In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the ...molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.
SUMMARY
Background
Chronic hepatitis B has been linked to lymphoma with contradictory results.
Aim
To investigate the association between chronic hepatitis B and lymphoma by using a nationwide ...population‐based cohort.
Methods
Records of patients diagnosed with chronic hepatitis B (hepatitis B virus HBV cohort) or without (non‐HBV cohort) during 2004‐2007 were retrieved from the Taiwan National Health Insurance Research Database. Age, sex, comorbidities, and medical visits were matched using propensity scores between both cohorts, and they were followed up longitudinally until 2012 to determine any new lymphoma development.
Results
A total of 203 031 patients were included in each cohort with a mean follow‐up of 7‐9 years. The lymphoma incidence rate was significantly higher in the HBV cohort than in the non‐HBV cohort (29.4 vs 15.9 per 100 000 person‐years, P < 0.0001). After adjustment for comorbidities and medical visits, HBV infection was found to be an independent risk factor associated with the development of lymphoma (hazard ratio HR: 2.07, 95% confidence interval CI: 1.76‐2.43, P < 0.0001) and non‐Hodgkin's lymphoma (HR: 2.18, 95% CI: 1.80‐2.65, P < 0.0001); specifically with an increased risk of diffuse large B‐cell lymphoma (HR: 2.69, 95% CI: 2.05‐3.52, P < 0.0001), other B‐cell lymphoma (HR: 3.11, 95% CI: 1.89‐5.11, P < 0.0001), and also for multiple myeloma (HR: 1.63, 95% CI: 1.10‐2.42, P = 0.016). The association was significant even after excluding lymphoma development within the first year (HR: 2.08, 95% CI: 1.75‐2.47, P < 0.0001).
Conclusions
Chronic hepatitis B is temporally associated with a 2‐fold increased risk of lymphoma, particularly with B‐cell non‐Hodgkin's lymphoma, and also an increased risk for multiple myeloma.
Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated ...fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis.
From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared.
In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases.
The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria.
Background/Aims
Chronic hepatitis B virus (HBV) infection still poses a major threat to global health. Oligoadenylate synthetase–ribonuclease L (RNase L) antiviral pathway is one of ...interferon‐induced antiviral effectors. The relationship between RNase L and HBV has never been investigated and we aim to examine the serum RNase L levels in patients with different stages of chronic HBV infection.
Methods
The patients were enrolled from 1985 to 2000, who had been HBsAg positive for longer than 6 months, at the National Taiwan University Hospital. In total, 426 patients with chronic HBV infection were included in this study, including 135 inactive carriers, 148 cirrhosis, and 143 hepatocellular carcinoma (HCC) cases.
Results
The RNase L levels increase as the disease severity increases. Higher RNase L levels were associated with higher HBV viral load, and the HBV‐RNase L relationship was replaced by the disease severity status when adding disease status into the model. Compared with inactive carriers, the risk of liver cirrhosis was 60‐fold (odds ratio = 60.8, 95% confidence interval = 3.49–1061) with the highest quintile of RNase L levels, after the adjustment of HBV DNA. The dose–response trend was statistically significant with quintiles and one increment of RNase L level in relation to liver cirrhosis. Similar results were found when HCC was compared with inactive carriers, while there was no association when compared between liver cirrhosis and HCC.
Conclusions
A positive relationship between serum RNase L and HBV viral titers or advanced disease status is uncovered in this study. Further investigation in this area may provide more details of an innate immune response for HBV and opportunity for novel therapeutic strategy.
Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects ...with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
Background & Aims
Large‐scale data regarding the real‐world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) for patients with chronic hepatitis C virus (HCV) infection were limited in ...East Asia. We aimed to evaluate the clinical performance of GLE/PIB in different HCV populations in Taiwan.
Methods
A total of 658 chronic HCV patients with compensated liver diseases receiving GLE/PIB for 8 (n = 549), 12 (n = 103) or 16 (n = 6) weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response at off‐therapy 12 weeks (SVR12). Patient characteristics potentially related to SVR12 and the safety profiles were also assessed.
Results
By evaluable population (EP) and per‐protocol (PP) analyses, the overall SVR12 rate was 98.2% (95% confidence interval (CI): 96.8%‐99.0%) and 99.4% (95% CI: 98.4%‐99.8%). The SVR12 rates were 98.9% (95% CI: 97.6%‐99.5%), 94.2% (95% CI: 87.9%‐97.3%) and 100% (95% CI: 60.1%‐100%) in patients receiving 8, 12 and 16 weeks of treatment respectively. A total of 656 (99.7%) patients completed the scheduled treatment. The SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline. Twenty (3.0%) patients had serious adverse events (AEs), but none were not related to GLE/PIB. The two most common AEs were pruritus (7.8%) and fatigue (5.5%). Two (0.3%) and no patients had ≥3‐fold upper limit of normal (ULN) for total bilirubin and alanine aminotransferase (ALT) levels.
Conclusions
GLE/PIB for 8‐16 weeks is effective and well‐tolerated for patients with chronic HCV infection in Taiwan.
Summary
Background
Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment‐induced sustained virologic response (SVR) in patients on haemodialysis.
Aims
To assess ...the risk of HCV reinfection among patients on haemodialysis with treatment‐induced SVR.
Methods
Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct‐acting antiviral (DAA)‐based treatment received follow‐up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12. The low‐risk general population who achieved SVR12 and who underwent the same post‐SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person‐years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups.
Results
We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post‐SVR12 follow‐up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24. The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval CI: 0.09‐0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10‐0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio HR: 1.39; 95% CI: 0.44‐4.38, P = 0.57).
Conclusions
The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low‐risk general population. HCV microelimination in this special population is feasible once universal screening and scaled‐up treatment are implemented.
374 haemodialysis patients, 1571 low‐risk general population (reference) achieving SVR12 by DAAs or IFN.Incidence rate of HCV reinfection: Haemodialysis: 0.23 per 100 person‐years (PYs).Reference: 0.16 per 100 PYsHazard ratio (HR): 1.39 (95% CI: 0.44‐4.38, P = 0.57).
Smoking interacts with hepatitis B virus (HBV) to increase the risk of hepatocellular carcinoma (HCC), which might be explained by its role in antiviral immunity. We evaluated the potential mediating ...role of viral load and/or alanine aminotransferase (ALT) in the relation of smoking with HBV‐associated HCC risk. Using multiple mediation analyses to analyze data from 209 HCC cases and 1,256 controls nested within a cohort of 4,841 male HBV carriers, we found that the effect of smoking on the risk of subsequent HCC was substantially mediated through viral load (percent mediated, 31.7%; P = 0.0054), and a significant mediation effect by both viral load and ALT was also evidenced. Among the 1,143 subjects with repeated measures of viral load and ALT over periods of up to 16 years, we further observed that a higher number of pack‐years of smoking was associated with higher viral load, maintenance of a high viral load (>4.39 log copies/mL), more severe hepatotoxicity grade, and increased likelihood of ALT ≥80 U/L (odds ratio, 3.14; 95% confidence interval, 1.03‐9.64; odds ratio, 6.06; 95% confidence interval, 1.10‐33.25, respectively, for 10‐19 and ≥20 pack‐years versus nonsmokers) during follow‐up. Furthermore, plasma interferon‐γ levels were reduced in smokers compared with nonsmokers (interferon‐γ‐positive rate, 14.9% versus 28.7%; P < 0.0001) at baseline. Smoking was also associated with a reduced natural killer (NK) cell frequency in peripheral blood, characterized by reduced NK function through a systems immunology approach, after long‐term follow‐up in a subsample (n = 171). The combination of smoking and reduced NK cell frequency further increased viral load and the likelihood of ALT ≥80 U/L. Conclusion: The data highlight a role of smoking in HBV viral load, underlining the importance of smoking prevention and cessation in hepatitis B management.
Early confirmation of sustained virologic response (SVR) or viral relapse after direct‐acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, ...particularly for patients with high risk of nonadherence to posttreatment follow‐ups. A total of 1011 patients who achieved end‐of‐treatment virologic response, including 526 receiving fixed‐dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off‐treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off‐treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval CI: 98.0–98.9) and 100% (95% CI: 66.4–100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed‐dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% 95% CI: 98.9–100 vs. 97.1% 95% CI: 96.2–97.8, p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off‐treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off‐treatment week 12 among patients with HCV who are treated with fixed‐dose pangenotypic DAAs.
PDF
