ENDOSCOPE CONTAMINATION FROM HBV‐ AND HCV‐POSITIVE PATIENTS AND EVALUATION OF A CLEANING/DISINFECTING METHOD USING STRONGLY ACIDIC ELECTROLYZED WATER

Background: It is well known that strongly acidic electrolyzed water (SAEW) has a potent bactericidal effect. We examined residual viruses on endoscopes that were used in hepatitis B virus (HBV)‐positive and hepatitis C virus (HCV)‐positive patients and evaluated the effectiveness of SAEW in cleaning/disinfecting the endoscopes. Methods: A random sample of endoscopes used in 109 endoscopies on HBV‐positive patients and 107 endoscopies on HCV‐positive patients, who underwent upper gastrointestinal endoscopy for various reasons was taken to determine the degree of HBV and HCV contamination. Samples were taken using 10 mL of physiological saline injected through the forceps channel of each endoscope and collected at the distal end to be assayed using polymerase chain reaction (PCR). After examination, each endoscope was treated with air aspiration, then 200 mL of tap water that contained an enzyme detergent was absorbed, and SAEW was aspirated after cleaning with a brush. After each procedure, PCR was used for comparison and to identify any residual viruses. Results: In saline collected after air aspiration, viruses were detected in 39/109 endoscopes used in HBV patients and in 20/107 endoscopes used in HCV patients. In the saline aspirated with tap water containing an enzyme detergent, HBV was detected in 12/109 endoscopes and HCV was detected in 6/107 endoscopes. However, neither HBV nor HCV was detected after the endoscopes were cleaned manually with a brush and disinfected with SAEW. Conclusion: Endoscopes contaminated with HBV and HCV are effectively cleaned and disinfected by SAEW.     

Virus‐neutralizing antibodies to hepatitis C virus

For a long time, the lack of an appropriate cell culture system has hampered the study of neutralizing antibody responses against hepatitis C virus (HCV). However, the last decade has seen the development of several model systems that have significantly advanced our understanding of viral entry and antibody neutralization. Studies of acutely infected patients suggest that a strong and early production of neutralizing antibodies may contribute to control the virus during the acute phase of HCV infection and facilitate viral elimination by cellular immune responses. It also emerges that the early antibody response mainly targets hypervariable region 1 (HVR1) of the envelope glycoprotein E2. This host response can lead to viral escape from neutralization by rapid amino acid changes in this hypervariable region. In contrast, cross‐reactive neutralizing antibodies seem to appear later during HCV infection, and several mechanisms contribute to reduce their accessibility to their cognate epitopes. These include the masking of major conserved neutralizing epitopes by HVR1, specific N‐linked glycans and the lipid moiety of the viral particle. Other potential mechanisms of evasion from the neutralizing antibody response include a modulation by high‐density lipoproteins and interfering antibodies as well as the capacity of the virus to be transferred by cell‐to‐cell contacts. Finally, the recent identification of several highly conserved neutralizing epitopes provides some opportunities for the design and development of vaccine candidates that elicit a protective humoral immune response.     

Effect of hepatitis B virus on steatosis in hepatitis C virus co‐infected subjects: A multi‐centre study and systematic review

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi‐centre cohort of HBV‐HCV subjects, and by performing a systematic review and meta‐analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV‐HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV‐HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV‐HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV‐HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV‐HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV‐HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53‐1.6) although there was significant heterogeneity (I² 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV‐HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV‐induced steatogenesis by HBV in certain subgroups of patients.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

Decline of cellular activation in non‐B cells after rituximab treatment in hepatitis C‐associated mixed cryoglobulinemia vasculitis

Mixed cryoglobulinemic vasculitis is associated with the monoclonal expansion of pathognomonic B cells in chronic hepatitis C. Recently, treatment with B‐cell depletion, including rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from the active disease. We investigated whether B‐cell depletion therapy has an impact on activation of non‐B cells in the periphery. Results demonstrated that B‐cell depletion therapy is associated with a statistically significant decline in activated T cells, from pretherapy to follow‐up while on rituximab therapy: CD4+ CD38+ HLA‐DR+ (DR+), CD8+ CD38, CD8+ CD38+ DR+, and CD8+ DR+. Birmingham Vasculitis Activity Score and cryoglobulin had a strong correlation coefficient (R) of 0.72 (P=.0005), while cryoglobulin showed moderate correlation with CD8+ DR+ (R=.61), CD3+ CD38+ DR+ (R=.57), CD3+ DR+ (R=.50), CD4+ CD38+ DR+ (R=.53), CD4+ DR+ (R=.52), and CD8+ CD38+ DR+ (R=.67). These results suggest B‐cell expansion has a direct and indirect effect on the pathogenesis of Hepatitis C‐associated mixed cryoglobulinemic vasculitis.     

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus‐co‐infected patients (ANRS CO13‐HEPAVIH)

Liver steatosis is common in human immunodeficiency virus (HIV)‐hepatitis C virus (HCV)‐co‐infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV‐HCV‐co‐infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13‐HEPAVIH is a French nationwide multicentre cohort of HIV‐HCV‐co‐infected patients. Medical and socio‐behavioural data from clinical follow‐up visits and annual self‐administered questionnaires were prospectively collected. A cross‐sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use (“never or sometimes”). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV‐HCV‐co‐infected patients. These findings confirm the need for a clinical evaluation of cannabis‐based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.     

Adjuvant epoetin‐β with peginterferon‐α and ribavirin in Japanese ribavirin‐intolerant relapsed patients with chronic hepatitis C genotype 2

Erythropoietin is widely used in the USA and some other Western countries to maintain doses of ribavirin during peginterferon/ribavirin‐based treatment for chronic hepatitis C virus (HCV) infection. However, the impact of erythropoietin on sustained virological response (SVR) is unclear. Here, we report the cases of three Japanese ribavirin‐intolerant relapsed patients with HCV genotype 2 who achieved SVR from retreatment by adding erythropoietin. Three women aged 50, 64 and 68 years with chronic HCV genotype 2 received retreatment with peginterferon‐α and ribavirin. During their prior therapy, HCV RNA became negative according to real‐time polymerase chain reaction at weeks 4–8 in all three patients; however, the total dose of ribavirin was 18.1–30.6% lower than the planned dose, and HCV RNA relapsed post‐treatment. At present, epoetin‐β 24 000 IU was introduced at weeks 2 or 3 of dual‐combination therapy, resulting in a less than 4.2% reduction in the total dose of ribavirin. HCV RNA became negative at weeks 4–8, and all patients achieved SVR. Until the next‐generation antiviral treatments for HCV genotype 2 become available, the addition of erythropoietin to dual therapy can be a treatment of choice for ribavirin‐intolerant relapsed patients.     

Peginterferon‐alpha‐2b plus ribavirin therapy in patients with chronic hepatitis C as assessed by a multi‐institutional questionnaire in Japan

Background and aim: There has so far been no questionnaire report on patients who were treated with peginterferon plus ribavirin (PEG IFN+RBV) therapy. The purpose of this study was to investigate the problems of this therapy by a questionnaire survey. Patients and methods: A survey of 681 patients with chronic hepatitis C who received treatment with PEG IFN+RBV was conducted in the Kyushu region of Japan. Using an original questionnaire, the survey was conducted prior to the treatment, during the third month of treatment, at the completion of treatment or the discontinuation of treatment, and at 6 months after the completion of treatment. Results: It was indicated that the patients had a high level of comprehension and understanding of chronic hepatitis C and PEG IFN+RBV treatment. However, the results also indicated that patients had a high level of anxiety. Side effects were adequately dealt with by physicians. However, dermatological symptoms were not adequately explained to the patients, although they were the second most severe side‐effect. It was also revealed that side‐effects were most distressing during the first and second months after the start of treatment. Conclusion: The questionnaire survey provided new information that has never been reported. It is believed that understanding this information is important for future treatment.     

Risk of diabetes in viral hepatitis B or C patients compared to that in noninfected individuals in Korea, 2002‐2013: A population‐based cohort study

While the association between hepatitis C virus (HCV) infection and diabetes has been established, the relationship between hepatitis B virus (HBV) infection and diabetes remains unclear. Therefore, we compared the association between diabetes development in HBV, HCV and co‐infected (HBV/HCV) patients to that in noninfected participants using population‐based cohort data. We used the National Health Insurance Service‐National Sample Cohort, which consists of 514 791 randomly selected persons among those who underwent health check‐ups from 2002 to 2003 aged 40‐79 years. Adults found to have HBV or HCV infection from 2002 to 2003, without a prior history of diabetes, were selected as subjects. Competing risk regression models were used to estimate cumulative incidence and hazards ratios (HRs) of diabetes development. The cumulative incidences, incidence densities and HRs of diabetes were highest in the co‐infected group, followed by those in the HCV‐, HBV‐ and noninfected groups. The 12‐year cumulative incidences were as follows: 42.0% in HBV/HCV‐, 32.9% in HCV‐, 23.9% in HBV‐ and 18.3% in the noninfected groups. The incidence density per 1000 person‐years was 55.0, 51.5, 38.2 and 28.2 for the HBV/HCV‐, HCV‐, HBV‐ and noninfected groups, respectively. The adjusted HRs for diabetes were 1.90, 1.68 and 1.41 for the HBV/HCV‐, HCV‐ and HBV‐infected groups, respectively. Our findings suggest that both HCV and HBV infections are associated with the development of diabetes; therefore, prevention of, screening for, and treatment of both may reduce the risk of diabetes in these patients.     

Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection

Direct‐acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti‐HBe hepatitis during interferon (IFN)‐free DAA therapy in HBV/HCV co‐infected patients with inactive HBV. A 69‐year‐old male patient was diagnosed with chronic hepatitis due to HBV/HCV co‐infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core‐related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug‐induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti‐HCV DAA therapy and the commencement of anti‐HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co‐infection.     

High levels of circulating N‐terminal pro‐brain natriuretic peptide in patients with hepatitis C

Summary. Many patients chronically infected by hepatitis C virus (HCV) experience symptoms like fatigue, dyspnea and reduced physical activity. However, in many patients, these symptoms are not proportional to the liver involvement and could resemble symptoms of chronic heart failure. To our knowledge, no study evaluated serum levels of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in a large series of patients with HCV chronic infection (HCV+). Serum NT‐proBNP was assayed in 50 patients HCV+ and in 50 sex‐ and age‐matched controls. HCV+ patients showed significantly higher mean NT‐proBNP level than controls (P = 0.001). By defining high NT‐proBNP level as a value higher than 125 pg/mL (the single cut‐off point for patient under 75 years of age), 34% HCV+ and 6% controls had high NT‐proBNP (Fisher exact test; P < 0.001). With a cut‐off point of 300 pg/mL (used to rule out chronic heart failure in patients under 75 years of age) 10% HCV+ and 0 controls had high NT‐proBNP (Fisher exact test; P = 0.056). With a cut‐off point of 900 pg/mL (used for ruling in chronic heart failure in patients with age 50–75) 8% HCV+ patients and 0 controls had high NT‐proBNP (Fisher exact test; P = 0.12). The study demonstrates high levels of circulating NT‐proBNP in HCV+ patients compared to healthy controls. The increase of NT‐proBNP may indicate the presence of a sub‐clinical cardiac dysfunction. Further prospective studies quantifying these symptoms in correlation with echocardiography are needed to confirm this association.