Sebastian Steiner

Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3

To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25‐hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C‐coinfected (HIV/HCV) patients.

Interferon‐free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease

HIV/HCV co‐infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT).

Advances in the management of HIV/HCV coinfection

HCV coinfection has emerged as a major cause of non-AIDS-related morbidity and mortality in HIV-positive patients. As a consequence of the availability of modern combined antiretroviral therapy regimens, for optimally managed HIV/HCV-coinfected patients, the rates of liver fibrosis progression and the risk of liver-related events are increasingly similar to those of HCV-monoinfected patients. Moreover, our understanding of modulators of liver disease progression has greatly improved. In addition to immune status, endocrine, metabolic, genetic and viral factors are closely interrelated and might be important determinants of liver disease progression. In the last decade, a variety of serologic and radiographic tests for noninvasive liver disease staging have been extensively validated and are commonly used in HIV/HCV-coinfected patients. Sustained virologic response prevents end-stage liver disease, hepatocellular carcinoma, and death, with an even greater effect size in HIV-positive compared to HIV-negative patients. As interferon-free regimens achieve comparable rates of sustained virologic response in HIV-negative and HIV-positive patients, HIV/HCV-coinfected patients should from now on be referred to as a special, rather than a difficult-to-treat, population. Our comprehensive review covers all relevant aspects of HIV/HCV coinfection. Beginning with the changing epidemiology, it also provides new insights into the natural history of this condition and gives an overview on non-invasive techniques for the staging of liver disease. Furthermore, it outlines current recommendations for the treatment of acute hepatitis C and summarizes the unprecedented advances in the field of chronic hepatitis C therapy.

Interferon-free treatment with sofosbuvir/daclatasvir achieves sustained virologic response in 100% of HIV/hepatitis C virus-coinfected patients with advanced liver disease.

Aim:We aimed to investigate the safety and efficacy of interferon (IFN) and ribavirin (RBV)-free therapy with sofosbuvir along with daclatasvir (SOF/DCV) in HIV/hepatitis C virus (HCV)-coinfected patients (HIV/HCV), who have an urgent need for effective antiviral therapy. We also assessed its impact on liver stiffness and liver enzymes. Design:Thirty-one patients thoroughly documented HIV/HCV with advanced liver disease (advanced liver fibrosis and/or portal hypertension) who were treated with SOF/DCV were retrospectively studied. Methods:The following treatment durations were applied: HCV-genotype (HCV-GT)1/4 without cirrhosis: 12 weeks; HCV-GT1/4 with cirrhosis: 24 weeks; HCV-GT3: 24 weeks; if HCV-RNA was detectable 4 weeks before the end of treatment, treatment was extended by 4 weeks at a time. Results:Fifty-two percent of patients were treatment-experienced. The majority of patients had HCV-GT1 (68%), whereas HCV-GT3 and HCV-GT4 were observed in 23 and 10% of patients, respectively. Ninety-four percent had liver stiffness greater than 9.5 kPa or METAVIR fibrosis stage higher than F2 and 45% had liver stiffness above 12.5 kPa or METAVIR F4. Portal hypertension (HVPG ≥6 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) were observed in 67% (18/27) and 26% (7/27) of patients, respectively. Sustained virologic response 12 weeks after the end of treatment (SVR12) was achieved in 100% (31/31). Treatment with SOF/DCV was generally well tolerated and there were no treatment discontinuations. HCV eradication improved liver stiffness from 11.8 [interquartile range (IQR): 11.5 kPa] to 6.9 (IQR: 8.2) kPa [median change: –3.6 (IQR:5.2) kPa; P < 0.001] and decreased liver enzymes. The mean time period between treatment initiation and follow-up liver stiffness measurement was 32.7 ± 1.2 weeks. Conclusion:IFN- and RBV-free treatment with SOF/DCV was well tolerated and achieved SVR12 in all HIV/HCV with advanced liver disease. It also significantly improved liver stiffness, suggesting anti-fibrotic and anti-portal hypertensive effects.

Response-guided Boceprevir-based Triple-Therapy in HIV/HCV-coinfected Patients: The HIVCOBOC-RGT Study

BACKGROUND The HIVCOBOC-RGT study (NCT01925183) was the first study to evaluate response-guided shortening of the duration of boceprevir (BOC)-based triple therapy in human immunodeficiency virus (HIV)/hepatitis C virus genotype 1-coinfected patients (HIV/HCV-GT1). METHODS After 4 weeks of pegylated interferon-α-2a/ribavirin (PEGIFN/RBV) lead-in, patients with target-not-detectable HCV-RNA at week 8 (rapid virologic response; LI4W-W8UTND) received 24 weeks of BOC/PEGIFN/RBV (total: 28 weeks [W28]). Patients with target-detectable HCV-RNA at week 8 received 44 weeks of BOC/PEGIFN/RBV (total: 48 weeks [W48]). RESULTS Fourteen patients (67%) had LI4W-W8UTND and were eligible for the shortened W28 arm, while 7 (33%) patients were allocated to the W48 arm. No breakthrough or relapse occurred in the W28 arm, resulting in a sustained virologic response (SVR12TND) rate of 100% (12/12). In the W48 arm, the SVR12TND was 50% (3/6), with 3 patients meeting the futility rule at treatment week 12. The preliminary overall SVR12TND rate was 83% (15/18). Serious adverse events were observed in 5 (24%) patients, with 2 (10%) patients requiring surgical treatment of abscesses. CONCLUSIONS The majority of HIV/HCV-GT1 were eligible for response-guided shortening of treatment duration to W28 and all of these patients had a SVR12TND. If second-generation direct-acting antivirals are not available, W28 of BOC-based triple therapy may be recommended.

Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study

AbstractHealth-related quality of life (HRQoL) is impaired in HIV/HCV-coinfected patients (HIV/HCV) and further decreased by interferon (IFN)-based therapies. We aimed to investigate the impact of IFN- and ribavirin (RBV)-free therapies on HRQoL and fatigue.Thirty-three HIV/HCV-coinfected patients who underwent HCV therapy with sofosbuvir in combination with daclatasvir or ledipasvir were retrospectively studied and compared to 17 patients who received boceprevir (BOC)/PEGIFN/RBV. HRQoL (mental [MCS] and physical [PCS] component score) and fatigue were assessed using the SF-36 (Short Form 36 Health Survey) and the FSS (Fatigue Severity Scale), respectively. HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU).At BL, both domains of HRQoL as well as the severity of fatigue were significantly impaired in HIV/HCV, when compared to a healthy population. Already during treatment, IFN/RBV-free therapy improved physical health (PCS: 41.4 ± 9.7 vs. 47.0 ± 11.2; P < 0.01) and reduced fatigue (37.8 ± 14.0 vs. 31.9 ± 15.2; P = 0.01), whereas we observed a substantial worsening of both factors in patients treated with BOC/PEGIFN/RBV. Since these improvements were maintained, patients treated with IFN/RBV-free therapy reported an improvement in physical health (PCS: 41.4 ± 9.7 vs. 45.8 ± 12.7; P < 0.01) and fatigue (37.8 ± 14.0 vs. 30.9 ± 14.8; P = 0.04) at FU. While AIDS-patients had a higher severity of fatigue at BL and showed a reduction of fatigue (42.5 ± 14.0 vs. 31.6 ± 15.7; P = 0.01), mental health only improved in patients without AIDS (MCS: 35.7 ± 5.3 vs.40.7 ± 6.4; P = 0.04). HIV/HCV with severe fatigue at BL (>median BL-FSS) showed most pronounced improvements in severity of fatigue (49.7 ± 7.0 vs. 32.0 ± 16.7; P < 0.01).In contrast to IFN-based regimens, highly effective and well-tolerated IFN-/RBV-free regimens improve HRQoL (especially physical health) and fatigue already during treatment. All patients with HIV/HCV coinfection should be considered for HCV treatment; however, patients with severe fatigue should be prioritized.

Treatment intensification with boceprevir in HIV-positive patients with acute HCV-genotype 1 infection at high risk for treatment failure.

SummaryBackgroundAccording to current guidelines, the universal use of direct-acting antiviral agents in HIV-positive patients with acute hepatitis C (AHC) is not recommended. We aimed to evaluate the concept of treatment intensification with boceprevir (BOC) in HIV-positive patients with HCV-genotype 1 AHC (HIV/AHC-GT1) at high risk for failure to pegylated interferon/ribavirin therapy (PEGIFN/RBV).MethodsNineteen consecutive HIV-positive patients with HIV/AHC-GT1 who underwent antiviral therapy were studied retrospectively.Patients were treated with PEGIFN/RBV for 24 or 48 weeks, depending on rapid virologic response (RVR; undetectable HCV-RNA at treatment week [W] 4). Patients without complete early virologic response (cEVR; undetectable HCV-RNA at W 12) were offered treatment intensification with BOC at W 12, resulting in 36 weeks of BOC/PEGIFN/RBV triple therapy (total treatment duration: 48 weeks).ResultsThirty-seven percent (7/19) of patients had an RVR and 74 % (14/19) of patients had a cEVR. BOC was used in four out of five patients who did not achieve cEVR and one patient elected to proceed with PEGIFN/RBV.Sustained virologic response (SVR; undetectable HCV-RNA 24 weeks after the end of treatment) rates were 100 % (14/14) among patients with cEVR treated with PEGIFN/RBV and 75 % (3/4) among patients without cEVR receiving BOC add-on. The patient without cEVR who preferred to continue with PEGIFN/RBV did not achieve SVR. Thus, the overall SVR rate was 89 % (17/19) in intention to treat analysis.ConclusionsBOC add-on in selected HIV/AHC-GT1 resulted in a high overall SVR rate. If 2nd generation direct-acting antiviral agents (DAAs) are not available, treatment intensification with BOC can be considered in HIV/AHC-GT1 at high risk for failure to PEGIFN/RBV.