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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 FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

Aim 25-Hydroxy vitamin D (Vit D) plays a role in treatment outcomes in chronic hepatitis C virus (HCV) infection. We aimed to clarify whether HCV replication is inhibited by Vit D in HCV replicon cells. Clinical implication was assessed for rapid virological response (RVR) and sustained virological response (SVR) among those patients receiving antiviral therapy. Methods Cell survival and viral loads were observed in Con1 (genotype 1b) and J6/JFH (genotype 2a) cells treated with different doses of Vit D. Three groups of patients with different treatment responses were recruited to assess their Vit D levels: group A, RVR−/SVR−; group B, RVR+/SVR−; and group C, RVR+/SVR+. Results The viral load of Con1 cells decreased by 69%, 80%, and 86% following treatment with 1 μM, 5 μM, and 10 μM Vit D, respectively ( P < 0.0001). In J6/JFH cells, it decreased by 12%, 55%, and 80.5% following treatment with 1 μM, 5 μM, and 10 μM Vit D, respectively ( P < 0.0001). There was a significant increase of Vit D between chronic hepatitis C groups, ranging from 4.4 ± 5.6 ng/mL in group A ( n = 44), to 17.2 ± 11.6 ng/mL in group B ( n = 44), and 32.5 ± 37.5 ng/mL of group C ( n = 44) ( P < 0.001). Advanced fibrosis (odds ratio = 0.13, 95% confidence interval = 0.04-0.41, P < 0.001) and Vit D deficiency (<10 ng/mL) (odds ratio = 0.11, 95% confidence interval = 0.03-0.43, P = 0.001) were predictive of SVR in the multivariate regression analysis. Conclusion Vitamin D decreases HCV replication and also contributes to early treatment viral kinetics. [ABSTRACT FROM AUTHOR]

Background and Aim Chronic hepatitis C virus ( HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance ( IR) and lipid profiles with chronic hepatitis C ( CHC) patients in Taiwan. Methods We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol ( HDL- C), low-density lipoprotein cholesterol ( LDL- C), triglycerides ( TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment ( HOMA-IR) were tested. Results When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR ( P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level ( P = 0.023), total cholesterol, and HDL- C and LDL- C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Conclusions Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics. [ABSTRACT FROM AUTHOR]

Background/Aims Pre-diabetes is a risk factor for type 2 diabetes mellitus ( DM) development. This study aimed to elucidate the impact of treatment response on sequential changes in glucose abnormalities in pre-diabetic chronic hepatitis C ( CHC) patients. Methods Chronic Hepatitis C patients with a baseline haemoglobin A1 C ( A1 C) range 5.7-6.4% who achieved 80/80/80 adherence were prospectively recruited. All patients received current peginterferon-based recommendations. The primary outcome measurement was their A1 C level at the end of follow-up ( EOF). The interaction between variants of the IL28 B gene and outcomes of glucose metabolism was also measured. Results A total of 181 consecutive CHC patients were enrolled. The mean A1 C at EOF was 5.82 ± 0.41%, which was significantly lower than the baseline level (5.93 ± 0.21%, P < 0.001). At EOF, 63 (34.8%) patients became normoglycaemic, whereas 10 (5.5%) patients developed DM. The sustained virological response ( SVR) rates of 63 normoglycaemics, 108 pre-diabetics and 10 diabetic patients at the EOF were 92.1%, 84.3% and 50% respectively (normoglycaemics vs. diabetics P = 0.003; pre-diabetics vs. diabetics P = 0.02). Achievement of an SVR was the only predictive factor associated with normoglycaemia development at EOF by multivariate logistic regression analysis (Odds ratio = 2.6, P = 0.04). The prevalence of the interleukin 28 B rs8099917 TT variant in patients who developed DM (70.0%) at EOF tended to be lower than that in patients with pre-diabetics (87.0%) or normoglycaemics (92.1%). Conclusion Successful eradication of HCV improves glucose abnormalities in pre-diabetic CHC patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) proteins can activate the PI3K/Akt pathway which is involved in multiple cellular functions such as inflammatory cell activation and liver fibrosis. The aim of the present study was to elucidate the correlation between Akt expression and liver fibrosis staging in chronic hepatitis C (CHC) patients. Paraffin-embedded liver sections from 133 consecutive treatment-naïve CHC patients were recruited. The expression features of Akt were analyzed using immunohistochemical methods and the results were compared with histological, virological and biochemical profiles. The 73 patients with high Akt expression carried higher histological activity index scores (6.52 ± 2.5 vs 5.62 ± 2.4, P = 0.04) and advanced fibrosis (72.7% vs 26.3%, P < 0.01) than other 60 patients with low Akt expression. The high Akt expression showed a significant incremental trend dependent on fibrosis stages, from 33.3% of F0 to 85.7% of F4 ( P = 0.005). Akt expression was not correlated with degrees of steatosis and virological features of HCV infection, such as viral load and genotypes. Multivariate logistic regression analysis showed advanced fibrosis was the most significant factor associated with high Akt expression (odds ratio = 3.16). Hepatic Akt expression correlated with advanced liver fibrosis in CHC patients. [ABSTRACT FROM AUTHOR]

Abstract Background To elucidate the incidence of the rare cases of icteric type hepatocellular carcinoma (IHCC), we conducted a retrospective study. The clinical outcomes of IHCC cases were also analyzed. Methods From January 1986 to December 1997, newly diagnosed HCC cases were evaluated and reviewed from an admission registration database in a medical center. Patients who had HCC tumors which were located within biliary tracts, and caused obstructive jaundice as the initial clinical manifestation of HCC, were defined as cases of IHCC. Besides clinical manifestations, the outcomes and survival times of various treatment strategies among the IHCC cases were compared retrospectively. Results The incidence of IHCC was 0.53% (10/1897). The median age of the 10 IHCC patients (seven men, three women) was 56.1 years (range = 41–72 years). Most primary HCC lesions (80%) were of expansive type: either single nodular type or multinodular type. All the patients eventually died of cholangitis and sepsis. Besides biliary drainage, seven patients of moderate to good liver reserve function received transarterial chemoembolization (TACE) for palliative treatment, and three of these received additional radiotherapy (R/T) because of the limited effect of TACE (total dosage ranged from 1600 to 5000 cGy). One patient received only radiotherapy (total dosage 1600 cGy) because of having a single tumor and poor liver reserve function. The median survival time among those eight patients who received palliative treatment was 13.4 months (range = 8–26 months), which was significantly longer than for the other two patients without treatment (2 and 4 months). Conclusions Icteric type hepatocellular carcinoma (IHCC) is a rare presentation of HCC. Palliative treatment strategies, including TACE and/or R/T showed a beneficial effect in improving the survival time. [ABSTRACT FROM AUTHOR]

Background/aims: Pretreatment insulin resistance (IR) is associated with treatment response to peginterferon plus ribavirin (PegIFN/RBV) combination therapy in chronic hepatitis C (CHC) infection. However, the impact of PegIFN/RBV therapy on both IR and β-cell function in CHC patients has rarely been investigated., Methods: A total of 277 non-diabetic patients treated with PegIFN-α and weight-based RBV, with 80/80/80 adherence, were recruited. Their IR and β-cell function by homeostasis model assessment model (HOMA-IR and HOMA-%B) before treatment and at 24 week after treatment [end of follow-up (EOF)] was measured., Results: A sustained virological response (SVR) was achieved by 79.4% (220/277) of all patients: 63.6% (75/118) of genotype-1 and 91.2% (145/159) of genotype-non-1 patients. There was no significant change of HOMA-IR post-therapy (2.25 ± 2.46 vs 2.04 ± 2.12, P=0.42). By contrast, there was a significant reduction of HOMA-%B of all patients at EOF (122.9 ± 145.2 vs 92.4 ± 73.2, P=0.001), particularly in those responders (119.1 ± 142.1 vs 89.6 ± 70.3, P=0.002). In 80 patients with high baseline HOMA-IR, both HOMA-IR and HOMA-%B decreased significantly at EOF, irrespective of SVR achievement., Conclusion: This study demonstrated pancreatic β-cell function was ameliorated by PegIFN/RBV therapy in CHC patients, particularly in those responders., (© 2011 John Wiley & Sons A/S.)