

Cited by 161 publications

(168 citation statements)

References 109 publications

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“…Because death due to complications of PH was rare, we would like to highlight the importance of screening programs for the timely diagnosis of HCC in these patients, who otherwise mostly have a favorable prognosis. (5,7) We must acknowledge several limitations of our study. Because of limited sample size, we combined patients with cACLD and decompensated ACLD for the main analyses.…”

Section: Discussionmentioning

confidence: 98%

“…Accordingly, the focus of attention has shifted to the regression of liver disease and risk stratification concepts for personalized followup (FU) of patients who had advanced chronic liver disease (ACLD) before treatment and achieved SVR. (5)(6)(7) Four studies have investigated the impact of viral suppression by SVR to IFN-free treatments on the evolution of PH, (8)(9)(10)(11) as assessed by hepatic venous pressure gradient (HVPG). Although patients with pretreatment subclinical PH (i.e., HVPG 6-9 mm Hg) did not progress to clinically significant portal hypertension (CSPH; HVPG ≥ 10 mm Hg (12)(13)(14) ), less than one fourth of patients who had CSPH before treatment resolved CSPH.…”

Section: Changes In Hepatic Venous Pressure Gradient Predict Hepatic mentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 98%

Section: Changes In Hepatic Venous Pressure Gradient Predict Hepatic mentioning

confidence: 99%

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

et al. 2019

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“…Chronic hepatitis C has become a curable liver disease in the vast majority of patients. Undoubtedly, elimination of HCV by DAA combination therapy is associated with beneficial outcomes, including improvement in fibrosis, reductions in symptoms and extrahepatic manifestations as well as lower risk of liver‐related complications or death . Concomitantly, abnormal liver tests usually normalize after SVR in the vast majority of patients, indicating a biochemical response .…”

Section: Discussionmentioning

confidence: 99%

“…The introduction of direct acting anti‐virals (DAA) as the standard therapy for chronic hepatitis C has fundamentally changed the treatment landscape leading to high viral cure rates in almost all patient populations affected by hepatitis C . Successful HCV eradication, as determined by sustained virological response (SVR) after DAA therapy, reduces patients’ risks for cirrhosis, diminishes extrahepatic manifestations and is associated with fibrosis regression and recovery of liver functionality, prompting the universal recommendation to treat all HCV‐infected patients, regardless of their degree of liver inflammation or fibrosis . However, viral cure from hepatitis C is not synonymous with resolution of liver disease.…”

Section: Introductionmentioning

confidence: 99%

Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C patients treated with DAAs

Tacke

Boeker²,

Klinker

et al. 2019

Liver International

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Background and Aims Liver function tests (alanine aminotransferase, ALT; gamma‐glutamyltransferase, GGT) not always normalize after elimination of hepatitis C virus (HCV) by direct acting antivirals (DAAs), possibly indicating concomitant non‐viral liver diseases. We analysed factors determining the biochemical response (normalized ALT/GGT) of DAA therapy in a large real‐world cohort. Method The German Hepatitis C‐Registry is a national multicenter registry study. Normal ALT was defined ≤35 U/L (female) and ≤50 U/L (male) or, according to AASLD, ≤19 U/L (female) and ≤30 U/L (male), normal GGT ≤40 U/L (female) and ≤60 U/L (male). Results At baseline, ALT was elevated in 3705/4946 (74.9%), ALT (AASLD) in 4669/4946 (94.4%) and GGT in 3018/4906 (61.5%). In this study, 97% of patients achieved SVR12. At week 12 after end of therapy, ALT was elevated in 451/4946 (9.1%), ALT according to AASLD in 1906/4946 (38.5%) and GGT in 863/4879 (17.7%). Persistently elevated ALT after DAA therapy was independently associated with high body mass index (BMI), age <70 years, liver cirrhosis, diabetes, alcohol consumption and not achieving SVR12. Using the stricter AASLD criteria, opioid substitution and male sex were additional predictors. Higher GGT at week 12 was associated with high BMI, age >70 years, liver cirrhosis, diabetes, alcohol consumption, opioid substitution and non‐SVR. Importantly, persistently elevated liver tests after treatment, particularly GGT, were associated with hepatic decompensation and mortality during 4‐years follow‐up. Conclusion Risk factors at baseline (obesity, diabetes, liver cirrhosis, alcohol consumption) are independently associated with persistently elevated liver function tests after SVR, indicating that these patients warrant further hepatological follow‐up. Clinical trial registration: German Clinical Trials Register (DRKS; ID DRKS00009717).

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“…Specifically, patterns of alcohol consumption before and after DAA therapy have not been described, and it is unknown whether patients treated with DAAs who drink alcohol change their use after treatment. Furthermore, although successful DAA therapy has been associated with lower rates of hepatocellular carcinoma (HCC) and mortality, (9,10) and may also influence regression of liver fibrosis, improve portal hypertension, and reduce extrahepatic manifestations of liver disease, (11) a substantial proportion of patients who achieve SVR still develop HCC, cirrhosis, or cirrhosis-related complications. Because alcohol influences these conditions, studies are needed to understand the extent to which alcohol use-both before and after DAA treatment-increases the risk for these adverse outcomes in patients with and without SVR.…”

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confidence: 99%

Alcohol Use and Long‐Term Outcomes Among U.S. Veterans Who Received Direct‐Acting Antivirals for Hepatitis C Treatment

et al. 2020

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Outcomes related to alcohol use after hepatitis C virus (HCV) treatment are unknown in the direct-acting antiviral (DAA) era. We assessed levels of alcohol use before and after HCV treatment and their association with long-term outcomes in a cohort of U.S. veterans. In this retrospective cohort analysis, 29,037 patients who initiated DAA regimens between 2013 and 2015 were followed for a mean of 3.04 years. We categorized alcohol use into three categories (nondrinking, low-level drinking, and unhealthy drinking) using Alcohol Use Disorders Identification Test-Consumption questionnaires administered within 1 year before (baseline) and after treatment. Multivariable Cox proportional hazards regression was used to determine the associations between alcohol use and mortality or liver-related outcomes. Before DAA treatment, 68% of veterans reported nondrinking, 22.9% reported low-level drinking, and 9.1% reported unhealthy drinking. Compared to patients with baseline non-drinking, those with unhealthy drinking had a higher risk of mortality (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.34-1.75) and decompensated cirrhosis (adjusted HR 1.30, 95% CI: 1.06-1.59) and lower likelihood of liver transplantation (adjusted HR 0.24, 95% CI: 0.06-0.92). These associations were greater in patients without sustained virologic response than in those with sustained virologic response. When alcohol use before and after treatment was modeled as a time-varying covariate, similar associations were observed. Survival analysis also found that unhealthy drinking was significantly associated with a lower probability of survival compared with nondrinking. Low-level alcohol use was not associated with increased risk of adverse outcomes. Conclusion: In this large cohort of U.S. veterans with HCV who received DAAs, unhealthy drinking was common and associated with a higher risk of posttreatment mortality. Interventions to achieve alcohol cessation before and during antiviral treatment should be encouraged. (Hepatology Communications 2020;4:314-324).

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What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection?

Cited by 161 publications

References 109 publications

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

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

Baseline risk factors determine lack of biochemical response after SVR in chronic hepatitis C patients treated with DAAs

Alcohol Use and Long‐Term Outcomes Among U.S. Veterans Who Received Direct‐Acting Antivirals for Hepatitis C Treatment

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