RESUMEN
INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047). CONCLUSION: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Trasplante de Riñón , Activación Viral , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Factores de Riesgo , Adulto , Activación Viral/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/epidemiología , Hepatitis B/complicaciones , Antivirales/uso terapéutico , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Alpha fetoprotein (AFP) is the most widely used tumor marker for hepatocellular carcinoma (HCC). Nevertheless, few studies have investigated the prognostic factors of HCC patients with normal serum AFP levels. METHODS: We retrospectively enrolled 2198 patients with HCC and normal serum AFP levels (<20 ng/mL) from 2007 to 2020. Overall survival (OS) rates were calculated by the Kaplan-Meier method, and analyses of the prognostic factors were performed using a Cox proportional hazard model. RESULTS: Among the enrolled patients, 1385 (63%) patients were in the low-normal AFP group (serum AFP levels ≤7 ng/mL), and 813 (37%) patients were in the high-normal AFP group (serum AFP levels between 7 and 20 ng/mL). The high-normal AFP group had poorer liver functional reserve, more multiple tumors, and smaller tumor size compared to those in the low-normal AFP group. After a median follow-up of 32.4 months, 942 patients died, and the 5-year OS rate was 54.4%. The 5-year OS rates were 57.4% and 49.8% in the low-normal AFP group and high-normal AFP group, respectively (p = 0.001). A multivariate analysis showed the independent prognostic factors of poor OS were no anti-viral therapy, advanced albumin-bilirubin grades, the presence of vascular invasion, tumor size ≥5 cm, and non-curative treatment modalities. Serum AFP levels were not associated with OS according to the multivariate analysis. CONCLUSION: Liver functional reserve, anti-viral therapy, tumor size, vascular invasion, and treatment modalities, determined the outcomes of HCC patients with normal serum AFP levels, but serum AFP levels did not.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análisis , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Pronóstico , Estudios Retrospectivos , Biomarcadores de Tumor/sangreRESUMEN
BACKGROUND: For patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up. METHODS: In Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT)â >2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis. RESULTS: All patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation. CONCLUSION: Among HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur >3 months after end of therapy. CLINICAL TRIALS REGISTRATION: NCT02613871.
Asunto(s)
Coinfección , Hepatitis B , Hepatitis C Crónica , Hepatitis C , Antivirales , Bencimidazoles , ADN Viral , Fluorenos , Estudios de Seguimiento , Hepacivirus/genética , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis C/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Sofosbuvir/uso terapéutico , TaiwánRESUMEN
BACKGROUND: Although a patient care system may help nurses handle patients' requests or provide timely assistance to those in need, there are a number of barriers faced by nurses in handling alarms. METHODS: The aim of the study was to describe the implementation and experience of an innovative smart patient care system (SPCS). This study applied a cross-sectional descriptive design. We recruited 82 nurses from a medical center in Taiwan, with 25 nurses from a ward that had introduced an SPCS and 57 nurses from wards that used the traditional patient care system (TPCS). The major advantages of the SPCS compared to the TPCS include the specification of alarm purposes, the routing of alarms directly to the mobile phone; the capability of immediate communication via phone; and three-stage bed-exit alerts with low false alarm rate. RESULTS: Approximately 56% of nurses in the TPCS wards perceived that the bed-exit alert was easily ignorable, while this rate was reduced to 32% in the SPCS ward. The immediate communication via phone was considered as the most helpful function of the SPCS, with a weighted average score of 3.92/5, and 52% of nurses strongly agreed (5/5) that this function was helpful. The second-highest ranked function was the three-stage bed-exit alert, with an average score of 3.68/5, with approximately 24% of nurses strongly agreeing (5/5) that this function was helpful. The average response time using TPCS was 145.66 s while it was 59.02 s using the SPCS (P < .001). Among the 110 observed alarms in the SPCS ward, none of them were false bed-exit alarms. In comparison, among 120 observed alarms in the TPCS wards, 42 (35%) of them were false bed-exit alarms (P < .001). In this study, we found that 30.91% of alarms using SPCS were processed because nurses received and responded to the alert via mobile phone. CONCLUSIONS: A smart patient care system is needed to help nurses make more informed prioritization decisions between responding to alarms and ongoing tasks and finally assist them in adjusting their work in various situations to improve work efficiency and care quality.
Asunto(s)
Alarmas Clínicas , Estudios Transversales , Hospitales , Humanos , Atención al Paciente , Calidad de la Atención de SaludRESUMEN
BACKGROUND & AIMS: There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. METHODS: We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. RESULTS: All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log10 IU/mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase >2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation >2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV reactivation. The most common adverse events were headache, upper respiratory infection, and fatigue. CONCLUSIONS: In a prospective study, the combination of ledipasvir and sofosbuvir for 12 weeks produced a sustained virologic response in 100% of patients with HCV infection who were coinfected with HBV. Most patients had an increase in level of HBV DNA not associated with signs or symptoms. ClinicalTrials.gov no: NCT02613871.
Asunto(s)
Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Fluorenos/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis B/complicaciones , Hepatitis C/tratamiento farmacológico , Uridina Monofosfato/análogos & derivados , Adulto , Anciano , Antivirales/efectos adversos , Bencimidazoles/efectos adversos , Coinfección , ADN Viral/genética , Femenino , Fluorenos/efectos adversos , Hepacivirus/genética , Hepatitis B/diagnóstico , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral , Sofosbuvir , Respuesta Virológica Sostenida , Taiwán , Factores de Tiempo , Resultado del Tratamiento , Uridina Monofosfato/efectos adversos , Uridina Monofosfato/uso terapéutico , Carga ViralRESUMEN
BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients. METHODS: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE. RESULTS: Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09-1.84), 1.51 (95% CI, 1.11-2.06), and 3.01 (95% CI, 1.78-5.10) for patients with 30-120 cDDDs, 120-365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE. CONCLUSIONS: Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.
Asunto(s)
Encefalopatía Hepática/epidemiología , Encefalopatía Hepática/etiología , Cirrosis Hepática/complicaciones , Inhibidores de la Bomba de Protones/administración & dosificación , 2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Adulto , Anciano , Estudios de Casos y Controles , Esomeprazol/administración & dosificación , Femenino , Humanos , Incidencia , Seguro de Salud/estadística & datos numéricos , Lansoprazol/administración & dosificación , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Pantoprazol , Rabeprazol/administración & dosificación , Taiwán/epidemiologíaRESUMEN
BACKGROUND AND AIM: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. METHODS: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. RESULTS: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9-99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8-100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. CONCLUSIONS: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.
Asunto(s)
Benzazepinas/administración & dosificación , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Imidazoles/administración & dosificación , Indoles/administración & dosificación , Isoquinolinas/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carbamatos , Estudios de Cohortes , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinas , República de Corea , Federación de Rusia , Taiwán , Resultado del Tratamiento , Valina/análogos & derivados , Adulto JovenRESUMEN
BACKGROUND & AIMS: In Taiwan, patients with chronic hepatitis C virus (HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection ± compensated cirrhosis. METHODS: In this multicentre, open-label, phase 3b (NCT02021643) study, 87 patients (n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were also collected. RESULTS: All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment-emergent adverse events (AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon. CONCLUSIONS: The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Ribavirina/administración & dosificación , Sofosbuvir/administración & dosificación , Adulto , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Taiwán , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND AND AIM: Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS: In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS: The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS: Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.
Asunto(s)
Bencimidazoles/administración & dosificación , Carbamatos/administración & dosificación , Fluorenos/administración & dosificación , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Sofosbuvir/administración & dosificación , Adulto , Anciano , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Taiwán , Resultado del TratamientoRESUMEN
BACKGROUND: An unmet need exists for interferon-free and ribavirin-free treatments for chronic hepatitis C virus (HCV) infection. In this study, we assessed all-oral therapy with daclatasvir (NS5A replication complex inhibitor) plus asunaprevir (NS3 protease inhibitor) in patients with genotype 1b infection, including those with high unmet needs or cirrhosis, or both. METHODS: We did this phase 3, multicohort study (HALLMARK-DUAL) at 116 sites in 18 countries between May 11, 2012, and Oct 9, 2013. Patients were adults with chronic HCV genotype 1b infection who were treatment-naive; previous non-responders to peginterferon alfa plus ribavirin; or medically ineligible for, previously intolerant of, or ineligible for and intolerant of peginterferon alfa plus ribavirin. Treatment-naive patients were randomly assigned (2:1 ratio) by an interactive voice-response system with a computer-generated random allocation sequence (stratified by cirrhosis status) to receive daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily or placebo for 12 weeks. Patients and investigator sites were masked to treatment assignment and HCV RNA results to the end of week 12. The treatment-naive group assigned to daclatasvir plus asunaprevir continued open-label treatment to the end of week 24; participants assigned to placebo entered another daclatasvir plus asunaprevir study. Non-responders and ineligible, intolerant, or ineligible and intolerant patients received open-label daclatasvir plus asunaprevir for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12. Efficacy analyses were restricted to patients given daclatasvir plus asunaprevir. This trial is registered with ClinicalTrials.gov, number NCT01581203. FINDINGS: This study included 307 treatment-naive patients (205 received daclatasvir plus asunaprevir and 102 received placebo; all randomly assigned patients received the intended treatment), 205 non-responders, and 235 ineligible, intolerant, or ineligible and intolerant patients. Daclatasvir plus asunaprevir provided sustained virological response in 182 (90%, 95% CI 85-94) patients in the treatment-naive cohort, 168 (82%, 77-87) in the non-responder cohort, and 192 (82%, 77-87) in the ineligible, intolerant, or ineligible and intolerant cohort. Serious adverse events occurred in 12 (6%) patients in the treatment-naive group; 11 (5%) non-responders, and 16 (7%) ineligible, intolerant, or ineligible and intolerant patients; adverse events leading to discontinuation (most commonly reversible increases in alanine or aspartate aminotransferase) occurred in six (3%), two (1%), and two (1%) patients, respectively, with no deaths recorded. Grade 3 or 4 laboratory abnormalities were uncommon, with low incidences of aminotransferase increases during the first 12 weeks with daclatasvir plus asunaprevir and placebo in treatment-naive patients (≤2% each). INTERPRETATION: Daclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive, non-responder, and ineligible, intolerant, or ineligible and intolerant patients, and was well tolerated in patients with HCV genotype 1b infection. These results support the use of daclatasvir plus asunaprevir as an all-oral, interferon-free and ribavirin-free treatment option for patients with HCV genotype 1b infection, including those with cirrhosis. FUNDING: Bristol-Myers Squibb.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/uso terapéutico , Isoquinolinas/uso terapéutico , Sulfonamidas/uso terapéutico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Carbamatos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Imidazoles/administración & dosificación , Isoquinolinas/administración & dosificación , Masculino , Persona de Mediana Edad , Pirrolidinas , ARN Viral/sangre , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Valina/análogos & derivados , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: In cirrhosis, hypersensitivity to benzodiazepines (BZD) and precipitating hepatic encephalopathy (HE) have been reported. The aim of this study was to evaluate the safety, economic impact and modifiable factors that are associated with the excess risk of BZD-associated HE in cirrhotic patients. METHODS: Between July 2005 and March 2012, 1,612 Chinese cirrhotic patients with and without using long-t 1/2-BZD or short-t 1/2-BZD were enrolled and followed up for 6 months. RESULTS: Among BZD users, the per-person HE-related healthcare utilization and medical costs were found to have progressively increased from 2005 to 2012. Cirrhotic BZD users had a higher percentage of smoking, alcohol drinking, simultaneous consumption of non-BZD drugs, and had a higher incidence of non-cirrhotic chronic illness than non-BZD users. Multivariate analysis indicated that hypoalbuminemia (<3 g/dL), long-acting (t 1/2 > 12-h), high-dosage (>1.5 defined daily dose equivalents) and long-duration (>2-months) BZD use, carrier of variant genotypes (AG + GG) of GABRA 1 (rs2290732) and having the wild genotype (TT) of GABRG 2 (rs211037) were significant predictors of the development of BZD-associated HE in cirrhotic patients. Additionally, synergistic effects of the above significant predictors on BZD-associated HE risk could be identified. CONCLUSIONS: Our study confirms the clinical and economic impact of BZD-associated HE in cirrhotic BZD-users. Accordingly, extra caution is needed when treating cirrhotic BZD users with the above risk factors in order to avoid the BZD-associated HE in cirrhotic patients.
Asunto(s)
Ansiedad/tratamiento farmacológico , Benzodiazepinas/efectos adversos , Costos de la Atención en Salud/estadística & datos numéricos , Servicios de Salud/estadística & datos numéricos , Encefalopatía Hepática/inducido químicamente , Hipnóticos y Sedantes/efectos adversos , Cirrosis Hepática/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/etiología , Benzodiazepinas/uso terapéutico , China , Esquema de Medicación , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Costos de la Atención en Salud/tendencias , Servicios de Salud/economía , Encefalopatía Hepática/economía , Encefalopatía Hepática/genética , Encefalopatía Hepática/terapia , Humanos , Hipnóticos y Sedantes/uso terapéutico , Análisis de Intención de Tratar , Cirrosis Hepática/psicología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND/AIMS: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. METHODS: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. RESULTS: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. CONCLUSION: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizaje Automático , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Medición de Riesgo , AdultoRESUMEN
BACKGROUND: The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence. METHODS: Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models. RESULTS: The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors. CONCLUSION: This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Carcinoma Hepatocelular/patología , Interferones/uso terapéutico , Antivirales/uso terapéutico , Neoplasias Hepáticas/patología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , alfa-Fetoproteínas , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Factores de RiesgoRESUMEN
INTRODUCTION: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC. METHODS: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS. RESULTS: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001). DISCUSSION: PNI had the best performance in predicting the OS for patients with very early-stage HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Estadificación de Neoplasias , Evaluación Nutricional , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Anciano , Biomarcadores de Tumor/sangre , Bilirrubina/sangre , Tasa de Supervivencia , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Cirrosis Hepática/patología , Modelos de Riesgos Proporcionales , Recuento de Plaquetas , Aspartato Aminotransferasas/sangre , Estudios de SeguimientoRESUMEN
BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a reversible neuropsychiatric disorder in cirrhotic patients. The cognitive dysfunction and increased accidental falls in HE and osteodystrophy in cirrhotic patients may contribute to orthopedic fractures. This study investigated the fracture incidence and risk factors in cirrhotic patients with HE. METHODS: In total, 3764 cirrhotic patients with HE were identified from the Taiwan National Health Insurance database between 2000 and 2009. The fracture incidence of the HE patients was compared with that of 3764 age-, sex-, and comorbidity-matched cirrhotic patients without HE and non-cirrhotic controls. Cox proportional hazard models were used to estimate the risk of fracture in the HE patients. RESULTS: Cirrhotic patients with and without HE had comparable increased risks of fracture (p <0.05) and cumulative incidences of fracture than controls (log-rank p <0.001). The estimated fracture rates were 7.09% for the HE group, 7.72% for the cirrhosis without HE group, and 4.05% for the controls, during the 18-month follow-up. The HE group had a higher incidence rate of skull fractures (IRR=2.61, 95% CI 1.04-6.57), but a lower rate of upper limb fractures (IRR=0.45, 95% CI 0.29-0.70) than the cirrhosis without HE group. Alcoholism, heart failure, and cerebrovascular disease were associated with increased risk of fracture in HE patients. CONCLUSIONS: Cirrhotic patients, with or without HE, are at an increased risk of orthopedic fractures. Skull fractures, rather than fractures in weight-bearing bones, are more frequently observed in HE patients, particularly those with comorbidities.
Asunto(s)
Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Cirrosis Hepática/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/complicaciones , Encefalopatía Hepática/complicaciones , Humanos , Incidencia , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND AIM: Endoscopic screening for esophageal varices (EVs) is expensive and invasive. Besides traditional noninvasive markers, we explore additional candidate markers including portal hypertension serum marker-soluble CD136 (sCD163) and genetic variants of splanchnic vasodilatation and revascularization pathways for prediction of EVs in cirrhotic patients. METHODS: A total of 951 cirrhotic patients without history of variceal bleeding and an independent validation cirrhotic cohort were enrolled to evaluate the association between the presence of EVs and patients' clinical and genetic characteristics. RESULTS: Cirrhotic patients with EVs had higher serum sCD163 and heme oxygenase-1 (HO-1) level, which was positively correlated with the number of risk alleles of HO-1 (S, A), vascular endothelial growth factor (VEGF [G, T]) and VEGF receptor-2 (VEGFR2 [Ile]) genes, than those without EVs. Multivariate analysis showed that EVs in cirrhotic patients was predicted by low platelet count, high sCD163 level, splenomegaly, HO-1 AS and the VEGF GT risk haplotypes. Additive effects in relation to predict EVs were observed in the simultaneous presence of HO-1 AS and VEGF GT risk haplotypes. Combining low platelet count with high sCD163/risk haplotypes significantly increased the predictability of EVs. Furthermore, cirrhotic patients carrying both HO-1 AS and VEGF GT risk haplotypes had lower probability of being free of EVs bleeding compared to patients without above risk haplotypes. CONCLUSIONS: This study suggested that high sCD163 levels and genetic risk variants are additional markers that can be combined with low platelet count to optimize assessment of EVs and bleeding in cirrhotic patients.
Asunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Várices Esofágicas y Gástricas/sangre , Várices Esofágicas y Gástricas/genética , Hemorragia Gastrointestinal/genética , Cirrosis Hepática/sangre , Cirrosis Hepática/genética , Recuento de Plaquetas , Receptores de Superficie Celular/sangre , Anciano , Alelos , Biomarcadores/sangre , Várices Esofágicas y Gástricas/etiología , Femenino , Haplotipos , Hemo-Oxigenasa 1/sangre , Hemo-Oxigenasa 1/genética , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neovascularización Patológica/genética , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Esplenomegalia/complicaciones , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Vasodilatación/genéticaRESUMEN
BACKGROUND: The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan. METHODS: Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models. RESULTS: The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047). CONCLUSION: Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients. METHODS: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0. RESULTS: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score. CONCLUSION: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.
RESUMEN
BACKGROUND: For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. METHODS: Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. RESULTS: The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. CONCLUSION: For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Seguridad , Sofosbuvir/administración & dosificación , Resultado del Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , TaiwánRESUMEN
Background: The response rate to sorafenib is limited for unresectable hepatocellular carcinoma (HCC). Little is known about the long-term outcomes of objective responders. The role of second-line therapies on the survival of sorafenib-responders is unclear. We aimed to delineate the long-term outcomes and the role of subsequent treatment after responding to sorafenib. Methods: From September 2012 to December 2019, 922 patients who received sorafenib treatment for unresectable HCC were retrospectively reviewed. Of these, 21 (2.3%) achieved a complete response (CR) and 54 (5.9%) had a partial response (PR) based on mRECIST criteria. Factors associated with survivals were analyzed. Results: During the median follow-up of 35.3 months, the median duration of response was 18.3 months (range: 2.3-45.5) for patients achieving CR and 10.0 months (range: 1.9-60.3) for PR. The median overall survival (OS) was 39.5 months [95% confidence interval (CI): 28.4-50.5] including values not yet estimable for CR and 25.8 months for PR. Patients who experienced treatment-related adverse events (TRAEs) had better median OS than those without (44.9 versus 18.1 months, p = 0.003). Eventually, 53 patients developed tumor progression; 30 patients received second-line systemic treatment including nivolumab (n = 8), regorafenib (n = 15), and chemotherapy (n = 7). Sorafenib-nivolumab sequential therapy provided the best median OS versus sorafenib-regorafenib and sorafenib-chemotherapy in these patients (55.8, 39.5, and 25.5 months), respectively. Conclusions: The response is durable for advanced HCC patients with CR or PR to sorafenib. Subsequent immunotherapy seems to provide the best survival. This information is important for characterizing outcomes of sorafenib-responders and the choice of sequential treatment.