Summary
Background
Lipid‐lowering effect was observed during treatment with tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB). However, the metabolic features in patients switching ...from TDF to tenofovir alafenamide (TAF) remain unclear.
Aims
To compare the impacts of switching from TDF to TAF or from entecavir to TAF on body weight and metabolic features in patients with CHB.
Methods
This was a multi‐centre, prospective, observational study in patients with CHB on TDF or entecavir who switched to TAF. Baseline characteristics, lipid profile and sugar profile were determined. This study received IRB approval from each hospital.
Results
We enrolled 177 patients on TDF (99) or entecavir (78) and followed them for 48 weeks after the switch to TAF. At baseline, TDF‐experienced patients had lower serum triglyceride, total cholesterol, high‐density lipoprotein (HDL) cholesterol and low‐density lipoprotein (LDL) cholesterol than entecavir‐experienced patients. The switch from TDF to TAF significantly increased body weight, triglyceride, total cholesterol, HDL, LDL, fasting glucose, glycaemic haemoglobin, insulin and insulin resistance. The switch from entecavir to TAF did not affect these measures. There was no significant difference in atherosclerotic cardiovascular disease risk scores between groups.
Conclusions
The switch from TDF to TAF was associated with weight gain, derangements of lipid profile, and increased insulin resistance in patients with CHB. Long‐term effects on these metabolic features need further investigation.
Body weight increase and metabolic derangements after TDF switch to TAF in patients with chronic hepatitis B.
High dosage and longer duration of antiviral treatment has been suggested to treat cryoglobulinemia patients. We aimed to investigate the efficacy of antiviral treatment in cryoglobulinemia patients ...and analyze the associated factors of persistent cryoglobulinemia.
Totally 148 patients after completion of anti-HCV treatment were enrolled in our study. Serum cryoglobulinemia precipitation was assessed and analyzed for the associated factors after antiviral therapy.
Fifty-one (34.5%) out of 148 patients were positive for serum cryoglobulinemia after completion of antiviral therapy. In multivariate analysis, advanced fibrosis (Odds Ratio OR- 4.13, 95% Confidence Interval 95% CI- 1.53-11.17, p = 0.005) and platelet counts (OR-0.98, 95% CI- 0.97-0.99, p = 0.010) were independently and significantly associated with persistent cryoglobulinemia. The factors associated with the persistent cryoglobulinemia in SVR patients were advanced fibrosis (OR-1.93, 95% CI- 1.02-3.65, p = 0.041) and platelet count (OR-0.98, 95% CI- 0.96-0.99, p = 0.041) by multivariate analysis. Multivariate logistic regression analysis showed persistent (OR-4.83, 95% CI- 1.75-13.36, p = 0.002) was significantly associated with advanced fibrosis in patients with cryoglobulinemia follow up after antiviral therapy.
The prevalence of the persistent cryoglobulinemia is 34.5% after completing antiviral therapy and it is associated with advanced fibrosis, also HCV clearance.
Background and Aim
Reducing post‐absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study ...analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis.
Methods
A meta‐analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels.
Results
Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, −0.425, and −0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of −0.320 and −0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child–Pugh score.
Conclusions
The overall results of the meta‐analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.
Clinical manifestations of phlebosclerotic colitis (PC) exhibit significant variability, necessitating diverse treatment strategies depending on disease severity. However, there is limited research ...exploring the relationship between imaging findings and disease severity. Hence, this retrospective study aimed to analyze the correlation between computed tomography (CT) findings, colonoscopic features, and disease severity. This study compared the abdominal CT characteristics, colonoscopy findings, and treatment modalities of 45 PC patients. CT images were assessed for the severity of mesenteric venous calcification, maximum colonic wall thickness, number of involved colonic segments, and presence of pericolic inflammation. Colonoscopic images were assessed for dark purple discoloration mucosa, erosive and ulcerative lesions, mucosal edema, luminal narrowing, and the number of involved colonic segments. In addition, patients were categorized into three groups: the observation (n = 15), medical treatment (n = 19), and operation (n = 11) groups. In CT images, a significant difference in pericolic inflammation (p = 0.039) was observed among groups. Further, significant differences in dark purple discoloration mucosa (p = 0.033), erosive or ulcerative lesions (p < 0.001), mucosal edema (p < 0.001), luminal narrowing (p = 0.012), and the number of involved colonic segments (p = 0.001) were observed in colonoscopy. Moreover, we found positive correlations between CT and colonoscopy features. In conclusion, CT manifestations and colonoscopy findings exhibited correlation with disease severity in PC. When limited to one diagnostic tool, observations from that tool can infer potential manifestations of the alternative tool.
Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous ...clinical studies. This trial evaluates the pharmacokinetics of 400 μg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 μg.
Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 μg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed.
Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL−1. AUClast was 9364.292 h∗ng mL−1 and AUCinf was 11084.317 h∗ng mL−1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL−1.
Ropeginterferon alfa-2b at 400 μg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 μg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.
Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this ...study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology.
Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models.
The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable.
Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment.
Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate ...aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19.
This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19.
Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) 1.70-305.38,
= 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI 1.12-100.31,
= 0.039), PT-INR (OR: 19.81, 95% CI 1.31-299.49,
= 0.031), hs-CRP (OR: 1.02, 95% CI 1.01-1.02,
= 0.001), albumin level (OR: 0.08, 95% CI 0.02-0.39,
= 0.002), and use of vasopressors (OR: 4.98, 95% CI 1.27-19.46,
= 0.021) were associated with the mortality.
The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.
Background & Aims Dual chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is common in areas endemic for either virus. Combination therapy with ribavirin and pegylated ...interferon (peginterferon) is the standard of care for patients with HCV monoinfection. We investigated the effects of combination therapy in patients infected with both HBV and HCV (genotypes 1, 2, or 3). Methods The study included 321 Taiwanese patients with active HCV infection; 161 also tested positive for hepatitis B surface antigen (HBsAg) and 160 were HBsAg-negative (controls). Patients with HCV genotype 1 infection received peginterferon alfa-2a (180 μg) weekly for 48 weeks and ribavirin (1000–1200 mg) daily. Patients with HCV genotypes 2 or 3 received peginterferon alfa-2a weekly for 24 weeks and ribavirin (800 mg) daily. At 24 weeks posttreatment, patient samples were examined for a sustained virologic response (SVR) against HCV (serum HCV levels decreased to <25 IU/mL). Results In patients with HCV genotype 1 infection, the SVR was 72.2% in dually infected patients vs 77.3% in monoinfected patients after treatment. For patients with HCV genotype 2/3 infections, the SVR values were 82.8% and 84.0%, respectively, after treatment. Serum HBV DNA eventually appeared in 36.3% of 77 dual-infected patients with undetectable pretreatment levels of HBV DNA; this was not accompanied by significant hepatitis. Posttreatment HBsAg clearance was observed in 11.2% of 161 dual-infected patients. Conclusions Combination therapy with peginterferon alfa-2a and ribavirin is equally effective in patients with HCV monoinfection and in those with dual chronic HCV/HBV infection.
Background & Aims A substantial proportion of hepatitis C virus genotype 1 (HCV-1) patients achieved a sustained virological response (SVR, HCV RNA seronegative throughout 24 weeks of post-treatment ...follow-up) after 24 weeks peginterferon/ribavirin therapy. We explored the role of interleukin-28B genotype in identifying patients who responded to the regimen. Methods Interleukin-28B rs8099917 genotype was determined in 226 HCV-1 patients with 24 weeks peginterferon/ribavirin. Results Compared to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, HCV RNA seronegative at treatment week 4, 54.0% vs. 17.9%, p <0.001) and SVR (64.7% vs . 25.6%, p <0.001) rates, and lower relapse rate (28.0% vs . 54.5%, p = 0.01). Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/ 95% confidence intervals OR/CI: 6.24/2.34–16.63), followed by lower viral loads (OR/CI: 5.29/2.81–9.93) and age (OR/CI:0.94/0.91–9.97). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 22.23/9.22–53.58), followed by the carriage of rs8099917 TT genotype (OR/CI: 3.38/1.18–9.65), lower viral loads (OR/CI: 2.23/1.00–4.93) and ribavirin exposure dose (OR/CI: 1.17/1.06–1.30). The determinant power of rs8099917 genotype on SVR was mainly restricted to non-RVR patients, particularly those with higher baseline viral loads. Combination of the two pretreatment predictors, interleukin-28B genotype and baseline viral loads, could predict treatment efficacy with a positive predictive value of 80% and a negative predictive value of 91%. Conclusions Interleukin-28B genotype could help identifying patients who are or are not candidates for an abbreviated regimen before treatment.
Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week ...injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients.
Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24).
SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively.
Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.
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