Systematic review: current concepts and challenges for the direct‐acting antiviral era in hepatitis C cirrhosis

Majumdar, Avik; Kitson, Matthew T.; Roberts, Stuart K.

doi:10.1111/apt.13633

Cited by 135 publications

(142 citation statements)

References 111 publications

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“…DAA-based regimens are currently recommended by international guidelines as the standard of care for compensated cirrhotic patients because of their virological efficacy, ease of use, and tolerability [54].…”

Section: Hcv-related Compensated Cirrhosismentioning

confidence: 99%

“…In treatment-experienced patients with HCV-1 cirrhosis, the addition of ribavirin to sofosbuvir/ledipasvir allows for shortening treatment to 12 vs. 24 weeks of treatment without ribavirin, without compromising SVR [19,[54][55][56][57][58][59][60].…”

Section: Sofosbuvir/ledipasvirmentioning

confidence: 99%

“…The US FDA has issued a warning that treatment with ritonavir-boosted paritaprevir, dasabuvir, and ombitasvir can cause serious liver injury in patients with more advanced liver disease [19,54,[61][62][63][64][65]. Moreover, these combinations are no longer recommended by the AASLD or EASL [36,66].…”

Section: Paritaprevir/ritonavir Ombitasvir and Dasabuvir With/ Withmentioning

confidence: 99%

“…Treatment-naïve and treatment-experienced patients infected with subtype 1b as well as treatment-naive patients infected by genotype 4 should receive this combination for 12 weeks without ribavirin; treatment should be prolonged to 16 weeks with the addition of ribavirin in genotype 1a patients with higher viral load (≥ 800,000 IU/mL) or with baseline NS5A RASs conferring resistance to elbasvir, as well as in genotype 4 treatment-experienced patients with higher viral load (≥ 800,000 IU/mL) [14,19,54,[68][69][70][71][72]. C-SALVAGE examined the use of elbasvir/grazoprevir plus R ribavirin BV in patient with chronic HCV genotype 1 infection (cirrhotic and non-cirrhotic patients) after failure of peg-IFN and ribavirin [69].…”

Section: Elbasvir/grazoprevirmentioning

confidence: 99%

“…Nonetheless, in settings where another option is not available, this combination (or even the combination peg-IFN plus ribavirin) remains acceptable based on several studies [19,54,[74][75][76][77].…”

Section: Sofosbuvir/ribavirinmentioning

confidence: 99%

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Current and future challenges in HCV: insights from an Italian experts panel

et al. 2017

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Section: Hcv-related Compensated Cirrhosismentioning

confidence: 99%

Section: Sofosbuvir/ledipasvirmentioning

confidence: 99%

Section: Paritaprevir/ritonavir Ombitasvir and Dasabuvir With/ Withmentioning

confidence: 99%

Section: Elbasvir/grazoprevirmentioning

confidence: 99%

Section: Sofosbuvir/ribavirinmentioning

confidence: 99%

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Current and future challenges in HCV: insights from an Italian experts panel

et al. 2017

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Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harborsTP53inactivation

et al. 2022

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Introduction The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct‐acting antivirals (DAA) or interferon (IFN) are still not fully understood. Methods Sixty‐nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole‐exome sequencing. Results Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV‐positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV‐SVR. According to the HCV treatment, 35 HCV‐SVR HCCs were classified into two groups: eight tumors with DAA (HCV‐SVR‐DAA) and 24 tumors with interferon (HCV‐SVR‐IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV‐SVR than in HCV‐positive tumors ( p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV‐SVR samples than in HCV‐positive samples ( p = 0.048). Among the patients with HCV‐SVR, the frequency of samples with TP53 mutations was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors ( p = 0.030). TP53 inactivation scores in HCV‐SVR‐DAA tumors were found to be significantly enhanced in comparison to HCV‐SVR‐IFN tumors ( p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV‐SVR‐DAA tumors. HCV‐SVR‐DAA was significantly associated with portal vein invasion ( p = 0.003) in comparison to HCV‐SVR‐IFN. Conclusion Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV‐SVR‐DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV‐positive tumors and HCV‐SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV‐SVR‐DAA tumors than in HCV‐SVR‐IFN tumors.

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Characteristics and Prognosis of De Novo Hepatocellular Carcinoma After Sustained Virologic Response

et al. 2021

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Hepatocellular carcinoma (HCC) can de novo develop in patients with chronic hepatitis C even after the achievement of sustained virologic response (SVR). We characterized de novo HCC after SVR, comparing it with HCC that developed in patients during persistent hepatitis C virus (HCV) infection. Characteristics, survival rates, and recurrence rates after curative treatment in 178 patients who developed initial HCC after SVR diagnosed between 2014 and 2020 were compared with those of 127 patients with initial HCC that developed during persistent HCV infection diagnosed between 2011 and 2015; HCC was detected under surveillance in both groups. HCC was less advanced and liver function worsened less in patients with SVR than in patients with persistent HCV. The survival rate after diagnosis was significantly higher for patients with SVR than for patients with persistent HCV (1‐, 3‐, and 5‐year survival rates, 98.2%, 92.5%, and 86.8% versus 89.5%, 74.7%, and 60.8%, respectively; P < 0.001). By contrast, the recurrence rate after curative treatment was similar between groups (1‐, 3‐, and 5‐year recurrence rates, 11.6%, 54.6%, and 60.4% versus 24.0%, 46.7%, and 50.4%, respectively; P = 0.7484). Liver function improved between initial HCC diagnosis and recurrence in patients with SVR ( P = 0.0191), whereas it worsened in the control group ( P < 0.001). In addition, patients with SVR could receive curative treatment for recurrence more frequently than patients with persistent HCV (80.4% versus 47.8%, respectively; P = 0.0008). Conclusion: Survival of patients with de novo HCC after SVR was significantly higher than that of patients in whom HCC developed during persistent HCV infection, despite similar rates of recurrence after curative treatment. A higher prevalence of curative treatment for recurrent HCC and improved liver function contributed to this result.

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Systematic review: current concepts and challenges for the direct‐acting antiviral era in hepatitis C cirrhosis

Cited by 135 publications

References 111 publications

Current and future challenges in HCV: insights from an Italian experts panel

Current and future challenges in HCV: insights from an Italian experts panel

Hepatocellular carcinoma after a sustained virological response by direct‐acting antivirals harborsTP53inactivation

Characteristics and Prognosis of De Novo Hepatocellular Carcinoma After Sustained Virologic Response

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