scholarly journals Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243473
Author(s):  
Kazumichi Abe ◽  
Hiroto Wakabayashi ◽  
Haruo Nakayama ◽  
Tomohiro Suzuki ◽  
Masahito Kuroda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Survival Rates ◽  
Virologic Response ◽  
Female Ratio ◽  
Factors Affecting ◽  
Direct Acting Antiviral ◽  
Compensated Cirrhosis ◽  
Male Female Ratio ◽  
Direct Acting

The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.

scholarly journals Lymphocyte Landscape after Chronic Hepatitis C Virus (HCV) Cure: The New Normal

2020 ◽  
Vol 21 (20) ◽  
pp. 7473
Author(s):  
Alip Ghosh ◽  
Sara Romani ◽  
Shyam Kottilil ◽  
Bhawna Poonia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Virologic Response ◽  
Viral Clearance ◽  
Liver Pathology ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Immune Defects ◽  
The Impact

Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (>95%) proportions of patients. These treatments became available 6–7 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system’s capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.

scholarly journals Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2257
Author(s):  
Joji Tani ◽  
Tomonori Senoh ◽  
Akio Moriya ◽  
Chikara Ogawa ◽  
Akihiro Deguchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Treatment ◽  
Survival Rates ◽  
Long Term Outcomes ◽  
Recurrence Rates ◽  
Virus Eradication ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Hcc Recurrence

There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924–8.207, p = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016–1.077, p = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively (p = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.

scholarly journals Post-treatment Mac-2-Binding Protein is a Useful Predictor of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication

2021 ◽  
Author(s):  
Shunsuke Sato ◽  
Hironori Tsuzura ◽  
Yuji Kita ◽  
Yuji Ikeda ◽  
Daishi Kabemura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Binding Protein ◽  
Virologic Response ◽  
Virus Eradication ◽  
Direct Acting Antiviral ◽  
Noninvasive Biomarker ◽  
Direct Acting

Abstract Background and aims: Recent advances of direct-acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development not rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+-M2BP level and HCC development after the achievement of an SVR is unclear. Methods: We examined the association between WFA+-M2BP and HCC development in 552 HCV patients who achieved an SVR (Interferon [IFN]-based therapy, n=228; IFN-free therapy, n=294). Results: Multivariate analysis revealed that a high WFA+-M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR]=1.215, P=0.020), low platelet counts (HR=0.876, P=0.037) and old age (HR=1.073, P=0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that an WFA+-M2BP level at SVR24 of ≥1.62 cut off index (COI) was the cut-off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501-45.092, P<0.001). The 3- and 5-year cumulative incidences of HCC were 0.7% and 0.7% in patients with low WFA+-M2BP at SVR24 (<1.62 COI), and 4.8% and 12.4% in patients with high WFA+-M2BP (≥1.62 COI) were, respectively (P<0.001).Conclusion: The assessment of liver fibrosis using the WFA+-M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN-free therapy era.

scholarly journals Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262267
Author(s):  
Seiichi Mawatari ◽  
Kotaro Kumagai ◽  
Kohei Oda ◽  
Kazuaki Tabu ◽  
Sho Ijuin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Proportional Hazards ◽  
Antiviral Treatment ◽  
Virologic Response ◽  
Cox Proportional Hazards ◽  
Direct Acting Antiviral ◽  
History Of ◽  
Direct Acting

Background The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. Methods The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. Results Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) <3.9 g/dL (HR: 2.305) were associated with HCC development. Especially, EOT-AFP ≥5.3 ng/mL was associated with HCC development after 3 years from EOT (HR: 6.237). Among patients who developed HCC, AFP did not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. Of these 5 factors, EOT-AFP ≥5.3 ng/mL was scored as 2 points; the others were scored as 1 point. The 4-year cumulative carcinogenesis rate for patients with total scores of 0–2, 3–4, and 5–6 points were 0.6%, 11.9%, and 27.1%, respectively (p<0.001). Conclusions EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. The combination of EOT-AFP, age, sex, HA, and EOT-Alb is important for predicting carcinogenesis.

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