Hepatic Decompensation Likely Attributable to Simeprevir in Patients with Advanced Cirrhosis

Stine, Jonathan G.; Intagliata, Nicolas M.; Shah, Neeral L.; Argo, Curtis K.; Caldwell, Stephen H.; Lewis, James H.; Northup, Patrick G.

doi:10.1007/s10620-014-3422-x

Cited by 58 publications

(42 citation statements)

References 26 publications

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“…15 In terms of safety and tolerability, a recent case report suggested SMV/SOF may be associated with worsening hepatic decompensation in patients with CP class C cirrhosis. 16 However, in a controlled study, patients with decompensated cirrhosis treated with SMV/SOF had a similar frequency of hepatic decompensation during treatment to matched controls followed for a similar duration of time (9% vs 10%, P 5 .78), 13 suggesting safety events during treatment may reflect the natural history of decompensated cirrhosis. The complexity of establishing a causal relationship between drug exposures and decompensating events in patients with advanced cirrhosis is well recognized.…”

Section: Saxena and Terraultmentioning

confidence: 95%

Current Management of Hepatitis C Virus

Saxena

Terrault

2015

Clinics in Liver Disease

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Chronic hepatitis C virus (HCV) infection currently remains the leading indication for liver transplant in the United States. However, recurrent HCV infection after transplant is universal in those who enter transplant with viremia resulting in reduced posttransplant graft and patient survival rates, caused in large part by progressive recurrent HCV disease. Therefore, successful treatment of HCV in the peri-transplant period, either before or after transplant, is paramount in ensuring improved posttransplant outcomes. This article reviews the experience to date treating HCV in wait-listed patients and liver transplant recipients and the unique challenges encountered when treating this population.

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Section: Saxena and Terraultmentioning

confidence: 95%

Current Management of Hepatitis C Virus

Saxena

Terrault

2015

Clinics in Liver Disease

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“…(Interim) analyses of the prospective phase III study ALLY-1 and compassionate use programs indicate that the use of DCV is safe in patients with advanced cirrhosis [42,44,45]. In contrast, the safety of SMV in patients with decompensated cirrhosis has not been conclusively evaluated [46,47,48,49,50,51]. Recently, a safety warning by the FDA resulted in a contraindication for DSV in combination with OMV and PTV/r in patients with liver cirrhosis CP ≥ B [52].…”

Section: Antiviral Therapy In Hcv-associated Liver Cirrhosis and Hcv mentioning

confidence: 99%

Pre- and Post-Transplant Antiviral Therapy (HBV, HCV)

Welker

Zeuzem

2016

Visc Med

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Background: Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. Methods: A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. Results: Studies investigating IFN-free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. Conclusion: Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently.

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“…Given the hepatic metabolism and risk of hepatotoxicity with the use of paritaprevir in the PrOD regimen [34,36] and simeprevir [42,43], these regimens have not been extensively tested in patients with decompensated disease and are currently not recommended for use in the multi-society guidelines [10••, 11••]. Retrospective data on the off-label use of simeprevir with sofosbuvir in decompensated cirrhotics, largely from the period when these were the only DAA medications available in the USA, revealed response rates ranging from 73-91 % [40,44,45], though reports of cholestatic liver injury with this regimen preclude recommending the use of this regimen in decompensated patients [42,43].…”

Section: Decompensated Cirrhosismentioning

confidence: 99%

“…Retrospective data on the off-label use of simeprevir with sofosbuvir in decompensated cirrhotics, largely from the period when these were the only DAA medications available in the USA, revealed response rates ranging from 73-91 % [40,44,45], though reports of cholestatic liver injury with this regimen preclude recommending the use of this regimen in decompensated patients [42,43].…”

Section: Decompensated Cirrhosismentioning

confidence: 99%

Does SVR Prevent Transplant in HCV?

Jackson

Verna

2016

Curr Hepatology Rep

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Sustained virologic response significantly reduces the risk of cirrhosis, hepatic decompensation, hepatocellular carcinoma, mortality, and the need for liver transplantation in patients with chronic hepatitis C. Thus, broad treatment prior to hepatic decompensation will likely prevent the need for transplant in many individuals. With emerging data on the use of direct acting antiviral regimens in patients with decompensated cirrhosis, it is now also feasible to successfully treat many of these high-risk patients, leading to improvement in liver function as measured by MELD score and Childs-Turcotte-Pugh class in some cases. However, identifying the subgroup of patients who will achieve stabilization or regression of their disease such that experience long-term transplant-free survival remains a clinical challenge. Thus, HCV treatment in the context of decompensated cirrhosis should remain individualized.

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Hepatic Decompensation Likely Attributable to Simeprevir in Patients with Advanced Cirrhosis

Abstract: Protease inhibitors should be used with caution, if at all, in patients with cirrhosis, especially in those with the most advanced disease. We await newer, safer, direct-acting antiviral therapies for such patients, especially those on our transplant list.

Cited by 58 publications

References 26 publications

Current Management of Hepatitis C Virus

Current Management of Hepatitis C Virus

Pre- and Post-Transplant Antiviral Therapy (HBV, HCV)

Does SVR Prevent Transplant in HCV?

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