Search

Abstract Lifestyle modification is the standard of care for nonalcoholic fatty liver disease (NAFLD) patients. We aimed to investigate the efficacy of a short‐term lifestyle modification program in the disease course of Taiwanese nonalcoholic steatohepatitis (NASH) patients with paired biopsies. All patients received a 6‐month, strict multidisciplinary program of lifestyle modifications led by physicians, dieticians, and nursing staff. The histopathological and clinical features were assessed. The endpoints were normalization of transaminase levels, metabolic parameters, a decrease in the NAFLD activity score (NAS) ≥1, and a decrease in the fibrosis stage ≥1. We also aimed to elucidate the predictors associated with disease progression. A total of 37 patients with biopsy‐proven NASH were enrolled. The normalization of transaminase levels increased from 0% to 13.5%. There were also significantly increased proportions of patients with normal total cholesterol, triglyceride, and hemoglobin A1c levels. Fifteen (40.5%) patients had an increased NAS ≥1, whereas 10 (27.0%) patients had NAS regression. Twelve (32.4%) patients had increased fibrosis ≥1 stage. Only 2 (5.4%) patients experienced fibrosis regression. A high fasting plasma glucose (FPG) level was associated with NAS progression. Older age and higher transaminase and FPG levels were factors associated with fibrosis progression. Seven (18.9%) patients achieved a body weight reduction >3%, and 4 (57.1%) of them experienced NAS regression. No significant effect of weight reduction on the progression of fibrosis was observed. The short‐term lifestyle modification program significantly decreased liver enzymes and metabolic parameters in NASH patients. A more precise or intensive program may be needed for fibrosis improvement.

Abstract The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p

Abstract The accuracy of noninvasive seromarkers in predicting liver fibrosis in metabolic dysfunction‐associated fatty liver disease (MAFLD) patients with or without viral hepatitis is elusive. The AST to platelet ratio index (APRI), fibrosis‐4 index (FIB‐4), and NAFLD fibrosis score (NFS) were assessed in 871 MAFLD patients who received elastography in a viral hepatitis‐endemic area. The area under the receiver operating characteristic (AUROC) curve increased substantially with increasing fibrotic stage across the three biomarkers. APRI (AUROC range 0.73–0.80) and FIB‐4 (AUROC range 0.66–0.82) performed better than NFS (AUROC range 0.63–0.75). When patients were divided into viral and non‐viral MAFLD groups, a better AUROC of APRI (range 0.76–0.80) and FIB‐4 (range 0.68–0.78) than NFS (range 0.62–70) existed only in viral MALFD but not in non‐viral MAFLD. Regarding the NFS, the AUROC was higher in non‐viral MAFLD (range 0.69–0.86) and outperformed viral MAFLD at all fibrotic stages. The accuracy in predicting liver fibrosis increased with the advancement of liver disease for the three biomarkers. NFS exerted better diagnostic accuracy in non‐viral than in viral MAFLD patients across different fibrotic stages. The best accuracy was 91.1% using the cutoff value of −9.98 for the NFS in predicting liver cirrhosis in non‐viral MAFLD patients. The APRI and FIB‐4 performed better than the NFS in predicting liver fibrosis in MAFLD as a whole. The suboptimal performance and accuracy of the NFS existed only in viral MAFLD patients. Caution should be taken when assessing the NFS in MAFLD patients with viral hepatitis.

Abstract We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti‐HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5], nitrogen dioxide [NO2], ozone [O3] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05–4.77; p

Abstract Elevated serum gamma‐glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)‐related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month‐6) after initiating NAs were measured to explore their association with all‐cause, liver‐related, and non‐liver‐related mortality. The annual incidence of all‐cause mortality was 0.9/100 person‐years over a follow‐up period of 17,436.3 person‐years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month‐6‐GGT levels (62.1 vs. 38.4 U/L, p 75 percentile of pretreatment GGT levels was observed with respect to the all‐cause mortality (trend p

Abstract Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti‐HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post‐treatment follow‐up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy‐three (4.9%) individuals were seropositive for anti‐HCV antibodies. Of the 73 anti‐HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty‐three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post‐treatment follow‐up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient‐centered and integrated outreach program facilitated HCV care in this marginalized population.

Abstract Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV‐related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV‐related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety‐one (23%) of the HBV‐aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

Abstract Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2‐h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty‐three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3 months after the end‐of‐treatment) by DAAs were consecutively enrolled. Pre‐ and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n = 77), 18.6% (n = 99), and 67.0% (n = 357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p = 0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5 mg/dl, p

Abstract Chronic hepatitis B (CHB) patients with low disease activity are at risk of liver fibrosis. The age‐adjusted fibrosis‐4 index (FIB4‐AA), developed in our previous publication, and was implemented to evaluate the tendency of liver fibrosis in these patients. We aimed to investigate the rate of liver fibrosis in CHB patients with low disease activity. Resuming our previous study, the FIB‐4 changes of 244 antiviral treatment‐naïve CHB patients, with a total of 1243.48 person‐years, were reviewed. Among the cohort, patients were categorized as FIB4‐AA positive or negative according to the results of their last FIB4‐AA minus their initial FIB‐4 during at least 18 months of observation time. The compound annual growth rate (CAGR) of FIB‐4 was calculated for the FIB4‐AA positive and negative groups. The assumed healthy controls had an FIB‐4 CAGR calculated to be 2.34% for both men and women, while the FIB‐4 CAGR of the whole study cohort was 2.84% ± 6.01%. FIB4‐AA positive effectively identifies CHB patients with higher mean FIB‐4 CAGR (7.11% ± 3.88% vs. −2.36% ± 3.52%, p

Abstract Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link‐to‐care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire‐based interviews for HCV. The rates of disease awareness, accessibility, and anti‐HCV therapy were evaluated in anti‐HCV‐seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti‐HCV seropositive. Of these 1789 anti‐HCV‐seropositive participants, data of 594 participants from questionnaire‐based interviews in 2005–2018 were analyzed for HCV care cascades. Overall, 24.9% of anti‐HCV‐seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB‐4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link‐to‐care, and treatment uptake in the HCV care cascade in an HCV‐hyperendemic area, even in the initial era of direct‐acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination.

Abstract The role of Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) in the prediction of disease severity in nonalcoholic fatty liver disease (NAFLD) remains elusive. This study evaluated the performance of WFA+‐M2BP in predicting fibrosis in patients with NAFLD. A total of 80 patients with biopsy‐proven nonalcoholic steatohepatitis (NASH) were enrolled. Serum WFA+‐M2BP levels were measured using standard methods. The fibrosis‐4 (FIB‐4) index was also measured. The mean values of WFA+‐M2BP were 1.0, 1.0, 0.8, and 2.2 in Metavir fibrosis stage F0, F1, F2, and F3‐4, respectively (linear trend p = 0.005). The optimal cut‐off value of WFA+‐M2BP in predicting advanced fibrosis (F3‐4) was 1.37 cut‐off index (COI), yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of 75.0, 79.4, 39.1, 94.7, and 78.7%, respectively (p

Abstract Cancer stem cell is considered as an important cause to exacerbate the prognosis. NANOG and POU5F1 are markers for cancer stem cells. The associations between NANOG and POU5F1 expressions with the sorafenib anticancer effects in primary cultured hepatocellular carcinoma (HCC) cells were investigated. Eight primary cultured HCC parent cell lines and 13 subgroups established by flow cytometric sorting using NANOG and POU5F1 as targets were investigated with clinically achievable sorafenib plasma concentrations (5 and 10 μg/mL). Sorafenib showed obvious downregulation of RAF/MEK/ERK signaling pathways and dose‐dependent anti‐proliferative effects only on s003 parent cell line, which showed the lowest expression of NANOG among all tested cell lines except one downregulated NANOG with upregulated POU5F1 s020 subgroup. Sorafenib also inhibited proliferation in this s020 subgroup but promoted proliferation in its parent cell line. For the only one downregulated NANOG alone s015 subgroup, sorafenib which had no influence on its parent cell line inhibited proliferation in this subgroup. Only the above three cell lines could demonstrate sorafenib antiproliferative effects. On the contrary, sorafenib promoted proliferation in three (s003, s015, s071) out of four upregulated NANOG alone subgroups. On the other hand, Sorafenib showed diverse influence on proliferation among four upregulated POU5F1 alone subgroups. In conclusion, NANOG rather than POU5F1 expression is a critical marker for the anticancer effects of sorafenib on HCC. The sorafenib anticancer effects on HCC cells with high NANOG expression were limited. Sorafenib should be combined with other drug able to target cancer cells with high NANOG expression.

Abstract Previous in vitro and in vivo experiments had demonstrated dose‐dependent anti‐cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar‐plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost‐effectiveness consideration.

Abstract Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long‐term outcomes. Several direct‐acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non‐SOF‐based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype‐2 (GT‐2) patients in Taiwan. However, there is limited real‐world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real‐world efficacy in CHC GT‐2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT‐2 patients who were treated with SOF‐based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non‐SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT‐2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Abstract Whether patients with advanced hepatocellular carcinoma (aHCC) benefit from hepatitis C virus (HCV) eradication is uncertain. We aimed to investigate whether a survival benefit was conferred by HCV eradication in aHCC patients. This retrospective cohort study enrolled 168 HCV‐infected aHCC patients from April 2013 to January 2019. All patients were treated with sorafenib. Endpoints included overall survival (OS), progression free survival (PFS), and time to liver decompensation. Patients with undetectable HCV RNA exhibited reduced aspartate aminotransferase and alpha fetoprotein levels, as well as an attenuated proportion of aHCC at initial diagnosis but increased albumin and mean sorafenib daily dosing. Patients with undetectable HCV RNA exhibited significantly longer OS compared to patients with detectable or unknown HCV RNA, which was an independent factor of OS (HR: 0.56, 95% CI: 0.350‐0.903, P = .017). Patients with undetectable HCV RNA also presented a trend for longer PFS (HR 0.68, 95% CI: 0.46‐1.00, P = .053). The survival benefit was considered with respect to the significantly prolonged time to Child‐Pugh B scores in patients with undetectable HCV RNA (HR 0.59, 95% CI: 0.38‐0.92, P = .020). Patients with detectable HCV RNA at sorafenib initiation who further received direct acting antiviral therapy also had significantly longer OS (HR 0.11, 95% CI: 0.02‐0.81, P = .030) and PFS (HR 0.23, 95% CI: 0.06‐0.99, P = .048). In conclusion, abolishing HCV viremia preserves liver function and confers a survival benefit in advanced HCC patients on sorafenib treatment.

Abstract Hepatitis C virus (HCV) eradication deteriorates lipid profiles. Although HCV eradication may reduce the risk of vascular events as a whole, whether deteriorated lipid profiles increases the risk of cardio‐cerebral disease in certain patients is elusive. Serial lipid profiles were measured before, during, at and 3 months after the end of direct‐acting antivirals (DAAs) therapy, and annually thereafter in chronic hepatitis C patients who achieved a sustained virological response (SVR, undetectable HCV RNA at posttreatment week 12). The primary end‐point was the occurrence of the events. A total of 617 patients were included, with a mean follow‐up period of 26.8 months (range: 1‐65 months). The total cholesterol and low‐density lipoprotein cholesterol (LDL‐C) levels increased significantly from treatment week 4 to 2 years after treatment. Logistic regression analysis revealed that the factors independently associated with a significant cholesterol increase included age (odds ratio [OR]/95% confidence intervals [CIs]:1.02/1.006‐1.039, P = .007) and smoking (OR/CI:3.21/1.14‐9.02, P = .027). Five patients developed cardio‐cerebral diseases during 1376 person‐years follow‐up period. Compared to patients without vascular events, a significantly higher proportion of those with vascular events experienced an LDL‐C surge >40% (80% vs 19.9%, P = .001). Cox‐regression analysis revealed that an LDL‐C surge >40% was the only factor predictive of vascular events (HR/CI: 15.44/1.73‐138.20, P = .014). Dyslipidemia occurred after HCV eradication, and it was associated with the risk of cardio‐cerebrovascular diseases. Attention should also be paid to the extrahepatic consequence beyond liver‐related complications in the post‐SVR era.

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.

Abstract Sorafenib is currently the first‐line therapy for advanced hepatocellular carcinoma (aHCC) patients. However, the outcomes and prognostic factors of sorafenib therapy have not been well investigated. We aimed to investigate the pretreatment factors and outcomes among Taiwanese aHCC patients receiving sorafenib treatment. A total of 347 patients with aHCC and well‐compensated liver cirrhosis (Child‐Pugh A) status receiving sorafenib were consecutively enrolled from March 2013 through December 2016. Pre‐treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. The factors associated with overall survival were also investigated. The median overall survival of all the patients was 238 days (range, 9‐1504 days) with a 1‐year overall survival of 43.2%. Positive hepatitis B surface antigen and absence of portal vein thrombosis (PVT) were independent factors associated with better overall survival. The median duration of sorafenib therapy was 93.0 days (range, 4‐1504 days). After stopping sorafenib, the median survival was 93.0 days (range, 1‐1254 days). The 1‐year survival after stopping sorafenib was 21.2%. In chronic hepatitis B patients, total bilirubin level was the only factor associated with overall survival. Hepatitis C antibody RNA negativity, tumor size, PVT, and white blood cell count were the independent factors associated with survival among those chronic hepatitis C patients. There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients.

Abstract The majority of patients undergoing methadone maintenance treatment (MMT) are neither examined nor treated for hepatitis C virus (HCV) infection. We aimed to evaluate an integrated referral model in the management of HCV among MMT patients. This retrospective study included 390 HCV‐infected MMT patients between April 2015 and May 2017. Patients who tested positive for HCV antibodies were referred to a liver clinic by MMT case managers or psychiatrists. Patients who agreed to receive anti‐HCV treatment were treated with pegylated interferon and ribavirin. The rate of patient engagement at a liver clinic increased from 14.1% to 58.2% after integrated care. Multiple logistic regression analysis showed that higher education level (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.01‐2.60) and elevated ALT level (OR, 4.30; 95% CI, 2.70‐6.85) were independently associated with patients who accepted referral. Active drug use (OR, 0.52; 95% CI, 0.31‐0.85) was inversely associated with referral acceptance. Of the 112 patients who met the criteria for anti‐HCV therapy, 66 (58.9%) were treated with pegylated interferon and ribavirin. Finally, the rate of treatment completion and sustained virological response (SVR) was 65.2% and 54.5%, respectively, among the 66 patients. Treatment completion (OR, 39.67; 95% CI, 7.80‐201.62) was found to be the only independent factor associated with SVR achievement. Although integrated care by psychiatrists and hepatologists significantly increased the rates of engagement and acceptance of antiviral treatment for HCV‐infected MMT patients, only a minority of MMT patients achieved successful treatment.

Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta-cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype-1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta-cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta-cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR.

Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) has recently been developed as a promising liver fibrosis glyco biomarker. We assessed its efficacy in evaluating liver disease severity in chronic hepatitis C (CHC) in Taiwan. The association between WFA+-M2BP and histological features was evaluated among those CHC patients underwent liver biopsy. We also aimed to clarify the factors determining the performance of WFA+-M2BP in CHC. A total of 229 CHC patients were consecutively recruited. The mean value of WFA+-M2BP in patients from F0 to F4 was 1.68, 2.23, 3.45, 3.48, 3.77 respectively (linear trend P = 0.008). Linear regression analysis revealed that alanine aminotransferase (odds ratio [OR]: 0.03, 95% confidence intervals [CI]: 0.02–0.05, P

Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 μg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24–48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.

Treatments with pegylated interferon/ribavirin (PEG-IFN/RBV) has been standard-of-care in patients with chronic hepatitis C virus (HCV) (CHC) infection and reimbursed in Taiwan. However, the actual cost-effectiveness remains unclear. We aimed to evaluate a real-world cost-effectiveness for CHC patients treated with PEG-IFN/RBV by using a clinical cohort with linkage to the National Health Insurance Research Database of Taiwan. The total and itemized medical-care expenses of outpatient visits of 117 treatment-naïve CHC patients with linkage to the two million sampling of the National Health Insurance Research Database were collected. Four components of costs were assessed, including antiviral agents, nonantiviral agents, laboratory testing and consultation costs. The cost per sustained virological response (SVR) achieved was calculated to evaluate the cost-effectiveness. The average cost per treatment in 117 naïve Taiwanese CHC patients was $4620. With an overall SVR rate of 78.6%, the average cost per SVR was $5878. The average medical-care cost per treatment for 52 Genotype 1 (G1) patients was $5133, including $4420 for antivirals, $380 for nonantivirals, $302 for laboratory, and $78 for consultation, compared to $4209, $3635, $317, $233, and $56 for 65 Genotype 2 (G2) patients. With an SVR rate at 67.3% for G1 and 87.7% for G2 patients, the cost per SVR achieved was significantly higher in G1 patients than those in G2 patients ($7627 vs. $4799, p = 0.001). In the current study, we provided the real-world cost-effectiveness of PEG-IFN/RBV for treatment-naïve CHC patients. The genotype-specific cost-effectiveness could enhance decision-making for policy-makers in the coming era of directly acting antiviral therapy.

The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p

In Taiwan, injecting drug use has been the main route of human immunodeficiency virus (HIV) transmission since 2005, with hepatitis B virus (HBV) and hepatitis D virus (HDV) also having similar transmission routes. This has now become an important public health issue. The aim of this study is to explore the conditions of HDV infections between injecting drug users (IDUs) with and without HIV infection in Southern Taiwan. In this study, 87 IDUs were enrolled, including 27 anti-HDV seronegative IDUs and 60 anti-HDV seropositive IDUs, and the results of their liver function tests, CD4 cell counts, and anti-HIV and HIV RNA levels were analyzed. The prevalence of anti-HDV seropositivity among hepatitis B surface antigen (HBsAg) seropositive IDUs in this study was 68.9% (60/87). The prevalence rate of anti-HDV seropositive IDUs among anti-HIV seronegative and anti-HIV seropositive cases was 40.0% (12/30) and 84.2% (48/57), respectively. Anti-HIV seropositivity was related to anti-HDV seropositivity (odds ratio = 9.34, 95% confidence interval = 2.67–31.59, p

Sonography-based noninvasive liver fibrosis assessment is promising in the prediction of treatment efficacy and prognosis in chronic liver disease (CLD) patients. Acoustic radiation force impulse imaging (ARFI) is a newly-developed transient elastography (TE) method integrated into a conventional ultrasound machine. The study aimed to assess the performance of ARFI imaging in the diagnosis of liver fibrosis in Taiwanese CLD patients. We also aimed to search for the optimal cut-off values in different fibrosis stages. A total of 60 CLD patients (40 males; mean age, 51.8±11 years) were consecutively included. They received standard ARFI measurement within 2 weeks at the time of liver biopsy. There were eight patients with Metavir fibrosis stage 0 (F0), 16 patients with F1, 20 patients with F2, eight patients with F3, and eight patients with F4, respectively. The mean values among patient with F0, F1, F2, F3, and F4 were 1.17±0.13, 1.30±0.17, 1.31±0.24, 2.01±0.45, and 2.69±0.91, respectively (p

In Taiwan, the number of new cases of human immunodeficiency virus (HIV) infection via drug injection has been increasing since 2003. Due to HIV and hepatitis B virus (HBV) having similar transmission routes, HBV and HIV infections among injecting drug users (IDUs) has become an important public health issue. The aim of this study was explore the prevalence of HBV infection among IDUs with and without HIV infection, and examine whether HIV infection is associated with HBV infection among IDUs in Southern Taiwan. We enrolled 566 IDUs, including 87 anti-HBV positive IDUs and 479 anti-HBV negative IDUs, and also analyzed the results of liver function tests, HBV DNA, anti-HIV, HIV RNA, and CD4 cell count. The results showed that the prevalence of HBV infection among IDUs was 15.4%. The prevalence of hepatitis B surface antigen (HBsAg) was higher among individuals born before 1985 (15.9% vs. 4.0%), but this was not significant. Anti-HIV seropositivity was related to HBsAg seropositivity [odds ratio (OR) = 2.47, 95% confidence interval = 1.26–4.82, p = 0.008). Anti-HCV and anti-HIV were risk factors for abnormal alanine aminotransferase (ALT; OR = 2.11, 95% confidence interval = 1.005–4.42, p = 0.048 and OR = 1.47, 95% confidence interval = 1.02–2.10, p = 0.04, respectively), and HBsAg was not a factor related to abnormal ALT. In conclusion, the prevalence of HBV infection was similar in the general population and in IDUs, and due to anti-HIV seropositivity being significantly related to HBsAg seropositivity, HBV infection among IDUs is still important. We suggest that for IDUs, HBsAg should be monitored closely.

The prevalence and characteristics of patients with hepatitis C virus mixed genotype 1 and 2 infection (HCV-1/2) remains unclear. For each HCV-1/2 patient with histological data available, two age- and sex-matched HCV-1 and HCV-2 infected patients were selected for comparison, respectively. Of the 2776 patients, 261 (9.4%) patients were identified as having mixed HCV-1/2 infection. The histological severity did not differ among HCV-1/2 patients and controls. The proportion of patients with the interleukin-28B (IL-28B) rs8099917 TT genotype did not differ between patients with mixed-1/2 and HCV-1 infection (82.6% vs. 86.5%, p = 0.38). However, HCV-2 infected patients had a significantly higher proportion of the rs8099917 TT genotype compared to patients with mixed HCV-1/2 infections (91.6% vs. 82.6%, p = 0.03). The HCV RNA levels were similar in patients with HCV-1/2 and HCV-1 infections (5.5 ± 0.8 log IU/mL vs. 5.5 ± 0.9 log IU/L, p = 0.73), which were both significantly higher than that of HCV-2 infection (5.1 ± 0.9 log IU/mL, both p

The role of transcatheter arterial chemoembolization (TACE) prior to curative therapy is still unclear. The aim of our study was to elucidate the survival of single hepatocellular carcinoma (HCC) and also to clarify whether TACE plus sequential curative therapy provides benefits in single HCC. A total of 470 patients with a diagnosis of single HCC between 2005 and 2010 were studied. The factors associated with clinical outcomes were analyzed. The outcomes between patients who underwent neoadjuvant TACE and those who did not were also compared. The 1-, 3-, and 5-year overall survival (OS) rates of all patients were 92.6%, 73.3%, and 59.6%, respectively. Child-Pugh class A [HR: 2.04, 95% confidence interval (CI): 1.277–3.254, p = 0.003], very early stage Barcelona Clinic Liver Cancer (BCLC) (HR: 2.03, 95% CI: 1.021–4.025, p = 0.043), tumor size

Hepatitis B virus surface antigen (HBsAg) levels reflect disease status and can predict the clinical response to antiviral treatment; however, the emergence of HBsAg mutant strains has become a challenge. The Abbott HBsAg quantification assay provides enhanced detection of HBsAg and HBsAg mutants. We aimed to evaluate the performance of the Abbott HBsAg quantification assay with automatic sample dilutions (shortened as automatic Architect assay), compared with the Abbott HBsAg quantification assay with manual sample dilutions (shortened as manual Architect assay) and the Roche HBsAg quantification assay with automatic sample dilutions (shortened as Elecsys). A total of 130 sera samples obtained from 87 hepatitis B virus (HBV)-infected patients were collected to assess the correlation between the automatic and manual Architect assays. Among the 87 patients, 41 provided 42 sera samples to confirm the linearity and reproducibility of the automatic Architect assay, and find out the correlation among the Elecsys and two Architect assays. The coefficients of variation (0.44–9.53%) and R2 = 0.996–1, which were both determined using values obtained from the automatic Architect assay, showed good reproducibility and linearity. Results of the two Architect assays demonstrated a feasible correlation (n = 130 samples; R = 0.898, p 0.93 in all cases). In conclusion, the correlation between the automatic and manual dilution Architect assays was feasible, particularly in the HBeAg-negative and low DNA groups. With lower labor costs and less human error than the manual version, the Abbott automatic dilution Architect assay provided a good clinical performance with regard to the HBsAg levels.

Gallbladder (GB) stones have been associated with several metabolic factors and liver diseases. This community-based study aimed at investigating the prevalence rate of GB stones and its associated factors in a hepatitis B virus (HBV)/hepatitis C virus (HCV)-endemic township in southern Taiwan. A total of 1701 residents (689 males and 1012 females; mean age: 51.2 ± 16.0 years) were enrolled in this prospectively designed screening project. Serum biochemistry tests, including testing for levels of serum aspartate aminotransferase, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and antibody to HCV (anti-HCV) were conducted. In addition, a hepatobiliary ultrasonographic (US) examination was also conducted. Of the 1701 residents, 243 (14.3%) and 475 (27.9%) were found to be positive for HBsAg and anti-HCV, respectively. Results of the US examination revealed the prevalence rate of GB stone and fatty liver to be 6.8% and 55.6%, respectively. Using univariate analyses we found that significantly higher proportions of the participants with GB stone were male, over 50 years of age, positive for anti-HCV (p = 0.001, p 50 year) were identified as independent factors associated with the formation of GB stones. Anti-HCV was associated with GB stones in males but not in females in both univariate and multivariate analyses. GB stones were found to have a prevalence rate of 6.8% in this HCV/HBV hyperendemic township and are associated with higher mean age. A correlation between chronic hepatitis C and GB stones is observed only among males.

Hepatitis B and hepatitis C are highly prevalent in Taiwan. Chronic hepatitis patients are at high risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). However, HCC in association with liver abscess is very rare. Accordingly, this study analyzed the characteristics of HCC patients with liver abscess to improve the differential diagnosis of this condition. From January 2005 to July 2007, the medical records of nine HCC patients (4 females, 5 males; mean age, 65.8 years) treated for abscess formation at Kaohsiung Medical University Hospital were retrospectively reviewed. Their clinical characteristics, images, management approaches and outcomes were analyzed. Fever and highly elevated alkaline phosphatase levels were noted in all patients. All aspirate cultures revealed Klebsiella pneumoniae. All of the cases of HCC were confirmed by cytology or pathology. The imaging studies, which included abdominal ultrasonography and computed tomography, revealed liver tumors in all patients. In some cases, lead-enhanced hypervascular areas were noted. The patients were treated with antibiotic therapy, transhepatic arterial chemoembolization, or surgery. The findings of this study indicate that focal liver inflammatory changes may mimic solid neoplasms. Differential diagnosis of HCC with abscess is extremely difficult and may require aspiration cytology or pathology.

Metabolic syndrome (MS) is a complicated disorder associated with a high risk of future development of micro- and macrovascular complications. The extrahepatic manifestations of hepatitis C virus (HCV) infection can include multiple metabolic abnormalities. However, the extent, severity, and characteristics of MS in HCV-infected patients have rarely been investigated in community-based settings. This study aimed to determine the difference in prevalence and distribution of the components of MS between HCV-infected patients and healthy controls. Multipurpose mass screening of adults was conducted in an HCV-endemic area of Southern Taiwan. Clinical profiles in terms of anthropometric data and MS components, as well as viral hepatitis markers, were assessed. Two hundred and thirty-seven adults (94 males; mean age, 55.5 ± 10.8 years) were recruited. The prevalence of anti-HCV seropositivity was 39.2% (93/237). The prevalence of MS was higher in the HCV-infected individuals (24.7%, 23/93) than in the control, uninfected subjects (13.2%, 19/144, p = 0.02). In terms of MS components, HCV-infected subjects had a higher prevalence of high waist circumference (51.6% vs. 25.7%, p < 0.001) and hypertension (58.1% vs. 36.8%, p = 0.001) than controls. Multivariate logistic regression analysis demonstrated that anti-HCV positivity was significantly associated with MS (odds ratio, 6.4; 95% confidence interval, 1.82–22.84; p = 0.004). HCV infection was associated with a higher prevalence of MS. Determination of MS in patients with HCV infection could therefore be indicated.

Diagnosis of abdominal splenosis is often undiagnosed until treatment for splenic rupture or splenectomy. This report describes a patient with splenosis mimicking hepatic tumor. The patient had a history of splenic trauma with splenectomy and chronic hepatitis C. After routine abdominal ultrasound revealed a liver nodule, further imaging studies, including magnetic resonance imaging, computed tomography and angiography, were performed. After the patient eventually underwent surgery, pathology revealed splenic tissue. Despite its distinguishable clinical features, splenosis is difficult to identify by modern imaging modalities. Therefore, accurate and timely diagnosis of this disease requires constant vigilance.