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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

Abstract Background No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). Methods A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. Results The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (

Abstract Lenvatinib has been approved as one of the first‐line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non‐inferior to sorafenib. Previous studies have shown well‐controlled viremia contributes to the prognosis of HCC patients receiving first‐line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first‐line lenvatinib treatment in our institute were assessed. High‐effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct‐acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well‐controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV‐related HCC (HBV‐HCC) and 44 patients with HCV‐related HCC (HCV‐HCC), respectively. Progression‐free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV‐HCC patients and 88.4% of the HCV‐HCC patients had well‐controlled viremia, and their PFS (8.8 vs. 3.1 months, p

Abstract Background Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. Methods We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan–Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). Results In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1–2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. Conclusion The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.

Abstract Background The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC). Methods We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan–Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child–Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA

Background/Purpose: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. Methods: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. Results: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. Conclusion: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

Background: Hyperendemic townships of hepatitis C virus (HCV) infection should devote extra efforts to eliminate HCV. We aimed to evaluate efficacy of the screening and linkage to care in two HCV hyperendemic townships. Methods: Village-to-village HCV screening using anti-HCV reflex HCV Ag test was conducted in two HCV hyperendemic rural townships (Lioujiao and Yijhu). All residents aged 30 years or older were invited. Those patients detected as infected were referred to nearby hospitals or clinics in Lioujiao and to an accessible outreach hepatology clinic in Yijhu. Results: The populations of Lioujiao and Yijhu townships at time of survey were 18,389 and 14,787 with 6086 (33.1%) and 4604 (31.1%) having ever been previously screened, and 1517 and 1071 responded to this screening respectively. Their crude screening coverage rates were 41.5% and 38.5%, and adjusted screening coverage rates were 54.3% and 94.6% respectively. The prevalence rates of anti-HCV and HCV Ag were 17.9% and 11.9% in Lioujiao, and 9.2% and 5.6% in Yijhu respectively, with their rates of antigenemia (HCV Ag/anti-HCV) being 62.1% and 60.6% respectively. Numbers needed to test (NNT) to find a candidate for anti-viral treatment were 9 and 18. For linkage to care, treatment rate by referral (Lioujiao) was slightly lower than by accessible outreach hepatology clinic (Yijhu) (84.9% vs. 93.3%, p = 0.093). Overall successful sustained virological response rate at week 12 was 98.2% (161/164) in outreach hepatology clinic. Conclusion: Since NNT was low, it was worthwhile conducting intensive screening in these hyperendemic townships. For high treatment rate, accessible outreach hepatology clinic is feasible especially in areas without adequate medical resources.

Background/Purpose: This study is to use albumin-bilirubin (ALBI) grade and up-to-7 (UT7) criteria to assess outcomes of patients with intermediate stage hepatocellular carcinoma (HCC) after transarterial (chemo)embolization (TA(C)E). Methods: Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TA(C)E were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. Results: A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria (UT7 (−)). There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 (UT7 (+)) and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 −/+, patients were classified into six groups as ALBI grade I plus UT7 (−), II plus UT7 (−), III plus UT7 (−), I plus UT7 (+), II plus UT7 (+), and III plus UT7(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7 (−) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7 (−) and I plus UT7 (+) were ALBI-U class II, and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p

Abstract To determine whether liver stiffness (LS) and fibrosis‐4 (Fib‐4) index were useful in assessing the occurrence of liver‐related complications (LRC) in chronic hepatitis C (CHC) patients after direct‐acting antivirals (DAAs) had been administered. This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. A total of 697 (male/female: 294/403, mean age: 63.8 year) patients with measured LS and complete lab data at SVR were enrolled, followed, and analyzed. In a median follow‐up of 21.4 months after SVR, 39 patients developed LRC including 28 with hepatocellular carcinoma (HCC), with the 30‐month cumulative incidence of LRC and HCC being 7.7% and 5.1%, respectively. Predictions of occurrence of LRC and HCC were 0.820 and 0.774 for LS, and 0.775 and 0.737 for Fib‐4, with optimal cutoffs of LS and Fib‐4 being 14.5 kPa and 2.9 for LRC prediction. In multivariate analysis, LS was associated with the occurrence of LRC (hazard ratio: 3.97, 95% confidence interval [1.866, 8.446], p

Abstract Sorafenib is the recommended first‐line treatment option for patients with advanced hepatocellular carcinoma (HCC). Hepatitis C virus (HCV)‐related advanced HCC (HCV–HCC) seemed to have a better response than hepatitis B virus (HBV)‐related HCC (HBV–HCC) in sorafenib use, but it was undetermined. Hence, we aimed to investigate the effect of sorafenib between HBV–HCC and HCV–HCC patients in Taiwan. From August 2012 to December 2016, 575 consecutive advanced HCC patients received sorafenib under the reimbursement of Taiwan national health insurance in our hospital. Radiologic assessment was performed at a 2‐month interval. Those patients with tumor progression or liver function deterioration were disallowed for further sorafenib use. Patients with HBV or HCV infection were, retrospectively, enrolled and followed till December 2018. There were 277 (62.4%) HBV–HCC patients and 167 (37.6%) HCV–HCC patients. Before sorafenib, 192 (69.3%) HBV–HCC patients who had used nucleoside analogs (NAs) for HBV management, whereas only 5 (3%) HCV–HCC patients received interferon‐based antiviral therapy. Overall survival (OS) of HCV–HCC patients was significantly superior to HBV–HCC patients without NAs (8.8 months vs. 4.9 months, p = 0.006), but was noninferior to HBV–HCC patients with NAs (8.8 months vs. 10.7 months, p = 0.54). Using propensity score matching, progression‐free survival (2.0 months vs. 2.1 months, p = 0.374) and OS (10.5 months vs. 9.6 months, p = 0.746) between HBV–HCC and HCV–HCC groups were not different. Antiviral therapy might increase survival benefits of advanced HBV–HCC patients underwent sorafenib use, leading to a comparable OS to HCV–HCC patients in Taiwan.

Liver abscess formation is one of the major complications following radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC). Clostridium perfringens is a rare but fatal (mortality rate: 70–100%) organism that could lead to severe sepsis. We presented a case where a 63-year-old woman with diabetes mellitus, hypertension, chronic hepatitis B-related cirrhosis in Child-Pugh class A and HCC with initial TNM stage II who had undergone 2 sessions of transarterial chemoembolization. RFA was performed for 4 small HCC due to poor effect of previous transarterial chemoembolization. However, all 4 treated tumors developed liver abscesses presenting with septic shock within 1 day. Aspirated abscesses and blood culture both yielded C. perfringens infection. After intensive care, optimal intravenous antibiotic, and abscesses aspiration, the patient recovered successfully. All tumors achieved complete response during the follow-up period without local recurrence. The clinical presentations and risk factors of C. perfringens-related liver abscess after RFA will be discussed in this manuscript.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan had established a management consensus guideline in 2016. The current recommendations focus on updating critical issues regarding the management of HCC, including surveillance, diagnosis, and systemic treatment. For surveillance, the updated guideline suggests the role of dynamic computed tomography or magnetic resonance imaging and contrast-enhanced ultrasound (CEUS) in selected patients. For diagnosis, this update incorporates CEUS and recognizes the role of gadoxetic acid–enhanced magnetic resonance imaging. For systemic therapy, the updated guideline summarizes the multiple choices of targeted therapy, immune checkpoint inhibitors, and the combination of both. Through this update of the management consensus guideline, patients with HCC can benefit from receiving optimal diagnostic and therapeutic modalities.

Abstract Curative resection is recommended for patient with early stage hepatocellular carcinoma (HCC), however, the prognosis is limited by high recurrence rate. This study was to investigate liver stiffness (LS) and metabolic factor in prediction of HCC recurrence for patients with early stage HCC who had undergone curative resection. Consecutive patients with suspicion of HCC who had undergone curative resection were prospectively enrolled. Transient elastography was performed to determine LS pre-operatively. The demographics, clinical characteristics and histological findings were recorded. All patients were followed up regularly until recurrence, death or last visit. Ninety-four patients with early stage HCC were enrolled. LS positively correlated with fibrosis stage (r = 0.666). In a median follow-up of 3.2 years, forty patients developed recurrences including 22 recurrences after 1-year post resection. The 5-year cumulative recurrence rate was 44.2%. LS was the independent factor associated with recurrence. Patients with LS > 8.5 kPa had higher 5-year cumulative recurrence rate (59.8% vs 25.1%, p = 0.007). For the prediction of recurrence after 1-year post resection, LS > 8.5 kPa (hazard ratio 2.72) and homeostatic model assessment for insulin resistance index (HOMA-IR) (hazard ratio 1.24) were independent factors in multivariate analysis. Those patients with both LS > 8.5 kPa and HOMA-IR > 2.3 had the highest recurrence rate after 1-year post resection.

Background/Purpose: Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. Methods: 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. Results: Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. Conclusion: Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.

Abstract The utility of primary culture originated from the residual aspiration specimens to predict outcomes of hepatocellular carcinoma patients receiving curative treatment was investigated. A total of 105 American Joint Committee on Cancer TNM stage I or II patients were included. The culture results were determined at the 28th of culture and were divided into rapid proliferation of cancer cells alone, rapid proliferation of both cancer cells and cancer‐associated fibroblasts, rapid proliferation of cancer‐associated fibroblasts alone, slow proliferation, and no outgrowth of plating specimens. Our results showed that outgrowths of cultured cells from plated particles were achieved in 98.1% of patients. Sixty‐nine patients (65.7%) showed rapid proliferation of cultured cells (11 rapid proliferation of cancer cells alone, 17 rapid proliferation of both cancer cells and cancer‐associated fibroblasts, and 41 rapid proliferation of cancer‐associated fibroblasts alone). There was no significant difference in the incidence of recurrence or survival between patients with normal and abnormal serum alpha‐fetoprotein levels, chronic hepatitis B and chronic hepatitis C, TNM stage I and stage II, histological high‐grade and low‐grade hepatocellular carcinoma, and between patients treated by operative resection and local abrasion. Only patients with rapid proliferation of cancer cells ± rapid proliferation of cancer‐associated fibroblasts showed significantly higher incidence of recurrence than patients with other growth types (P = .0482), but there was no significant difference in survival between two groups. In conclusion, primary culture using this method is clinically feasible and can be applied to predict recurrence of hepatocellular carcinoma patients receiving curative treatment.

Abstract Results of fine‐needle aspiration of hepatic nodules may be equivocal to confuse clinical judgment. The utility of primary culture of aspiration residual specimens to improve the accuracy in differential diagnosis between hepatocellular carcinoma and benign lesions was investigated. A total of 337 patients (hepatocellular carcinoma proven by aspiration 277, by other modalities 35, benign nodules 25) were included. The growth patterns of cancer cells at the 14th day of primary culture from aspiration proven hepatocellular carcinoma patients were applied as criteria for analysis. Hepatocellular carcinoma proven by aspiration showed higher incidence of outgrowth of cancer cells than those not proven by aspiration or the incidence of outgrowth of hepatocyte antigen positive cells in benign lesions (all P 2 cm. Using at least one positive result of growth patterns or aspiration as item for differential diagnosis increased the sensitivity, negative predictive value and accuracy, but little decreased the specificity and positive predictive value as compared with aspiration results alone in nodules measuring either ≤ or >2 cm. In conclusion, the growth patterns at the 14th day of primary culture can be applied for dynamic interpretation of the specimens to improve the diagnostic accuracy of fine‐needle aspiration between hepatocellular carcinoma and benign lesions.

Background and purpose: Hepatitis C virus (HCV) core antigen is highly sensitive and specific in viremic HCV diagnosis. This study evaluated the cost-effectiveness of HCV core antigen (HCVcAg) in community-based screening for active HCV infection. Methods: Between 2017/07 and 2018/07, community-based screenings for active HCV infection with two-step (anti-HCV for screening and HCVRNA for diagnosis) and one-step processes (HCVcAg for screening and diagnosis) were conducted in two districts in Kaohsiung City. While HCVcAg test was positive at ≥3 fmol/L, the lowest level of HCV-RNA detection was 12 IU/mL. We analyzed the cost-effectiveness of two algorithms in identifying active HCV infection. Results: There were two large-scale screenings using the two-step process with a total of 2452 residents enrolled; while six hundred and forty-four residents participated in continuous small-scale screening with the one-step process. The prevalence of anti-HCV and positive HCVcAg was 3.4% and 2.8%. The viremic rate was 1.4% and 2.8% for two- and one-step processes (p

Background: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. Materials and methods: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. Results: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). Conclusions: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.

BackgroundLenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world.MethodsWe retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups.ResultsA total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3–0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively.ConclusionsIn clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of HCC continues to increase after long-term anti-viral therapy. The relationship between HBcrAg and HCC development in CHB-related liver cirrhosis (LC) patients undergoing long-term anti-viral therapy is still unclear. This study enrolled 1108 treatment-naïve CHB patients diagnosed with HBV-related LC receiving NUC therapy from April 1999 to February 2015. The baseline biomarkers, disease history, and following results were collected by the hospital. Among the 1108 patients, 219 developed HCC within a median follow-up period of 6.85 years. A multivariable Cox regression model was used, with adjustment for age, gender, FIB-4, DM, and HBsAg-HQ. The adjusted hazard ratios for the HBcrAg tertile levels were 1.70 (95%CI: 1.21, 2.39) and 2.14 (95%CI: 1.50, 3.05) for levels 3.4–4.9 and >4.9 logU/mL, respectively, compared with levels ≤3.4. The effect of the HBcrAg level on HCC incidence was found to be significantly modified by HBsAg-HQ, where lower HBsAg-HQ (≤ 3) values were associated with a significantly higher risk, but HBsAg-HQ levels >3 were not. Our results highlight that, after adjustment for potential confounding factors, patients with CHB-related LC and higher HBcrAg levels are at significant risk for HCC development, even while undergoing long-term effective anti-viral therapy. The HBcrAg level is therefore an independent risk factor for HCC development, especially for patients with HBsAg-HQ levels

Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing liver resection. Vietnamese patients had a significantly higher ratio of hepatitis B virus (HBV) (p < 0.001) and a lower ratio of hepatitis C virus (HCV) (p < 0.001) and non-B non-C than Taiwanese patients. Among patients with HBV or non-B non-C, the mean age was younger in Vietnam than in Taiwan (p < 0.001, p = 0.001, respectively). The HCC patients in Vietnam had significantly higher serum alpha-fetoprotein (AFP) levels (p < 0.001), larger tumors (p < 0.001), and a higher ratio of macrovascular invasion (p < 0.001) and extrahepatic metastasis (p < 0.001), compared to those in Taiwan. Patients treated in Vietnam had a higher tumor recurrent rate (p < 0.001), but no difference in overall survival was found between both groups. In subgroup analysis, the recurrent rate of HCC was the highest in patients with dual HBV/HCV, followed by HCV or HBV, and non-B non-C (p < 0.001). In conclusion, although the viral etiology and clinicopathological characteristics of HCC differed, postoperative overall survival was comparable between patients in Taiwan and Vietnam.

Abstract Hepatocellular carcinoma (HCC) development is ameliorated with nucleos(t)ide agent (NA) therapy for hepatitis B virus (HBV)‐related cirrhosis patients. This study investigates whether liver stiffness (LS) measurement at complete virological response (CVR) was useful in predicting HCC development. Between July 2006 and August 2016, HBV‐related cirrhosis patients with potent NA (entecavir/tenofovir) with the first LS measurement during CVR and with serial LS were enrolled. Patients developing HCC 6 months after potent NA or before the first LS measurement were excluded. Three hundred and seventy‐one patients were enrolled. The median follow‐up was 5.6 and 3.8 years from potent NA treatment and the first LS measurement respectively. Twenty‐seven patients developed HCC. The 1‐, 3‐, 5‐ and 7‐year cumulated incidences of HCC occurrence were 0%, 2.8%, 5.8% and 9%, respectively. In addition to age > 57 years, LS > =21.5 kPa (HR: 3.86, 95%CI: 1.67‐8.94) was an independent factor associated with HCC occurrence in multivariate analysis. However, the magnitude of change in LS was not associated with HCC development. For the first LS in HCC prediction, the performance was 0.636. There were two to thirteen LS measurements during CVR. The change in LS was classified into four patterns stratified by the first and serial LS. Compared with those with serial LS =21.5 kPa tend to have higher HCC occurrence (P = .062). In summary, LS at CVR was an independent factor associated with HCC development for HBV‐related cirrhosis patients with potent NA. However, LS was not satisfactory in the prediction performance of HCC development.

Background: Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known. Methods: Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up. Results: Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan–Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality. Conclusion: Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently. Keywords: Hepatitis C virus, Hepatocellular carcinoma, Mortality, Recurrence, Antiviral therapy

BackgroundNivolumab and regorafenib are approved second-line therapies for patients with hepatocellular carcinoma (HCC) after sorafenib failure. This study compared the effectiveness of nivolumab and regorafenib following sorafenib.MethodsWe retrospectively enrolled HCC patients who had undergone nivolumab or regorafenib after sorafenib failure. Treatment response, treatment-related adverse events (TRAE) and clinical outcomes of study patients were recorded and analyzed.ResultsA total of 90 patients (male/female: 67/23, mean age: 63 years) were enrolled, including 32 patients in the Nivolumab group and 58 patients in the Regorafenib group. The Nivolumab group had better objective response rates (16% vs 6.4%) and disease control rates (44% vs 31.9%) than the Regorafenib group, but there was no statistical difference. The comparison of time to progression (3.0 months vs 2.6 months, p=0.786) and overall survival (OS) (14 months vs 11 months, p = 0.763) between Nivolumab and Regorafenib groups were also insignificant. Regarding number of TRAE incidences, the Nivolumab group was significantly lower than the Regorafenib group (37.5% vs 68%). After cession of nivolumab/regorafenib, 34 patients (37.8%) (Nivolumab group/Regorafenib group: 11/23) could afford the following therapies. Concerning sequential systemic therapies, 17 patients (18.9%) received third-line therapy, whereas six patients (6.7%) could move to fourth-line therapy. In multivariable analysis, patients who achieved disease control were associated with improved OS (hazard ratio, 0.18; 95% confidence interval, 0.07–0.46; p

Background/aimsA recent study from the United States reported that nearly 12% of hepatocellular carcinomas (HCCs) occurred in patients without cirrhosis. Non-alcoholic fatty liver disease (NAFLD) was the most common liver disease in these patients. We aim to evaluate the characteristics, etiologies, and outcomes of cases of non-cirrhotic HCC in East Asia, where there is a higher prevalence of hepatitis B virus (HBV)-associated non-cirrhotic HCC.MethodsThis retrospective study consecutively enrolled de novo HCC patients managed at our institution from 2011 to 2017. The presence of cirrhosis was assessed by histology; if histology was not available, it was assessed by image study.Results2055 patients with HCC were enrolled in this study. Among them, 529 (25.7%) were non-cirrhotic. The non-cirrhotic patients were younger (60.9 vs. 62.5 years, p = 0.006), included a greater proportion of males (78.1% vs. 71.3%, p = 0.002), and had a lower body mass index (24.3 vs. 25.3 kg/m2, pConclusionsNearly 26% of the HCCs occurred in patients without cirrhosis. HBV was the most common liver disease in these patients, and the survival was better in the non-cirrhotic patients than the cirrhotic patients.

Background and aimsThe Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely applied staging system for hepatocellular carcinoma (HCC) and is recommended for treatment allocation and prognostic prediction. The BCLC guidelines were modified in 2018 to indicate that Child-Pugh A without any ascites is essential for all stages except stage D. This study sought to provide a description of patients with HCC treated at a high-volume liver surgery center in Taiwan where referral is not needed and all treatment modalities are available and reimbursed by the National Health Insurance program. As such, certain variables that could modulate treatment decisions in clinical practice, including financial constraints, the availability of treatment procedures, and the expertise of the hospital, could be excluded. The study further sought to evaluate the adherence to the modified BCLC guidelines.MethodsThis was a retrospective study with prospectively collected data. 1801 consecutive patients with de novo HCC were enrolled through our institution from 2011-2017.ResultsThere were 302 patients with stage 0, 783 with stage A, 242 with stage B, 358 with stage C, and 116 with stage D HCC. Treatment adhering to the modified BCLC guidelines recommendations was provided to 259 (85.8%) stage 0 patients, 606 (77.4%) stage A patients, 120 (49.6%) stage B patients, 93 (26.0%) stage C patients, and 83 (71.6%) stage D patients.ConclusionsWe reported treatment adhering to the modified BCLC guidelines at a high-volume liver surgery center in Taiwan. We found that non-adherence to the modified BCLC staging system was common in treating stage B and C patients.

This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders.

BACKGROUND AND AIMS:The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS:This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS:Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS:We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.

BACKGROUND:Hepatitis C virus core antigen (HCV Ag) assay has been proposed as a more economical alternative to HCV RNA detection. This study aimed to investigate the clinical utility of HCV Ag assay in the monitoring of direct-acting antivirals (DAAs) for chronic hepatitis C patients. METHODS:We analyzed serum samples from 110 patients treated with paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin. The levels for both HCV Ag and HCV RNA assessed by COBAS TaqMan HCV (CTM) Test or Abbott RealTime HCV (ART) assay were evaluated at baseline, week 2, 4, and 12 during treatment and 12 weeks after completion. RESULTS:Baseline HCV Ag levels showed good correlations with HCV viral load (r = 0.879; p

Background & aimsIn 2012, the Barcelona Clinic Liver Cancer (BCLC) system designated a single large hepatocellular carcinoma (SLHCC) (>5 cm) as BCLC stage A rather than stage B. However, a recent study from western countries reported that prognosis following liver resection (LR) among patients with SLHCC was similar to that among patients with BCLC stage B. We aim to evaluate the prognosis following LR among patients with SLHCC from an Asian high-volume liver surgery center.MethodsPatients who underwent curative-intent LR for histologically proven HCC between 2011 and 2017 were enrolled using an HCC registry database. Overall survival (OS) among patients with BCLC stages 0, A, and B was examined. Patients with a SLHCC were classified as BCLC stage A1.ResultsAmong 543 patients, 89 (16.4%) were BCLC stage 0, 289 (53.2%) were BCLC stage A, 92 (16.9%) were BCLC stage A1, and 73 (13.4%) were BCLC stage B. The median follow-up was 38 months. The five-year OS rates among patients with BCLC stages 0, A, A1, and B were 83.5%, 83.7%, 77.4%, and 55.4%, respectively (pConclusionPrognosis following LR among patients with SLHCC was similar to that among patients with BCLC stage A. The prognosis for SLHCC should thus be considered comparable to that for BCLC stage A.

BackgroundIntrahepatic distant recurrence (IDR) is a significant problem for patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The objective of the study was to investigate risk factors and to predict outcomes of recurrent IDR within Milan criteria after complete RFA for primary early-stage HCC.MethodThis retrospective study reviewed 449 patients with intrahepatic distant recurrent HCC after complete RFA for early-stage HCC. After excluding 100 patients who were beyond Milan criteria, with incomplete lab data, or had follow-up less than three months, a total of 349 patient cases were compiled and their baseline characteristics, further treatment modalities after tumor recurrence and survival were analyzed.ResultsAfter a median follow-up of 36.2 months, 92 patients had expired. The majority of patients were male (59.9%) with a median age of 64.3 years (range:38-88). The cumulative 5-year overall survival (OS) rates after treatment for recurrent HCC was 67.2%. On multivariate analysis, end-stage renal disease(Hazard ratio (H.R.) = 2.33, p = 0.021), m-ALBI grade 2a (H.R. = 2.86, p = 0.003) and m-ALBI grades 2b or 3 (H.R. = 2.30, p = 0.009), APRI greater than 1 (H.R. = 1.92, p = 0.036) and 2nd recurrence occurring within 1 year (H.R. = 2.69, pConclusionOur study suggested that presence of end-stage renal disease, m-ALBI grades 2 and 3, APRI >1 and time to 2nd HCC recurrence were all associated with overall survival while the 2nd HCC recurrence was associated with male gender, age ≥65 years, α-fetoprotein level >20 ng/mL, non-surgical therapy, time to IDR, and tumor number> 1.

Hepatitis C virus core antigen (HCV-Ag) immunoassay has been proposed as a more cost and time efficient one-step alternative to the current two-step screening and diagnostic process. This study investigates the correlation between the HCV-Ag immunoassay and the current gold standard of Hepatitis C Virus (HCV) ribonucleic acid (RNA) molecular assay. Stored sera of 221 consecutive treatment-naive patients tested anti-HCV positive were selected to undergo both HCV-Ag immunoassay and HCV RNA molecular assay. Active infection status and HCV genotype were determined using both assays, and correlation was calculated using a logarithmic scale. Among 221 anti-HCV-positive sera, 197 were positive for both HCV Ag (≥3 fmol/L) and HCV RNA (>15 IU/mL), 22 were negative for both tests, while 2 were positive to HCV RNA only. The sensitivity and specificity for HCV Ag in predicting HCV RNA were 99% and 100%, respectively. Out of 199 patients (90%) tested positive for HCV viremia, 107 (56%) were of genotype 1, 77 (38.7%) of genotype 2 and 15 of other genotypes. Analysis of 221 anti-HCV-positive patient sera found a strong positive correlation between HCV RNA and HCV-Ag (r = 0.960, p

In the community screening, those subjects with elevated serum alpha-fetoprotein (AFP) required further abdomen ultrasonography (US) to detect hepatocellular carcinoma (HCC). However, some chronic hepatitis patients might have elevated AFP. AFP-L3, has been proposed to differentiate HCC and hepatitis in elevated AFP cases in Japan for decades, but the utility is limited outside Japan. We conducted this study to elucidate the role of AFP-L3 in the community and the possibility of saving unnecessary US. A total of 56,702 subjects underwent a large-scale healthcare screening in Tainan county in 2004. Among them, 286 residents with AFP more than 20 ng/ml further received US and 169 (59%) had stored baseline sera were enrolled into this study in 2013. Their AFP and AFP-L3 levels were further detected. HCC patients were initially identified through US and personal history. Among 169 studied sera, only 148 (87.6%) samples still had AFP level more than 20 ng/ml after a 10-years frozen period. The decrease of AFP level was significant (481.3 ± 2093.8 ng/ml and 456.1 ± 2095.3 ng/ml in paired-T test, p

Background/Purpose: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients. Methods: We consecutively enrolled 1011 CHC patients who underwent liver biopsy before initiating interferon-based therapy. These patients were followed-up and screened for HCC up to a median of 6.9 years. The influence of rs738409 (GG) genotype on the occurrence of HCC was assessed using the Kaplan–Meier method, then according to the multivariate Cox model. Results: During follow-up, 143 (14.1%) patients developed HCC. rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.634). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.12). Among 261 patients with liver cirrhosis, rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.737). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.72). Conclusion: In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients. Keywords: Patatin-like phospholipase domain containing 3, Hepatocellular carcinoma, Hepatitis C virus

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan produced the management consensus guideline for HCC. Methods: The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention. Results: The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation. Conclusion: With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality. Keywords: Diagnosis, Hepatocellular carcinoma, Staging, Surveillance, Treatment

Background/Purpose: Metabolic risk factors are associated with liver fibrosis. Whether or not metabolic risk factors affect the severity of liver fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or risk factors associated with non-alcoholic fatty liver disease (NAFLD) remains unclear. We aimed to investigate this by transient elastography. Methods: In this cross-sectional study, we enrolled 1513 patients who presented with chronic liver disease (CLD) at a tertiary hospital. Liver stiffness measurement (LSM) >13 kPa was used as a cutoff suggesting possible liver cirrhosis (LC). Results: Possible LC was noted in 7.8% of the CHB patients, 19.9% of the CHC patients, and 11.9% of the patients with risk factors associated with NAFLD. After adjustments for biochemical and virological factors were made, BMI (per 1 kg/m2 increase) (OR: 1.17, 95% CI: 1.06–1.29, P = 0.002) was found to be an independent factor associated with possible LC in CHB patients; BMI (per 1 kg/m2 increase) (OR: 1.15, 95% CI: 1.07–1.24, P

This study aimed to compare the outcomes of combined hepatic resection (HR) plus intraoperative radiofrequency ablation (RFA) and transarterial embolization (TAE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) in case-controlled patient groups using the propensity score. Methods: A total of 179 patients with multifocal HCC treated with HR plus RFA (n = 26) or TAE (n = 153) were retrospectively studied. All patients were classified as BCLC stage B and Child–Pugh class A. Analyses were performed over all participants as well as for propensity score-matched (1:3) patients to adjust for baseline differences. Cumulative overall survival (OS) and time to progression (TTP) were compared between the two groups using the Kaplan–Meier method, and independent predictors were identified by multivariate Cox regression analysis. Results: Patients treated with HR plus RFA had better OS and longer TTP than those with TAE (p = 0.011 and p

This study aimed to evaluate the outcomes of chronic hepatitis B patients with cirrhosis who received long-term nucleos(t)ide analog therapy. Methods: A total of 546 consecutive cirrhotic patients treated with entecavir (n = 359), telbivudine (n = 104), or tenofovir (n = 83) for chronic hepatitis B were enrolled. The incidence of hepatocellular carcinoma (HCC) and overall survival were evaluated. Results: During a median follow-up of 39 months, 56 (10.3%) patients developed HCC and 14 (2.6%) patients died. These outcomes were not associated with different antiviral use. Cox proportional hazard analysis showed that old age (≥60 years) [hazard ratio (HR), 1.74; p = 0.046], statin use (HR, 2.42; p = 0.017), low platelet count (

Abstract This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p

BACKGROUND:Aspartate transaminase-platelet ratio index (APRI) and fibrosis 4 (FIB-4) are two non-invasive indexes to predict liver fibrosis in liver disease. This study was to use APRI and FIB-4 to detect chronic virus hepatitis in community screenings. METHODS:From 2004 to 2013, a series of community-based health screenings for residents aged 40 and older were held in Tainan city. APRI and FIB-4 of each participant were calculated and their association further analyzed with hepatitis status. RESULTS:We enrolled 180359 participants including 18726 (10.4%) hepatitis B virus (HBV), 13428 (7.4%) hepatitis C virus (HCV), 1337 (0.7%) HBV plus HCV and 146868 (81.5%) Non-HBV Non-HCV. The prevalence of chronic HCV increased with the elevation of APRI cut-offs or FIB-4 cut-offs (13.9%, 28.1%, 38.8%, 45.2%, to 49.9% in APRI≥0.3, 0.5, 0.7, 0.9,1.1, p

BACKGROUND & AIMS:Previous studies from western countries have reported that active hepatocellular carcinoma (HCC) was associated with direct-acting antiviral (DAA) treatment failure. We sought to examine this issue in an Asian cohort. METHODS:A retrospective cohort study was conducted on hepatitis C virus (HCV)-infected patients with advanced fibrosis who were treated with DAAs at our hospital between January 2017 and June 2018. RESULTS:We treated 1021 HCV-infected patients during this period. A total of 976 of those patients were enrolled in a per-protocol analysis, including 556 (57.2%) who had genotype 1b infections, and 314 (32.3%) who had genotype 2 infections. The mean age of all 976 patients was 65.5 years, and 44.5% were male. 781 of the patients had no HCC, 172 had inactive HCC, and 23 had active HCC. Non-sustained virologic response (SVR) was noted in 10 (1.3%) patients without HCC, 5 (2.9%) patients with inactive HCC, and 4 (13.0%) patients with active HCC. After adjustment for confounders, active HCC (versus inactive HCC and non-HCC) was associated with non-SVR (adjusted odds ratio [AOR] = 24.5 (95% confidence interval [CI] = 4.4-136.9), P

BackgroundThis study investigated the incidence and predictors of retreatment after discontinuation of either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment in Taiwan.MethodsA total of 535 non-cirrhotic chronic hepatitis B (CHB) patients undergoing either ETV (n = 358) or TDF (n = 177) treatment were enrolled. Patients were followed for at least 12 months after stopping ETV or TDF treatment. Most patients (86.3%) fulfilled the retreatment criteria of Taiwan's National Health Plan.ResultsThe 5-year cumulative rates of clinical relapse and retreatment were 52.1% and 47%, respectively, in 160 hepatitis B e antigen (HBeAg)-positive patients, and were 62% and 54.8%, respectively, in 375 HBeAg-negative patients. The median duration from the end of treatment until clinical relapse and retreatment was 40 and 57 weeks, respectively, for all patients. Multivariate Cox regression analysis revealed that discontinuing TDF treatment, old age, male gender, and higher baseline HBsAg levels were independent factors of retreatment in HBeAg-positive patients; old age, HBV genotype B, and higher baseline and end-of-treatment HBsAg levels were independent factors in HBeAg-negative patients. A total of 18.8% of retreated patients satisfied the retreatment criteria of hepatic decompensation according to Taiwan's National Health Plan. Of the 64 patients who had clinical relapse without retreatment, 17 achieved sustained virological remission and 26 did not experience clinical relapse until their last visit after clinical relapse. Four patients developed HBsAg loss.ConclusionsThe 5-year retreatment rate was about 50% in HBeAg-positive and HBeAg-negative patients. Discontinuing TDF treatment was an independent factor of retreatment in HBeAg-positive patients.

Background and aimPrevious studies have reported that sustained virological response (SVR) to interferon-based treatment reduces the risk of mortality in chronic hepatitis C (CHC) patients, mainly in cirrhotic patients. A population-based study reported that metabolic risk factors increase the risk of mortality in CHC patients. We aim to investigate the association between SVR, metabolic risk factors and mortality in CHC patients with and without advanced fibrosis.MethodsWe collected data from 1452 CHC patients who underwent interferon-based therapy. All patients underwent liver biopsy prior to therapy. Mild fibrosis was defined as a modified Knodell score of 0-2, while advanced fibrosis was defined as a score of 3-4.Results1452 patients were followed up for a median (IQR) of 6.6 (4.2-9.4) years, 1124 patients (77.4%) achieved SVR, 619 patients (42.6%) were advanced fibrosis. 14 patients with mild fibrosis and 55 patients with advanced fibrosis died during follow-up period. According to multivariate Cox regression analyses, SVR reduced the risks of all-cause mortality (HR, 0.21; 95% CI, 0.12-0.37; PConclusionSVR and metabolic risk factors are associated with mortality in CHC patients given interferon-based treatment.

Background and aimTransient elastography and fibrosis-4 index (FIB-4) have been proposed to access hepatic fibrosis and steatosis for patients with chronic liver disease. This study was to determine the changes of liver stiffness (LS), controlled attenuation parameter (CAP) value and FIB-4 and their associated factors for chronic hepatitis C (CHC) patients who underwent direct-acting antivirals (DAAs).Patients and methodsConsecutive patients with CHC in advanced fibrosis or compensated cirrhosis undergoing paritaprevir/ritonavir/ombitasvir plus dasabuvir therapy and with LS and CAP before and 12 weeks after treatment were enrolled. The demographics, clinical characteristics and treatment outcomes were reviewed. The changes of LS, FIB-4, CAP and their associated factors were analyzed.ResultsA total of 213 patients (mean age: 63.7 years) with complete recommended treatment were enrolled. All patients achieved sustained virological response at 12 weeks (SVR12) of follow-up. The mean values of LS, CAP and FIB-4 index before treatment were 18.5kPa, 283dB/m and 5.05 respectively. While there was no significant change in CAP, LS and FIB-4 decreased significantly at the time of SVR12 (pConclusionFor CHC patients in advanced fibrosis or compensated cirrhosis, DAAs improved LS and FIB-4 index at SVR12. Higher baseline LS and FIB-4 contributed to greater reductions. However, there was no significant change in CAP value.

While new direct-acting antiviral therapies for hepatitis C virus (HCV) are the standard of care, interferon-α (IFN-α) remains a standard therapy in Taiwan based on its low cost and high response rate to IFN-α-based therapy. IFN-α exerts antiviral activity by inducing the expression of hundreds of genes that establish an antiviral state via Jak kinase (JAK)/signal transducers and activators of transcription (STAT) signaling. We quantified the transcript levels of JAK/STAT signaling genes in peripheral blood mononuclear cells of HCV genotype 1 patients and estimated the correlation between transcript levels and patient responses to IFN-α-based therapy. Methods: A total of 100 HCV genotype 1 naïve patients were enrolled. All patients received response-guided therapy for 24–48 weeks with pegylated IFN-α and ribavirin. Peripheral blood mononuclear cells were collected before treatment. Twenty patients with sustained virological responses (SVR) and 20 patients without SVR were selected for a JAK/STAT signaling genes transcript analysis using multiplex reverse transcription-polymerase chain reaction. Transcripts that were upregulated or downregulated were further validated in 100 patients. Results: Suppressor of cytokine signaling 1 (SOCS1) expression was upregulated in SVR patients compared with non-SVR patients (relative quantification = 2.14) based on a multiplex reverse transcription-polymerase chain reaction analysis. We further analyzed SOCS1 expression in 100 patients. We found that SOCS1 expression did not differ significantly between SVR and non-SVR patients. Conclusion: Peripheral blood SOCS1 expression before treatment was not associated with SVR in HCV genotype 1 patients treated with pegylated IFN-α and ribavirin.

Recent studies have shown that serum vitamin D deficiency is a negative predictor of response to peginterferon plus ribavirin therapy for Caucasian patients with chronic hepatitis C (CHC). Whether vitamin D receptor (VDR) gene polymorphisms associate with antiviral response in Asian CHC patients remains unclear. Methods: We recruited 139 Asian patients with CHC genotype-1 who achieved 80/80/80 adherence of response-guided peginterferon plus ribavirin therapy. BsmI rs1544410, ApaI rs7975232, and TaqI rs731236 were genotyped and related to clinical and virological features and to treatment outcome. Results: Patients carrying bAt [CCA] haplotype (p=0.033), ApaI CC genotype (p = 0.033), and TaqI AA genotype (p = 0.037) had a higher HCV load as compared to those with other haplotypes, ApaI CA/AA genotype and TaqI AG genotype, respectively. A sustained virological response (SVR) was achieved in 74 (53%) of the patients. Polymorphisms in VDR gene did not correlate with rapid virological response and SVR achievement. Stepwise logistic regression analysis showed that rs12979860 CC type [odds ratio (OR): 5.56, p=0.007], platelet counts ≥ 15 × 1010/L (OR: 4.80, p=0.001), and rapid virological response achievement (OR: 8.36, p

BACKGROUND AND AIM:The aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are commonly used compound surrogates for advanced fibrosis in chronic hepatitis C (CHC) patients. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. We sought to investigate the optimal cutoff values of the two compound surrogates for predicting cirrhosis stratified by AST level. METHODS:This retrospective study enrolled 1716 treatment-naive CHC patients who underwent liver biopsy prior to interferon therapy from 1997-2010. Fibrosis was scored according to the modified Knodell classification. The upper limit for normal AST in our hospital is 37 IU/L. We stratified the enrolled patients into the categories of AST≤37 IU/L (N = 132), 37148 IU/L (N = 346). RESULTS:436 patients had cirrhosis (F4). The area under receiver operating characteristic (AUROC) analysis results distinguishing cirrhosis (F4) from non-cirrhosis (F0-F3) were 0.81 for APRI and 0.85 for FIB-4 in patients with AST≤37 IU/L; 0.71 for APRI and 0.72 for FIB-4 in patients with 37148 IU/L. The optimal cutoff values of APRI and FIB-4 for the diagnosis of cirrhosis were 0.6 and 1.4, respectively, in patients with AST≤37 IU/L; 1.1 and 2.2, respectively, in patients with 37148 IU/L. CONCLUSIONS:We provide optimal cutoff values of both APRI and FIB-4 to predict cirrhosis stratified by AST levels, which should be more feasible compared with the single cutoff values proposed in previous studies.

Whether serum proteome changes can predict treatment response in chronic hepatitis C remains unclear. We investigated the association between serum proteome changes and virological responses in chronic hepatitis C virus genotype 1b (HCV-1b) patients treated with pegylated interferon (PegIFN) plus ribavirin (RBV). Methods: One hundred and thirty-six HCV-1b patients who had completed a course of PegIFN plus RBV for 24 weeks, had a 24-week follow-up, and had pretreatment serum available were enrolled. These patients were divided into training and validation groups. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF/MS) for peptide profiling and ClinPro Tools version 2.0 bioinformatics software for data analysis. Results: Seventy-four patients (54%) had a sustained virological response (SVR), whereas 62 did not. We identified three protein peaks in pretreatment sera where the expression levels significantly differed between SVR and non-SVR (p