Acute Hepatitis C Virus Research Articles

Seroprevalence of Hepatitis C virus (HCV) in patients on maintenance haemodialysis at tertiary care hospitals of Pune, Maharashtra, India

Introduction: High prevalence of Hepatitis C virus (HCV) has been reported among the dialysis patients throughout the world. Aim of the study was to evaluate prevalence of HCV in haemodialysis patients at tertiary care hospitals of Pune, Maharashtra, India. Materials and Methods: A cross sectional study design was conducted among 250 patients from five dialysis centres in pune city including both government and corporate hospitals who reported to the nephrology department for haemodialysis in a period of one year. Cases were studied in detail about complete history, clinical and demographical profile as well as several biochemical parameters. A predesigned, pretested questionnaire was used for data collection. SPSS 21.0 version software was used to analyze the data. Result: Prevalence of HCV Infection in patients on hemodialysis was found to be (18.8%). Out of total anti-HCV antibody positive patients (59.6%) were found to be male and (40.4%) were female. Out of total anti-HCV antibody positive cases (72.3%) had been on dialysis for more than 5 years. About (68.1%) of total positive cases received blood transfusion once or more in life time. Conclusion: In developing countries with a high endemic background of HCV infection surveillance programs and efforts to increase awareness, improve diagnosis and facilitate treatment of acute HCV will have far reaching implications for the management of chronic HCV. Thus preventive measures and the adherence to universal precautions for HCV control remain a priority. Keywords: Seroprevalence, Hepatitis C, Haemodialysis, Tertiary care hospitals.

Hepatitis C outbreak in a respiratory care ward associated with frequent injections: Taiwan, 2017.

Healthcare-associated outbreaks of hepatitis C virus (HCV) infection pose serious risks of harm to patients. During May-July 2017, the Taiwan Centers for Disease Control were notified of four patients with acute HCV infection in a respiratory care ward (RCW). To prevent further infection, an investigation was conducted to identify the transmission route and risk factors for infection. We tested patients and staff members of the RCW for HCV, reviewed medical records, observed infection control practices on-site, and undertook a case-control study. We defined cases as individuals who had stayed in the RCW 2 weeks to 6 months prior to the laboratory diagnosis date of the first case and were infected with HCV after admission. Patients who were hospitalized during the same period but whose HCV tests were negative were selected as controls. We used Mann-Whitney U test to compare the frequency of injections among cases and controls. Of 19 staff and 29 patients, we identified four case-patients and one patient with chronic hepatitis C whose HCV RNA similarity was >98%. Compared to the 12 controls, the case-patients received more injections per day (4.4 vs. 0.1; p=0.01). The RCW lacked designated areas and standardized workflows for injection preparation. Disinfection of the environment and equipment was inadequate, which could possibly lead to blood contamination of the environment and parenteral medications. HCV infection was associated with frequent injections and infection control lapses. Healthcare workers should follow safe injection practices and reduce injection frequency to prevent HCV transmission.

A protracted war of human beings against virus: Interpreting for the Nobel Prize in Physiology or Medicine in 2020

On 5th October of 2020, the Nobel committee announced in the Karolinska Institute that the 2020 Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice to commend their contribution in the aspect of discovering hepatitis C virus (HCV). Alter and his team acquired C100-3 protein by utilizing recombinant yeast to express viral sequence segments and found the HCV antibody by performing radioimmunoassay. Houghton and his colleagues successfully created the cDNA library from the serum of non-A and non-B hepatitis patients in bacteriophage. Subsequently, the large-scale blind screening method was performed in the serum of patients, acquired clone 81 from the library screening as the clone 5-1-1 involving short sequences to be the probe, and confirmed HCV ultimately. In 1995, Rice and his collaborators completed the full-length HCV genome sequencing from the 3′ terminal sequence using a quantitatively competitive reverse transcription PCR method and verified the full-length sequence has infectivity. This is the first causative agent entirely discovered by molecular biological techniques in human being’s history. Furthermore, Wakita with his team, acquired a full-length HCV genome from acute HCV patients and transformed viral RNA to Hun-7 cell to generate HCV virion in 2005. On this basis, Rice and his team successfully established the cell-cultured system that can effectively generate HCV with infectivity. According to the WHO latest data, there were approximately 71 million chronic HCV cases and nearly 400000 deaths globally in 2016. About 14% of the total HCV infected individuals worldwide lived in China. As a common infectious pathogen globally, HCV infection may cause severe threats and damages to human health, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The high genetic variation is major characteristics of HCV, which has phylogenetically generated more than 7 genotypes and hundreds of subtypes. The various genotypes and subtypes have distinct geographic distribution and different responses on anti-virus treatment. The resistant mutation for the clinical using drugs including Epclusa (Sofosbuvir and Velpatasvir), is occurring. Moreover, the highly chronic progression render HCV as a silent slayer for human health, and plenty of HCV cases were difficult to be timely diagnosed due to its high proportion of asymptomatic. All these indicated that HCV prevention and control are still facing severe challenges.

Hepatitis C Virus Treatment as Prevention: Challenges and Opportunities in Men Who Have Sex With Men.

Since 2002, a global epidemic of acute hepatitis C virus (HCV) infection has been noted in men who have sex with men (MSM). Transmission of HCV, particularly in the context of traumatic sex practices that increase the risk of blood-blood contacts (eg, anal sex and fisting), was initially found in human immunodeficiency virus (HIV)-coinfected and more recently in HIV-uninfected MSM, especially those receiving pre-exposure prophylaxis (PrEP). Early HCV treatment with all-oral direct-acting antiviral combination therapy has been associated with very high HCV cure rates of up to 100%. Indeed, immediate treatment of recently acquired HCV directly after new HCV diagnosis, or after 4 weeks if no 2-log10 drop in HCV RNA level occurs, promises rapid HCV elimination. Reports from the Netherlands, Switzerland, and the United Kingdom all show that with increased treatment uptake in this particular patient group, dramatic reductions in new HCV infections can be achieved. A general consensus on how to best screen for and manage acute HCV infections, along with broad access to rapid HCV therapy initiation, is crucial to attaining HCV elimination, a goal that is challenged by high HCV reinfection rates among MSM.

Risk Factors Associated with Acute Hepatitis C in Mongolia

Background: Hepatitis C virus (HCV) infection is endemic in Mongolia, with reported prevalence of HCV antibody (anti-HCV) positivity of 11%–16% in the adult population. Healthcare-related risk factors associated with development of acute HCV infection have not been evaluated in this population. Methods:We conducted a prospective, matched case-control study to identify risk factors associated with acute HCV infection in Ulaanbaatar, Mongolia. Cases were aged 18 years with discrete onset of symptoms consistent with acute viral hepatitis as well as jaundice or elevated serum alanine aminotransferase (ALT) levels who were admitted to the National Center for Communicable Diseases during January–October, 2019. Cases were both anti-HCV and HCV RNA positive and tested negative for acute hepatitis A, B, and E. Controls were randomly selected from the Population and Household Database, a national registry of all citizens, and were matched by age and gender. Data collection covered healthcare-associated and other risk factors in the 6 months before symptom onset (cases) or interview date (controls). Adjusted measures of association comparing cases and their matched controls were obtained using a multivariate conditional logistic regression model. Results: We enrolled 35 case patients and 104 controls. Median age of all participants was 44 (range, 23–63) years and 19% (27 of 139) were men. All case patients reported jaundice and loss of appetite; most cases reported nausea, malaise, and abdominal pain (97%, 91%, and 83%, respectively). The median ALT level among case patients was 1,185 IU/L (range, 212–3,349). Case patients were more likely than controls to have been admitted as inpatients (matched odds ratio [mOR], 4.3; 95% CI, 1.5–11.9), to have visited an outpatient clinic (mOR, 3.6; 95% CI, 1.3–10.2), to have had phlebotomy (mOR, 3.3; 95% CI, 1.5–7.5) or endoscopy (mOR, 10.7; 95% CI, 2.2–51.2) as an outpatient procedure, and to have received an injection outside of healthcare settings (mOR, 2.2; 95% CI, 1.0–5.1). Cases were also more likely to have lived in a yurt (mOR, 2.3; 95% CI, 1.0–5.0) and to have lived with persons diagnosed with HCV infection (mOR, 3.0; 95% CI, 1.1–7.9). In a multivariate model, only outpatient endoscopy (adjusted OR, 10.8; 95% CI, 1.7–69.6) was significantly associated with case status. Conclusions: This is the first study to evaluate risk factors for acute HCV infection among adults in Ulaanbaatar, Mongolia. Outpatient endoscopy was associated with new HCV infections in this population; evaluation of gaps in infection control practices at settings providing these services are needed to prevent transmission of communicable diseases, including hepatitis C.Funding: NoneDisclosures: None

CDC issues guidance on exposure to HCV for health professionals

In late July, CDC released guidance on the testing and clinical management of health care personnel potentially exposed to hepatitis C virus (HCV). The agency noted that the incidence of acute HCV infections among patients is increasing in the United States as a result of risky behaviors such as injection drug use, placing providers at risk for HCV infections if exposed to the blood and other bodily fluids of infected patients. “Testing for occupational exposure for blood- or fluid-borne pathogens is standard practice for many years,” said Rima A. Mohammad, PharmD, FCCP, BCPS, clinical pharmacist specialist in general surgery/gastroenterology/nutrition at the University of Michigan. “This guideline outlines the steps to take specific to HCV occupational exposure, which is similar to any exposure to other blood- or fluid-borne pathogens. Baseline testing of the source patient and the health care provider should occur immediately, preferably within 48 hours of exposure. CDC notes that the source patient should be tested for HCV RNA using a nucleic acid test. However, for low-risk patients, screening for anti-HCV serology (i.e., antibodies) can be done as an alternative, followed by a nucleic acid test if the serology is positive. For providers, testing should include anti-HCV testing, and if positive, HCV RNA testing. If the HCV RNA is positive at baseline, then the provider is considered to have a preexisting HCV infection and should be referred for HCV treatment. If a patient is anti-HCV positive but HCV RNA negative, then follow-up testing for the provider is not required. However, if the patient is HCV RNA positive or if the RNA status of the patient is unknown, then the provider should have follow-up HCV RNA testing 3 to 6 weeks postexposure and a final anti-HCV test 4 to 6 months postexposure as there may be periods of aviremia during acute HCV infection. Postexposure prophylaxis for HCV is not recommended for health care providers who have occupational exposure to blood or other bodily fluids. It is estimated that only 0.2% of percutaneous exposures and 0% of mucocutaneous exposures result in HCV transmission. CDC recommends that curative antiviral regimens be reserved for treatment if confirmed HCV transmission occurs. “Compared to previous HCV treatments, HCV is much easier to treat with the newer therapies that are a shorter duration, [are] well tolerated, and have efficacy rates of more than 95% for a cure or sustained virologic response,” said Mohammad. “Therefore, we can delay HCV treatment until we confirm that the health care provider is positive for HCV. The key difference between hepatitis B virus (HBV) and HCV occupational exposure is that postexposure prophylaxis is recommended after HBV exposure in select situations. “Unfortunately, with other viruses, such as HBV, there is no ‘cure’ for the infection and health care providers may need to be on long-term treatment,” said Mohammad. “Therefore, it is important to treat providers with postexposure prophylaxis (if appropriate) as soon as we confirm that the patient has an HBV infection. Routine use of the HBV vaccination for health care providers, combined with standard precautions, has resulted in a 98% decline in HBV infections over the past 2 decades, according to CDC. For those who are exposed to HBV, CDC has specific recommendations based on the vaccination status of the provider, the anti-HBs levels of the provider (i.e., < or ≥10 mIU/mL), and the status of the source patient. Postexposure recommendations vary based on these factors, but administration of HBIG and the hepatitis B vaccines are listed as options. The HCV and HBV postexposure guidance documents are available on CDC's website. The new HCV information can be used to update procedures for postexposure testing and clinical management of providers potentially exposed to the virus.

Human defensins and Th-1 cytokines in hepatitis C viral infection.

Introductionactive or chronic exacerbated forms of hepatitis C virus (HCV) infection subsequently progress to liver disease and human defensins has been determined to have some level of anti-viral properties invitro whilst the expression of T helper-1 cytokines is known to promote complete recovery from acute HCV infection. The study sought to determine relationship between these immune responses.Methodsa cross sectional descriptive study design was employed. Hundred and thirty-two individuals were assessed were assessed for to anti-HCV, HCV RNA, serum levels of human alpha defensins 1 (HAD-1) and human beta defensins 1 (HBD-1). T helper 1 cytokines (IL-2, IFN gamma, TNF alpha) secreted in serum were also analyzed using commercial ELISA assay. The study was conducted in Kumasi, Obuasi and Daboya in Ghana.Resultsthe serum mean concentrations of HAD-1, HBD-1, IL-2, IFN gamma and TNF alpha showed no significant difference in concentrations among participants with chronic, spontaneously recovered or negative to HCV infection (p>0.05). Persons with hepatitis B co-infection were more likely to develop chronic HCV infection (p=0.039). HAD-1 and HBD-1 showed significant positive association with IL-2 (p=0.000) whilst only HAD-1 positively correlated with IL-2 (p<0.000).Conclusionthe immunological markers determined had no association with the status of HCV infection. HAD-1 increased with increasing levels of IL-2. These findings suggest that during HCV infection, inflammatory response through the production of cytokines by IL-2 cells may affect the release of HAD-1 and HBD-1.

Assessing County-Level Vulnerability for Opioid Overdose and Rapid Spread of Human Immunodeficiency Virus and Hepatitis C Infection in South Dakota.

Key indicators of vulnerability for the syndemic of opioid overdose, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) due to injection drug use (IDU) in rural reservation and frontier counties are unknown. We examined county-level vulnerability for this syndemic in South Dakota. Informed by prior methodology from the Centers for Disease Control and Prevention, we used acute and chronic HCV infections among persons aged ≤40 years as a proxy measure of IDU. Twenty-nine county-level indicators potentially associated with HCV infection rates were identified. Using these indicators, we examined relationships through bivariate and multivariate analysis and calculated a composite index score to identify the most vulnerable counties (top 20%) to this syndemic. Of the most vulnerable counties, 69% are reservation counties and 62% are rural. The county-level HCV infection rate is 4 times higher in minority counties than nonminority counties, and almost all significant indicators of opioid-related vulnerability in our analysis are structural and potentially modifiable through public health interventions and policies. Our assessment gives context to the magnitude of this syndemic in rural reservation and frontier counties and should inform the strategic allocation of prevention and intervention services.

Changes in circulating follicular helper T cells in peripheral blood of patients with acute hepatitis C virus infection.

To investigate the changes in circulating follicular helper T cells (cTfh) in peripheral blood of patients with acute hepatitis C virus (HCV) infection and its correlation with symptom severity of the disease. A total of 105 subjects were enrolled in this study, including 35 healthy people, 35 patients with acute HCV infection and 35 acute HCV patients with antiviral therapy. Flow cytometry was used to detect the expression of molecular markers related to the surface of cTfh cells, such as CD69, HLA-DR and CD57, and ELISA was used to detect the secretion of cytokines (IL-21, IL-4) in each group. The relationship between these markers and disease was analyzed statistically. Flow cytometry analysis demonstrated that the percentage of CD69 in peripheral blood of patients with acute hepatitis C infection was (18.90%±9.29%) significantly higher than that of normal control group (5.10%±4.21%) and antiviral treatment group (11.50%±5.38%). The difference was statistically significant (P<0.05). The results of HLA-DR and CD57 were consistent with CD69. The serum levels of IL-4 and IL-21 in the acute HCV infection group were significantly higher than those in the treatment and the control groups. After antiviral treatment, IL-4 and IL-21 levels significantly decreased but remained higher than those in the control group. This showed that antiviral treatment was effective, and the difference was statistically significant (P<0.05). The ratio of cTfh in infected group was negatively correlated with HCV RNA content (r=-0.6858, P=0.0028). Antiviral immune response in patients with acute hepatitis C infection may be related to the proportion of T helper cells in peripheral blood circulation follicles. Dynamic detection of the number of T helper cells in clinical practice is conducive to identifying more effective methods to treat acute hepatitis C infection, which has important theoretical and clinical significance.

Hepatitis C and hepatitis C-related advanced liver disease hospitalisation trends before and after the Strategic Plan for Tackling Hepatitis C in the National Health System.

This work evaluates the burden and trends of hepatitis C virus (HCV)-associated hospitalisations in Spain before and after the implementation of the Strategic Plan for Tackling Hepatitis C in the National Health System in 2015. HCV-related hospitalisation discharges from 2005 to 2017 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalisations was performed. From 2005 to 2017, there were 674 067 HCV-related hospitalisations: 1.2%, 29.9%, 63.9% and 5% of them due to acute, carriers, chronic and unspecified hepatitis C. Average age of the patients was 57.7 years (SD: 16.4), average hospital stay was 9.1 days (SD: 12.2) and intra-hospital case-fatality rate was 6.5%. Hospitalisation rates decreased notably (P < 0.05) in 2016-2017 compared to 2005-2015 for all [hospitalisation rate ratio (HRR): 0.77], males (HRR: 0.80), females (HRR: 0.74), chronic hepatitis C (HRR: 0.84), non-advanced liver disease (N-AdLD) (HRR: 0.80) and AdLD (HRR: 0.73). Acute HCV (HRR: 0.54) and carriers (HRR: 0.49) show decreases in 2016-2017 vs. 2005-2015, although their rates started to decrease in 2008/2009. Unspecified HCV hospitalisation rates increased (P < 0.05) in 2016-2017 (HRR: 2.02) vs. 2005-2015. From 2015 to 2017, cost per patient increased from 5981 euros to 6349 euros, but overall cost decreased, as hospitalisations rates decreased from 302 to 264 million euros. HCV-related hospitalisation rates decreased notably in 2016 and 2017 after the strategic plan for tackling hepatitis C was launched. Although cost per AdLD patient increased in 2016 and 2017, globally costs were reduced around 35 million euros per year.

Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus - CDC Guidance, United States, 2020.

SummaryExposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be performed as soon as possible (preferably within 48 hours) after the exposure. A source patient refers to any person receiving health care services whose blood or other potentially infectious material is the source of the HCP’s exposure. Two options are recommended for testing the source patient. The first option is to test the source patient with a nucleic acid test (NAT) for HCV RNA. This option is preferred, particularly if the source patient is known or suspected to have recent behaviors that increase risk for HCV acquisition (e.g., injection drug use within the previous 4 months) or if risk cannot be reliably assessed. The second option is to test the source patient for antibodies to hepatitis C virus (anti-HCV), then if positive, test for HCV RNA. For HCP, baseline testing for anti-HCV with reflex to a NAT for HCV RNA if positive should be conducted as soon as possible (preferably within 48 hours) after the exposure and may be simultaneous with source-patient testing. If follow-up testing is recommended based on the source patient’s status (e.g., HCV RNA positive or anti-HCV positive with unavailable HCV RNA or if the HCV infection status is unknown), HCP should be tested with a NAT for HCV RNA at 3–6 weeks postexposure. If HCV RNA is negative at 3–6 weeks postexposure, a final test for anti-HCV at 4–6 months postexposure is recommended. A source patient or HCP found to be positive for HCV RNA should be referred to care. Postexposure prophylaxis of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids. This guidance was developed based on expert opinion (CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommend Rep 2001;50[No. RR-11]; Supplementary Figure, https://stacks.cdc.gov/view/cdc/90288) and reflects updated guidance from professional organizations that recommend treatment for acute HCV infection. Health care providers can use this guidance to update their procedures for postexposure testing and clinical management of HCP potentially exposed to hepatitis C virus.

Role of tissue C4d in differentiation between acute rejection and HCV recurrence after living donor liver transplantation

Background: Liver biopsy represents the gold standard for diagnosis of acute rejection and HCV recurrence after liver transplantation; never the less discrimination can be difficult due to similar display of alterations in liver specimen. Therefore, a specific marker expressed only in rejection but not in HCV recurrence would be a great asset to differentiate between both conditions. The aim of this study was to assess the role of tissue C4d complement fragments in liver biopsy as a marker for differentiating between acute rejection and HCV recurrence in recipients post LDLT.Methods: A case control study on 25 recipients after liver transplantation with the suspicion of either acute rejection or HCV disease recurrence, patients were classified according to pathological finding into two groups, Group 1: patients with acute rejection (n=13), Group 2: patients with HCV recurrence (n=12), The C4d was evaluated by immunohistochemical staining of the formalin-fixed, paraffin-embedded tissue in different liver compartments.Results: C4D staining of all the studied tissue compartments (Sinusoids, portal vein endothelium, hepatic vein endothelium, arterial internal elastic lining, portal stroma, bile ducts) had high specificity (100%) and positive predictive value (100%) in diagnosis of rejection cases except portal vein endothelium. (Specificity 91.7%, positive predictive value 88.9%).Conclusions: Tissue C4d staining was almost present in rejection cases only; further studies on larger cohort are required to stand on standard diagnostic criteria for C4d to be included in diagnosis of acute rejection after liver transplantation as its role in other organ transplantation.

Recently acquired and early chronic hepatitis C in MSM: Recommendations from the European treatment network for HIV, hepatitis and global infectious diseases consensus panel.

: In response to growing evidence of an expanding epidemic of sexually acquired hepatitis C virus (HCV) infection in HIV-positive MSM, the European AIDS Treatment Network (NEAT) acute hepatitis C consensus panel developed their first recommendations for HCV prevention and care during a consensus conference in May 2010 in Paris, France. As then, two major breakthroughs have changed the landscape. First, directly acting antivirals (DAA) with high levels of tolerability and HCV cure rates of over 95% are now widely available and will play a large role in the goal of elimination of HCV by 2030 (WHO sector strategy). Second, landmark studies demonstrated that universal test and treatment (UTT) approach as well as the demonstration that HIV cannot be sexually transmitted from a person living with HIV with an undetectable viraemia [undetectable = untransmittable (U = U) campaign] and HIV preexposure prophylaxis (PrEP) are very effective HIV biomedical prevention strategies for MSM. The scale-up of these interventions has reduced HIV incidence in MSM and also changed patterns of sexual networks and behaviour, which has contributed to increased HCV incidence among HIV-negative MSM who were eligible for or on PrEP. These recent developments, together with new clinical and scientific insights, underscore the importance of updating the statements and recommendations for acute HCV in both HIV-positive and HIV-negative MSM. In June 2019, experts from different disciplines and organizations including community representatives participated at the second acute HCV consensus conference of NEAT Infectious Diseases (ID) in Amsterdam, the Netherlands.

Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing.

The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (seronegative) or early HCV infections. Seven of eight men reported condomless receptive anal intercourse (CRAI), six with rectal exposure to semen, and all eight denied rectal trauma or bleeding. Of the 10 HCV infections, eight resulted from transmission of a single virus; one infection resulted from transmission of either one or a few (three or four) closely-related viruses; and one infection resulted from transmission of >10 distinct viruses. The participant infected by >10 viruses reported sharing injection equipment for methamphetamine during sex. Two other participants also injected methamphetamine during sex but they did not share injection equipment and were infected by a single virus. Conclusions: Most HCV infections of HIV-infected MSM without a history of either rectal trauma or bleeding or shared injection equipment were caused by a single virus. Intra-rectal exposure to semen during CRAI is therefore likely sufficient for HCV transmission among MSM. Conversely, rectal trauma or bleeding or shared injection equipment are not necessary for HCV transmission among MSM. These results help clarify routes of HCV transmission among MSM and can therefore help guide the design of much-needed behavioral and other interventions to prevent HCV transmission among MSM.

Etiologies and Features of Acute Viral Hepatitis in Spain

Etiologies of acute viral hepatitis in high-income countries change with migration of populations, lifestyle changes, and emergence of new pathogens. We analyzed etiologies, characteristics, and outcomes of patients with acute viral hepatitis at a tertiary hospital in Spain. We analyzed data from all patients with acute hepatitis (n= 100; 71% male; median age, 42 years; 72% Spanish nationals), older than 16 years, diagnosed in the emergency department of an academic hospital in Barcelona, Spain, from January 2014 through December 2018. Blood samples were collected and patients with serum levels of alanine aminotransferase more than 10-fold the upper limit of normal and markers viral infection were considered to have acute viral hepatitis. We collected clinical information from patients, and samples were analyzed for IgM antibody to hepatitis B (HB) core antigen, HB surface antigen, antibody against hepatitis C virus (HCV), HCV RNA, IgM against hepatitis E virus (HEV), HEV RNA, and IgM against hepatitis A virus (HAV). Patients were followed until resolution of infections or evidence of chronic infection. The most common etiologies of acute hepatitis were HBV infection (28%), HEV infection (18%), HCV infection (17%), and HAV infection (14%). The main risk factors of the cohort were sexual risk contact and intravenous drug use; 79% of cases of HAV had sexual risk behavior. Twenty-nine percent of patients with acute HAV infection and 29% of patients with HBV infection were immigrants to Spain. Fifty-four patients were hospitalized; jaundice and HCV infection were associated with hospital admission. Three patients died (2 from acute liver failure related to acute HBV infection or HBV and HDV co-infection). Chronic infections developed in 5/28 patients (18%) with acute HBV infection and 7/17 patients (41%) with acute HCV infection. Despite universal vaccination against HBV in Spain, HBV remains the most frequent cause of acute viral hepatitis in our emergency department. Almost one-third of cases of acute HBV and HAV infections were immigrants, possibly from countries with suboptimal vaccination programs. A high proportion of patients with acute hepatitis have HEV infection (18%); acute HAV infection was associated with sexual risk behavior.

Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper.

In 1989, a collaboration between the Centers for Disease Control (CDC) and a California biotechnology company identified the hepatitis C virus (HCV, formerly known as non-A, non-B hepatitis virus) as the causative agent in the epidemic of silent posttransfusion hepatitis resulting in cirrhosis. We now know that, the HCV genome is a 9.6 kb positive, single-stranded RNA. A single open reading frame encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield 10 individual gene products, consisting of 3 structural proteins (core and envelope glycoproteins E1 and E2) and 7 nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which participate in posttranslational proteolytic processing and replication of HCV genetic material. Less than 25 years later, a new class of medications, known as direct-acting antivirals (DAAs) which target these proteins, were introduced to treat HCV infection. These highly effective antiviral agents are now approved for use in children as young as 3 years of age and have demonstrated sustained virologic responses exceeding 90% in most genotypes. Although tremendous scientific progress has been made, the incidence of acute HCV infections has increased by 4-fold since 2005, compounded in the last decade by a surge in opioid and intravenous drug use. Unfortunately, awareness of this deadly hepatotropic virus among members of the lay public remains limited. Patient education, advocacy, and counseling must, therefore, complement the availability of curative treatments against HCV infection if this virus is to be eradicated.

Trends in Indicators of Injection Drug Use, Indian Health Service, 2010-2014 : A Study of Health Care Encounter Data.

Hepatitis C virus (HCV) and HIV transmission in the United States may increase as a result of increasing rates of opioid use disorder (OUD) and associated injection drug use (IDU). Epidemiologic trends among American Indian/Alaska Native (AI/AN) persons are not well known. We analyzed 2010-2014 Indian Health Service data on health care encounters to assess regional and temporal trends in IDU indicators among adults aged ≥18 years. IDU indicators included acute or chronic HCV infection (only among adults aged 18-35 years), arm cellulitis and abscess, OUD, and opioid-related overdose. We calculated rates per 10 000 AI/AN adults for each IDU indicator overall and stratified by sex, age group, and region and evaluated rate ratios and trends by using Poisson regression analysis. Rates of HCV infection among adults aged 18-35 increased 9.4% per year, and rates of OUD among all adults increased 13.3% per year from 2010 to 2014. The rate of HCV infection among young women was approximately 1.3 times that among young men. Rates of opioid-related overdose among adults aged <50 years were approximately 1.4 times the rates among adults aged ≥50 years. Among young adults with HCV infection, 25.6% had concurrent OUD. Among all adults with arm cellulitis and abscess, 5.6% had concurrent OUD. Rates of HCV infection and OUD increased significantly in the AI/AN population. Strengthened public health efforts could ensure that AI/AN communities can address increasing needs for culturally appropriate interventions, including comprehensive syringe services programs, medication-assisted treatment, and opioid-related overdose prevention and can meet the growing need for treatment of HCV infection.

Incidence of HCV Reinfection Among HIV-Positive MSM and Its Association With Sexual Risk Behavior: A Longitudinal Analysis.

Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed. Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection. In total, 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range [IQR] 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (IQR 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3. Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.

Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy without antiviral prophylaxis.

No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n=306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P=.003) than those without HCV infection (n=4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P<.001 and P=.004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.

Abstract IA16: Prevention of hepatocellular carcinoma through preventative hepatitis C vaccination

Abstract In the United States, the incidence of hepatocellular carcinoma (HCC) has tripled and mortality rates have doubled since 1980. Between 2006 and 2015, HCC diagnoses increased by approximately 3% annually. Liver cancer is the fifth most common cause of cancer death in men and the seventh among women. Hepatitis C virus (HCV) infection is the primary risk factor for about one-third of cases of HCC in the US population. Hepatitis C virus (HCV) infection is a bloodborne disease with global distribution that affects almost 3% of the world’s population. Less than 20% of acute HCV infections cause acute viral hepatitis symptoms severe enough for the patient to seek medical care, and approximately 75% of all infections become persistent. Individuals with chronic HCV infection usually remain asymptomatic and undiagnosed for decades before chronic hepatitis leads to complications that can include severe fibrosis and cirrhosis, hepatic failure, or HCC. In studies of people with HCV, the risk for HCC increased as much as 3% per year after diagnosis of cirrhosis. Despite effective therapy, HCV remains the leading cause of liver failure requiring transplantation and HCC in many countries. Continuing advances in therapeutic regimens are promising for effecting cures of HCV and may reduce transmission. However, there remain challenges in HCV control. Identifying those with HCV infection is difficult because of its relative silence until end-stage disease develops. It is estimated that fewer than 5% of HCV-infected persons are diagnosed worldwide, and the proportion of patients who access and complete treatment remains low. Even when current HCV therapy is administered successfully, it does not provide immunity against subsequent infection. Intravenous drug users and other high-risk groups, such as health care providers, those living in endemic regions, and HIV-infected men who have sex with men, are at risk for new infections and will continue to be at increased risk of infection despite better regimens for HCV treatment. HCV transmission is likely to persist in areas with limited access to antiviral drugs and poor needle injection and blood product hygiene. These challenges, as well as the cost of therapy, make HCV therapy alone unlikely to block the spread of infection within the total human population and to eradicate HCV. In contrast, in Taiwan immunization of infants against hepatitis B virus (HBV) has substantially reduced HBV transmission and subsequently the risk of developing HCC as children and young adults. Therefore, development of a vaccine to prevent chronic HCV infection, if not to prevent infection altogether, remains a critical aspect of an HCV disease control platform. This talk will discuss the need for a vaccine, the evidence that a vaccine to prevent chronic infection is possible, and the vaccine strategies tested to date. Citation Format: Andrea L. Cox. Prevention of hepatocellular carcinoma through preventative hepatitis C vaccination [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA16.