Treatment Of Hcv In The Setting Of Hbv Coinfection
All individuals with chronic HCV infection should be tested for HBV infection. Testing should include HBsAg, anti-HBc and anti-HBs serology . Current hepatitis B infection is defined by HBsAg positivity, with chronic hepatitis B infection defined as presence of infection for more than 6 months . All individuals with current HBV infection should be referred for specialist management. Past HBV infection is defined by HBsAg negativity, positive anti-HBc ± positive anti-HBs serology . Occult hepatitis B infection is very rare, but is defined by positive HBV DNA in the absence of HBsAg in most cases, the HBV DNA level is very low anti-HBc is normally positive.
Table 7. Definitions of hepatitis B virus infection, by HBV test results
In the absence of further data at this time, the following conclusions have been drawn about risk of HBV reactivation. There is a risk gradient for the occurrence of HBV reactivation, wherein HBsAg-positive individuals have a moderate risk of HBV reactivation. HBsAg-positive people should have HBV DNA levels measured at baseline and should be considered for antiviral therapy according to current guidelines . If antiviral therapy for HBV is not indicated, active monitoring of ALT and HBV DNA levels should be performed during HCV treatment .
History Of Hbv Testing
Only 302 patients had been tested for HBsAg prior to the study according to data collected from routine medical records and patients interviews. Of these, 34 had been found positive. Nine of these 34 patients were HBsAg negative at the time of the present study. Thus, of the 159 patients who were HBsAg positive at the time of the present study, only 25 had a known HBV coinfection prior to the study.
HBV testing had been performed prior to ART initiation in 151 patients , the day of ART initiation in 21 patients , and after ART initiation in 123 patients . The proportion of patients tested for HBsAg ranged from 0.8 to 72.5% according to the individual hospital .
Factors associated with a history of HBV testing are shown in Table . A history of HBV testing was lower in women than in men . By contrast, a history of HBV testing was higher in patients with a secondary or higher educational level than in those with a lower school educational level , and higher in patients who initiated ART in 2010 or later than in those who started ART prior to 2010 . Finally, a history of HBV testing was higher in patients with increased ALT level . It is worth noting that a history of HBV testing was not associated with any hospital-related characteristic such as the region, setting and administrative sector of study hospital, type of HIV service, and task-shifting of ART prescription renewals or follow-up consultations to nurses.
Study Design And Patients
In this multicenter, open-label trial, eligible patients were 20 years of age or older with chronic infection with HCV genotype 1 or 2 and HBV. Chronic HCV was documented by prior medical history or liver biopsy, and chronic HBV was documented through medical records or via positivity for HBsAg or HBV DNA for at least 6 months. Patients with compensated cirrhosis were included in the study. Major ineligibility criteria were receipt of HBV treatment within the prior 6 months, clinical evidence of hepatic decompensation, or presence of HCC. Full eligibility criteria are provided in the protocol. All patients provided written informed consent.
Patients received a fixed-dose combination tablet of LED/SOF, 90/400mg, administered orally once daily for 12 weeks. Patients were followed for 108 weeks after treatment.
The study protocol was approved by the ethics committee of each institution before study initiation. The study was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice Guidelines and the Declaration of Helsinki. All authors had access to the study data and reviewed and approved the final manuscript.
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Hepatitis B And C Virus Considerations In Covid
Along with the pulmonary effects of coronavirus disease 2019 , numerous reports have indicated multiorgan involvement such as gastrointestinal, cardiovascular, and neurologic manifestations in patients who have contracted the virus.1 Additionally, up to 50% of patients with COVID-19 may experience hepatic manifestations ranging from asymptomatic abnormalities in hepatic biochemical tests to the rare case of acute liver failure, according to a review published in May 2020 in Clinical Liver Disease.2
The cause for hepatic manifestations is unclear at this stage and may be caused by a variety of reasons, such as a manifestation of a systemic illness, ischemic liver injury, immunemediated liver injury, druginduced liver injury, or a direct cytopathic effect of the virus, wrote K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the Hospital of the University of Pennsylvania in Philadelphia.2
Available findings to date suggest a low incidence of COVID-19 in patients with HBV and HCV in the United States. A case series of 5700 patients receiving treatment for COVID-19 in multiple hospitals in the New York City area identified HBV and HCV infections in 0.1% and < 0.1% of patients, respectively.4
In an observational Chinese study, 2 of 31 patients with COVID-19 were found to have chronic HBV infection, and these patients showed delayed SARS-CoV-2 clearance compared with HBV-negative patients .6
Availability Of Data And Materials
Due to French law there are restrictions on publicly sharing the data of this study. French law requires that everyone who wishes to access cohort data or clinical study data on humans must make a request to the French Data Protection Authority , by filling in a form which can be provided by Christian Laurent at the IRD . For further information, please see: .
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Risk And Management Of Hbv Reactivation Post Hcv Cure Risk Of Hbv Reactivation In The Era Of Daa
HBV activity may reactivate during anti-HCV therapy in co-infected patients . Our prior data demonstrated that by using pegIFN plus RBV to treat co-infected patients, reactivation of HBV DNA was found in 61.8% of patients with low pre-treatment serum HBV DNA level. The reactivation may occur either during or after the end of IFN-based therapy .
After the introduction of DAA for the treatment of chronic hepatitis C, there is an increased awareness of HBV reactivation in CHC patients co-infected with HBV treated with DAAs. An earlier systematic review and meta-analysis compared the rate of HBV reactivation in CHC patients co-infected with HBV treated with IFN-based therapy, versus those with DAAs . Overall, the pooled incidence rate of HBV reactivation among CHC patients with HBV co-infection was similar between those treated with IFN-based therapy and DAAs . Interestingly, HBV reactivation was noted to occur much earlier in those treated with DAAs in comparison to those receiving IFN-based therapies. The risk of hepatitis due to HBV reactivation was also higher in those receiving DAA versus IFN-based therapy .
Demographics And Risk Behavior
The study participants comprised almost equally of males and females . Samples were representative of 13 regions of Kazakhstan: Akmola , Aktobe , Atyrau , East Kazakhstan , Karaganda , Kostanay , Kyzylorda , Mangystau , North Kazakhstan , Pavlodar , Turkistan , West Kazakhstan , Zhambyl and 2 cities with status of State, i.e., Almaty and Nur-Sultan . The study group comprised patients with mean age of 39 years, while 24% of the patients were aged 3539 yr, followed by 4044 yr and 3034 yr .
Demographic information of study group with respect to: Gender, Region of residence, Age, Year of HIV diagnosis, Risk factors, Travel history. Distribution of males and females among study participants. Distribution of HIV positive cases among regions of Kazakhstan, shown as n . Representation of various age groups among the study participants. Year of HIV diagnosis among the study participants. Reported high-risk groups among the study participants. Travel history of study participants.
The majority of study participants were diagnosed with HIV during the year 2010 to 2017 . The most common high-risk behavior was injection drug use , followed by sexual contact with PLWH , with PWID , or with sex worker . Only 5% of study participants had traveled abroad, with 76% travelling to former Soviet Union countries, including Russia , Kyrgyzstan , Azerbaijan and Uzbekistan . The remaining 6 patients travelled to non-FSU countries: 3 each to Turkey and China. .
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Treatment Of Patients With Hcv/hbv Co
Our previous data confirmed the efficacy of pegIFN plus RBV in the treatment of co-infected patients with active hepatitis C . The durability of hepatitis C clearance in HCV/HBV co-infected patients was later demonstrated by a 5-year prospective follow-up study . This leads to the suggestion that the efficacy and durability of HCV SVR by using pegIFN alfa and ribavirin therapy were satisfactory and not influenced by HBV co-infection. In addition to the cure of HCV infection, pegIFN-based therapy may also help control the chronic HBV infection in patients with HCV/HBV co-infection. During a 5-year post-treatment follow-up, the rate of HBsAg seroclearance was 5.4% per year . Another study, which investigated the outcomes in 192 HCV/HBV co-infected patients after anti-HCV therapy, also found that 67 patients had a favorable outcome of HBsAg seroclearance . The probability was 5.7 per 100 person years. In addition, a pretreatment HBV DNA level of 300 IU/mL served as an independent predictor for the outcome.
For patients with HCV/HBV co-infection, we hope treatment can decrease the risk of HCC development and liver-related mortality in the long term. In Taiwan, we analyzed nationwide databases and conducted a case-control study. We found that the treatment of co-infected patients using pegIFN plus RBV indeed reduced risk of HCC development and liver-related mortality .
Hbv Virologic And Clinical Reactivation
Throughout treatment and 108 weeks of follow-up, HBV virologic reactivation occurred in 73% of patients . A greater proportion of patients with virologic reactivation had HBV DNA< LLOQ at baseline than those who did not have reactivation . Clinical reactivation occurred in 9% of participants , with similar percentages having baseline HBV DNA< LLOQ vsLLOQ .
The majority of cases of HBV virologic reactivation occurred during the period encompassing treatment and week 12 of follow-up by follow-up week 12, 70 patients had HBV reactivation . One-quarter of patients had HBV virologic reactivation by week 4 of treatment. The virologic reactivation was transient in 7.4% . The occurrence of clinical reactivation was generally more delayed relative to HBV virologic reactivation . Of the 10 patients who experienced clinical reactivation, 5 patients did so by week 12 of follow-up, and 4 did so through weeks 1248 of follow-up.
Timing of hepatitis B virologic and clinical reactivation. EOT, end of treatment FU, follow-up.
To demonstrate the independent profile of serum HBV DNA before the treatment of DAA, we retrospectively collected virologic data from 17 enrolled patients. Their HBV DNA profiles are shown in Supplementary Table 1. Briefly, the pretreatment serum HBV DNA levels remained stationary, suggesting that the change of serum HBV DNA level after start of DAA therapy was not from the fluctuating nature of the HBV DNA levels.
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While Hbv Infection Does Not Enhance The Rlh System Hcv Infection Does Enhance The Rlh System
HBV or HCV infection of primary human hepatocytes from chimeric mice. Primary hepatocytes from chimeric mice were incubated with HBV for 1 day or with HCV for 3 days. Schematic of the HBV experimental procedure. Representative pictures of immunofluorescent staining to determine HBc- and HBc-positive cell ratios on the indicated day The white bar in the pictures is a scale bar indicating 500µm. HBV DNA and HBs antigen in 3-day cultured medium . Schematic of the HCV experimental procedure. Representative pictures of immunofluorescent staining to determine NS5A- and NS5A-positive cell ratios on the indicated day . The white bar in the pictures is a scale bar indicating 500µm. HCV RNA in 5-day cultured medium . mRNA expression levels of RIG-1, ISG15 and ISG56 0 day and 19 days after HBV incubation . mRNA expression levels of RIG-1, ISG15 and ISG56 after HCV inoculation . *p< 0.05, **p< 0.01, HBV-infected cells or HCV-infected cells vs. non-infected cells .
What Are The Side Effects Of Treatment
Some people stop therapy because of side effects. Since hepatitis C can lead to liver damage, cirrhosis, and liver cancer if not treated, its vital to stick with a treatment plan.
Newer drugs have fewer severe side effects than pegylated interferon and ribavirin. Nevertheless, you may feel some effects while taking hepatitis C medication. Side effects can include:
- nausea, vomiting, or diarrhea
- appetite loss or weight loss
Serious side effects can occur with pegylated interferon and ribavirin treatment. If youre taking these medications, you should be monitored for these serious side effects:
- light sensitivity in the eyes
- trouble breathing because of lung tissue inflammation
- suicidal thoughts, depression, or irritability
- thyroid disease
- elevated liver enzymes
- autoimmune disease flares
Some medications arent recommended if theres evidence of liver damage, like cirrhosis . A co-infection with HIV also affects medication options.
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Learning Objective Performance Indicators
- Explain the impact of HIV on coinfection with HCV
- Discuss sustained virologic response outcomes demonstrated in key studies using direct-acting antiviral agents to treat HCV in persons with HIV coinfection
- Differentiate HCV treatment duration for HCV monoinfection versus HCV-HIV coinfection
- Summarize recommendations for monitoring persons with HCV-HIV coinfection after initiating antiretroviral therapy
- Highlight drug interactions from the perspective of direct-acting antivirals and antiretroviral medication classes
Coinfection In The Pediatric Population
While the aforementioned studies refer to coinfected adults, similar trends towards more severe liver disease exist in coinfected children. One study of chronic hepatitis in children ages 517, including 10 children with coinfection, demonstrated a greater degree of necroinflammation in the coinfected group.34 There was a more significant difference when compared to HCV monoinfected children versus HBV monoinfection. While this information is useful for understanding the natural history and progression of liver disease in coinfected children, it is difficult to interpret with regard to implications for treatment. The USA Federal Drug Administration recently approved use of direct-acting antivirals for HCV in children aged 1217, but these agents are not approved for use in younger children.35 The increased severity in coinfected children highlights a potential benefit for expansion of DAA use. However, given the current guidelines for treatment, children under 12 years of age should be studied separately from those ages 1217 since the impact on treatment is different.
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Demographic And Laboratory Features Of The Study Subjects
A total of 100 HBV/HCV coinfected patients were enrolled in this study. There were 37 men and 63 women, and the mean patient age was 62.3 years . A total of 15 patients were HBV-inactive/HCV-inactive, 63 patients were HBV-inactive/HCV-active, 14 patients were HBV-active/HCV-inactive and 8 patients were HBV-active/HCV-active. A total of 71 patients were active HCV and 22 were active HBV. All of the included patients were seronegative for HBeAg, except one patient with HBeAg-positive CHB in the BICA group.
Table 1 Clinical and virological characteristics of the patients
Based on viral load, patients were placed into one of the following groups: BICI , BICA , BACI , or BACA . The demographic, clinical, and virological characteristics of each group are presented in Table . HBV DNA, HBsAg, HBcrAg, and HCV RNA showed statistically significant differences among the four groups while HBV pgRNA did not. Liver enzyme , cirrhosis, FIB-4, and AFP levels in the BICA and BACA groups were higher than those in the BICI and BACI groups. There were no statistically significant differences among the four groups regarding age, sex, fatty liver, alcoholism, albumin, total bilirubin, eGFR, prothrombin time, and platelet count.
Hepatitis B Reactivation In Patients Treated With Direct
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Rna Extraction And Rt
Total RNA was extracted using an RNeasy Mini Kit . The extracted RNA was treated with DNase to analyse pgRNA. To synthesize cDNA, the extracted RNA was reverse transcribed with Rever Tra Ace qPCR RT Master Mix . For RT-PCR, the following primers in TaqMan gene expression assays were used: human -actin , human RIG-I , human IRF3 , human ISG15 , and human ISG56 . To analyse pgRNA, the following forward and reverse primer set was prepared: 5-TGTCCTACTGTTCAAGCCTCCAA-3 and 5-GAGAGTAACTCCACAGTAGCTCCAA-3 . Human -actin was used as the internal control, and all mRNA expression levels were normalized to the levels of the internal control mRNA.
Who Can I Talk With During Treatment
Since hepatitis C treatment plans last several weeks, you should regularly attend medical appointments. Your doctor may have a list of local groups where you can find emotional support.
There may also be other resources like community nurses and walk-in clinics. With this information, youll know where to go for help between appointments.
Another option is to explore the online hepatitis C community, where people share their experiences with hepatitis C.
For example, the Inspire hepatitis C group allows people to connect, share stories, discuss treatment, and more.
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