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BACKGROUND/AIMS: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
Assuntos
Antivirais , Carcinoma Hepatocelular , Hepatite C Crônica , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Hepáticas , Metformina , Humanos , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Masculino , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Metformina/uso terapêutico , Feminino , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Antivirais/uso terapêutico , Taiwan/epidemiologia , Incidência , Idoso , Adulto , Fatores de Risco , Modelos de Riscos Proporcionais , Diabetes MellitusRESUMO
BACKGROUND & AIMS: Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS: Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS: Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS: Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS: The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.
Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus , Hepatite C Crônica , Neoplasias Hepáticas , Metformina , Humanos , Masculino , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Antivirais/uso terapêutico , Estudos de Coortes , Metformina/uso terapêutico , Incidência , Taiwan/epidemiologia , Estudos Retrospectivos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Cirrose Hepática/complicações , Resposta Viral Sustentada , Obesidade/complicaçõesRESUMO
BACKGROUND: Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. METHODS: Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12â 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. RESULTS: Twenty-four patients developed new-onset major psychoses during 67â 554 person-years (3.6 per 10â 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, Pâ =â .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio =â 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (Pâ =â .02). CONCLUSIONS: Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.
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Most foreign laborers in Taiwan come from Southeast Asia, where public health is not as well funded as in Taiwan, and parasitic infections are still common. Therefore, we recruited foreign laborers to undergo examination for parasitic infection to determine the infection conditions and follow-up conditions in foreign laborers whose stools were found to be abnormal. A total of 7,360 foreign laborers were enrolled for stool examination in our hospital, and the merthiolate iodine formaldehyde method was used to diagnose intestinal parasite infection. In total, 331 (4.5%) foreign laborers were found to be infected, and Blastocystis hominis was identified as the most prevalent intestinal parasite (2.54%), followed by Trichuris trichiura (0.54%) and hookworm (0.53%). Parasite infection rates among laborers of different nationalities were also significantly different (p < 0.001). Forty-two intestinal-parasite-infected foreign laborers received anti-parasitic therapy in our hospital, and treatment was successful. Among the 154 intestinal-parasite-infected foreign laborers who did not receive treatment in our hospital but were later re-examined, 132 were parasite-free. B. hominis has been the most prevalent intestinal parasite infecting foreign laborers in Taiwan ever since it was added to the list of infections to be screened for stool examination by the Taiwan Centers for Disease Control in 2002. It is important to closely monitor, control and treat parasite-infected foreign laborers to minimize the danger to public health.