Histological assessment of the liver explant in transplanted hepatitis C virus patients achieving sustained virological response with direct‐acting antiviral agents

Putra, Juan; Schiano, Thomas D.; Fiel, M. Isabel

doi:10.1111/his.13453

Cited by 19 publications

(22 citation statements)

References 18 publications

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“…Until now, there have been limited published data on histologic changes in post-DAA-SVR livers. 4 In our large cohort of consecutive liver specimens from patients with chronic HCV, we show a significant decrease in inflammatory grade in post-DAA-SVR livers. However, 29% of DAA-SVR cases showed high grades (2 or 3þ) of inflammation, and 38% of DAA-SVR cases with cirrhosis continued to show a predominantly progressive pattern of fibrosis, which by definition requires septal inflammation to be present.…”

Section: Discussionmentioning

confidence: 62%

“…[1][2][3] Scant data exist on histologic changes seen after DAA therapy; studies have reported persistent inflammation and fibrosis in some patients, despite cure. 4 In addition, the impact of eliminating the virus on tumorigenesis remains controversial: achieving SVR may not necessarily correlate with a reduction in the risk of development or recurrence of hepatocellular carcinoma (HCC), especially in patients with cirrhosis. [5][6][7] During and after treatment, therapeutic response is determined by measuring serum HCV RNA levels using various nucleic acid amplification tests.…”

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confidence: 99%

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Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection

Celli

Saffo

Kamili

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Treatment of chronic viral hepatitis C (HCV) infection with direct-acting antiviral agents (DAAs) results in cure, or sustained viral response (SVR), in more than 90% of patients. However, there are subsets of patients who have persistent liver inflammation and fibrosis and develop hepatocellular carcinoma (HCC) despite achieving SVR. A possible reason for these phenomena may be the presence of virus particles in liver tissue but not blood, otherwise defined as occult infection. Objective.— To describe liver histologic findings following successful DAA therapy, test HCV RNA by (liver) tissue polymerase chain reaction in treated cases, and identify predictive markers for HCC development in treated cases. Design.— A total of 96 identified patients were divided into 4 groups, each differentiated by the presence or absence of SVR and HCC. Groups were compared for several clinicopathologic variables, including degree of inflammation and fibrosis, and the ‘directionality' of fibrosis in cirrhotic livers using the novel progressive-indeterminate-regressive scoring system. Results.— Overall, we found a significant decrease in inflammation in SVR patients. None of the patients showed regression of their cirrhosis following treatment. No evidence of occult HCV infection was seen in 40 livers tested, including 21 with HCC. The number of patients who developed HCC was similar in the SVR and non-SVR groups, and increased inflammation and fibrosis were associated with HCC development. Conclusions.— Following DAA-SVR there appears to be an overall decrease in inflammation, but the fibrosis tends to persist, at least in the short term (median follow-up of 20.2 months).

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Section: Discussionmentioning

confidence: 62%

mentioning

confidence: 99%

Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection

Celli

Saffo

Kamili

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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“…All the patients showed decreased MHAI scores and similar or slightly decreased fibrosis stages post‐DAA treatment, and histopathologic features of AIH were not seen (Tables and ). Several of these patients had persistence of mild portal lymphocytic inflammation after DAA treatment, which has been reported …”

Section: Resultsmentioning

confidence: 59%

Direct‐Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis

et al. 2019

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Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV‐positive (HCV+) study group that had elevated serum markers of AIH before starting direct‐acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre‐DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow‐up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.

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“…It is more difficult to assess post-SVR histopathological changes as we are no longer required to perform pre-treatment biopsies as we were in the IFN-era. However, when assessing histopathology within 2 years of treatment, though there is suggestion of fibrosis regression, persistent inflammatory activity has been observed despite the absence of the virus [20] .…”

Section: Hcv Treatment Regimensmentioning

confidence: 99%

Management of concomitant hepatocellular carcinoma and chronic hepatitis C: a review

Harrod¹,

Moctezuma‐Velázquez²,

Gürakar³

et al. 2019

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Our comprehensive review focuses on the treatment of hepatitis C virus in the context of hepatocellular carcinoma and vice versa, highlighting the ongoing complexity of this clinical scenario. There remain multiple unanswered questions when considering the management of these complex patients and, with a rapidly-changing treatment landscape for both chronic hepatitis C and hepatocellular carcinoma, these questions are only going to grow. Treatment timing, interactions and the impact of one disease condition on the other are vitally important, though guidance generally remains non-specific, suggesting that we make these decisions on a case-by-case basis. We focus on the current evidence for managing these cases, depending on disease stage and treatment type. BACKGROUND Hepatitis C virus (HCV) accounts for a third of all hepatocellular carcinoma (HCC) cases worldwide, with a 1%-8% annual risk of HCC development in cirrhotic HCV-infected patients [1-4] . The presence of cirrhosis greatly increases the risk of HCC development in HCV-positive patients, with the prominent pro-DECLARATIONS

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Histological assessment of the liver explant in transplanted hepatitis C virus patients achieving sustained virological response with direct‐acting antiviral agents

Abstract: Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.

Cited by 19 publications

References 18 publications

Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection

Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection

Direct‐Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis

Management of concomitant hepatocellular carcinoma and chronic hepatitis C: a review

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