Hepatitis C Virus Liver Research Articles

Prevalence of Hepatitis C in Liver Cirrhosis Patients

Background: Hepatitis C Virus (HCV) is a major cause of chronic liver disease, including liver cirrhosis, globally. Identifying the prevalence of HCV among cirrhotic patients can improve clinical outcomes and guide management strategies.Objective: To determine the prevalence of HCV in patients with liver cirrhosis and assess the association between liver enzyme levels (ALT and AST) and HCV infection.Methods: This retrospective observational study was conducted at Fatima Memorial Hospital, Lahore, from June 2023 to December 2023. Fifty liver cirrhosis patients with abnormal liver function tests were included. HCV infection was evaluated using ELISA for antibodies and PCR for RNA detection. Data analysis was performed using IBM SPSS version 25.0, with a p-value of <0.05 considered significant.Results: Among 50 cirrhotic patients, 60% tested positive for HCV antibodies via ELISA, and 46% were confirmed positive by PCR. Mean ALT levels were significantly higher in ELISA-positive (867 U/L) and PCR-positive (1096.43 U/L) patients compared to ELISA-negative (42 U/L) and PCR-negative (59.96 U/L) patients (p < 0.001).Conclusion: A significant prevalence of HCV was observed among liver cirrhosis patients, with elevated ALT and AST levels indicating liver damage associated with HCV infection.

Changing Epidemiology of Chronic Hepatitis C: A University Hospital Experience

Background: Hepatitis C virus (HCV) infection remains a significant public health problem worldwide, with varying epidemiological trends over time necessitating continual surveillance and intervention strategies. Objectives: This retrospective study aimed to examine trends in demographics, transmission routes, and disease characteristics among 635 patients diagnosed with HCV infection between 2003 and 2023. Methods: Data on demographics, HCV RNA levels, liver enzymes, genotype distribution, and transmission routes were retrospectively analyzed. The study period was divided into four segments for detailed analysis. Results: There was a gradual increase in the diagnosed cases over the study period, particularly noticeable after 2012. The mean age at diagnosis remained stable from 2003 - 2007 to 2008 - 2012 but decreased significantly in the following years (P = 0.001). Male predominance was observed throughout the study, with a notable increase in the male/female ratio over time (P < 0.001). Intravenous drug use (IVDU) emerged as the predominant transmission route, reaching 68.3% in 2018 - 2022 (P < 0.001). The prevalence of incarceration history among patients increased significantly, reaching 24.6% in 2018 - 2022 (P < 0.001). Disease characteristics varied between periods; median HCV RNA levels were highest in 2018 - 2022, and median alanine aminotransferase (ALT) levels differed significantly between periods (P = 0.001). The genotype distribution showed a shift over time, with genotype 1 predominating initially and genotypes 3, 4, and 5 becoming more prevalent in later years (P < 0.001). Conclusions: This study highlights the dynamic changes in hepatitis C epidemiology over two decades in southern Turkey, highlighting the increasing burden in younger populations, the increasing prevalence of IVDU as a transmission route, and the changing genotype distribution.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

Direct-Acting Antiviral Treatment for Acute Hepatitis C in Japanese Patients: Clinical Course and Outcomes.

We diagnosed six cases of acute hepatitis C virus (HCV) infection at our hospital between October 2003 and December 2022. During the same period, we diagnosed 402 cases of chronic HCV infection and 636 cases of acute hepatic injury. Acute HCV infection cases accounted for 1.4% of all HCV infections and 0.9% of all acute hepatic injury cases. The acute HCV infection group was younger, had more severe hepatitis, and exhibited higher levels of bilirubinemia compared to the chronic HCV infection group. Two acute HCV infection cases achieved spontaneous viral clearance, while the remaining four cases progressed to chronic infection and were treated with direct-acting antivirals (DAAs). Liver enzyme elevation and liver function deterioration did not differ significantly between the acute HCV and other acute liver injury groups. Notably, DAA treatment was equally effective for acute and chronic HCV cases (75% vs. 90%, p = 0.34). Early DAA treatment in acute cases might contribute to interrupting viral transmission among high-risk populations, such as people who inject drugsor men who have sex with men. While there are currently no specific guidelines for acute HCV infection treatment in Japan, our findings suggest that DAA therapy should be initiated immediately following diagnosis. Further studies with larger patient cohorts are warranted to confirm these observations.

Cosa deve sapere oggi il pediatra del trattamento dell’epatite C nell’era dei nuovi farmaci antivirali?

The treatment of hepatitis C virus (HCV) infection with the new directacting antivirals (DAAs) has dramatically modified the natural history of the HCV-related disease, eradicating the virus in over 90% of treated patients, with negligible collateral effects. The high costs of treatment, however, represent a factor that limits patients’ access to therapy and burdens the countries’ healthcare systems. In Italy the estimated cost of treatment for a naïve patient (8/12 weeks) amounts to approximately €5,500 (VAT excluded). HCV liver disease especially affects adults, in Italy the average prevalence of hepatitis C ranges between 2.4% and 3.3% in the general population. The prevalence of hepatitis C in children is significantly lower (0.15%) and the liver disease is rarely progressive in the paediatric age; however, there are not tools capable of interrupting the main route of infection, namely the vertical transmission from the infected mother. The effectiveness and great manageability of these new direct antivirals have also allowed their use in paediatrics starting from three years of age.

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

Serum microRNA-16 as a potential biomarker for HCV-induced hepato-cellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80–90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.

Serum omentin-1 is correlated with the severity of liver disease in patients with chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection have increased serum omentin-1. Omentin-1 is an anti-inflammatory adipokine, and higher levels may be a direct effect of HCV infection. Successful elimination of HCV by direct acting antivirals almost normalized circulating levels of various molecules with a role in inflammation. To evaluate the effect of HCV infection on serum omentin-1, serum omentin-1 levels of HCV patients were measured before therapy and at 12 wk after therapy end. Associations of serum omentin-1 with parameters of inflammation and liver function were explored at both time points. Serum omentin-1 levels of patients with and without liver cirrhosis, which was defined by ultrasound or the fibrosis-4 (FIB-4) score, were compared. Serum omentin-1 levels were measured by enzyme-linked immunosorbent assay in 84 chronic HCV patients before therapy and at 12 wk after therapy end where sustained virological response 12 (SVR12) was achieved in all patients. Serum omentin-1 of 14 non-infected controls was measured in parallel. In patients with chronic HCV, serum omentin-1 levels were not related to viral load or viral genotype. HCV patients with liver steatosis and HCV patients with diabetes had serum omentin-1 levels comparable to patients not suffering from these conditions. Serum omentin-1 levels at SVR12 were similar in comparison to pretreatment levels. In addition, serum levels did not differ between HCV-infected patients and non-infected controls. Serum omentin-1 levels did not correlate with leukocyte count or C-reactive protein. Positive correlations of serum omentin-1 with bilirubin and the model for end-stage liver disease score (MELD) were detected before therapy and at SVR12 in the whole cohort. Bilirubin and the MELD score also positively correlated with serum omentin-1 levels in the subgroup of patients with ultrasound diagnosed liver cirrhosis before therapy. At SVR12, serum omentin-1 levels of patients with liver cirrhosis negatively correlated with albumin. Before therapy start, patients with high FIB-4 scores had increased serum omentin-1 in comparison to patients with a low score. Serum omentin-1 levels of patients with liver cirrhosis defined by ultrasound were increased at baseline and at SVR12. Present study showed that liver cirrhosis, but not HCV infection per se, is related to elevated serum omentin-1 levels.

Mortality related to HCV and other chronic liver diseases in Veneto (Italy), 2008-2021: Changes in trends and age-period-cohort effects.

The objective of this study was to assess the impact of the COVID-19 pandemic and direct-acting antiviral (DAA) agents on mortality related to chronic liver diseases (CLD). Age-standardized mortality rates were computed based on CLD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple causes of death-MCOD). Time trends in age-standardized mortality rates were investigated using generalized estimation equation models. Additionally, we conducted age, period, and birth cohort (APC) analyses on CLD-related mortality associated with alcohol and hepatitis C virus (HCV). Between 2008 and 2021, among residents in the Veneto region (Northeastern Italy) aged ≥35 years, there were 20 409 deaths based on the UCOD and 30 069 deaths based on MCOD from all CLD. We observed a 4% annual decline in age-standardized MCOD-based mortality throughout 2008-2021, with minor peaks corresponding to COVID-19 epidemic waves. Starting in 2016, the decline in HCV-related mortality accelerated further (p < .001). A peak in HCV-related mortality in the 1963-1967 birth cohort was observed, which levelled off by the end of the study period. Mortality related to alcoholic liver disease declined at a slower pace, becoming the most common aetiology mentioned in death certificates. The study demonstrates a significant decrease in HCV-related mortality at the population level in Italy with the introduction of DAAs. Continuous monitoring of MCOD data is warranted to determine if this favourable trend will continue. Further studies utilizing additional health records are needed to clarify the role of other CLD etiologies.

Health-Related Quality of Life of People Who Inject Drugs: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study

ObjectivesThere is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We evaluated the HRQoL and associated factors among a cohort of PWID in Australia. MethodsParticipants were enrolled in an observational cohort study (the Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study) from May 2018 to September 2019 (wave 1) and November 2019 to June 2021 (wave 2). Participants completed the EQ-5D-5L survey at enrolment. Two-part models were used to assess the association of clinical and socioeconomic characteristics with EQ-5D-5L scores. ResultsAmong 2395 participants (median age, 43 years; 66% male), 65% reported injecting drug use in the past month, 20% had current hepatitis C virus (HCV) infection, and 68% had no/mild liver fibrosis (F0/F1). Overall, the mean EQ-5D-5L and EQ-visual analog scale scores were 0.78 and 57, respectively. In adjusted analysis, factors associated with significantly lower EQ-5D-5L scores include older ages, female (marginal effect = −0.03, P = .014), being homeless (marginal effect = −0.04, P = .040), and polysubstance use (marginal effect = −0.05, P < .001). Factors associated with significantly higher EQ-5D-5L scores were being Aboriginal/Torres Strait Islander (marginal effect = 0.03, P = .021) and recent injecting drug use in the past 12 months. Current HCV infection and liver fibrosis stage were not associated with reduced HRQoL among the study participants. ConclusionsPWID experienced a lower HRQoL compared with the general population. Further research is needed to understand HRQoL in this population to facilitate the development of multifaceted care models for PWID beyond HCV cure and inform health economic analyses for identifying optimal health strategies for PWID.

Non-invasive candidate proteinsignature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response.

A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy.

The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.

A cross-sectional study on co-infection of hepatitis B and hepatitis C among people living with HIV/AIDS from a tertiary care hospital of Central India

Background: Hepatitis B virus (HBV), hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) infections are prevalent throughout the world. HIV infection increases the risk of HBV and HCV liver disease especially when HIV-associated immunodeficiency progresses. Aims and Objectives: This study was carried out with the objectives as follows: Estimation of the prevalence of HIV- Hepatitis co-infection, determine CD4+T lymphocyte count in co-infected patients, identify most common opportunistic infections in HIV – Hepatitis co- infection. Materials and Methods: A hospital-based, prospective, cross-sectional, and observational study was carried among people with confirmed HIV infection. HIV antibody, hepatitis B surface antigen (HBsAg), and HCV antibody tests were done in all patients visiting to integrated counseling and testing center. HIV, HBV, and HCV viral load were done in all serologically confirmed patients. In HBsAg positive patients various markers for hepatitis such as hepatitis B envelop antigen (HBeAg), anti-hepatitis B core antibody (HBcAb), and anti-hepatitis B envelop antibody were also done. Results: Out of 357 people living with HIV/AIDS (PLHA) patients 15/357 (4.20%) were co-infected with HBV, 03/357 (0.84%) were co-infected with HCV. The overall seroprevalence of Hepatitis virus (HBV+HCV) in PLHA patients was found to be 5.04% (18/357). CD4+T lymphocyte count &lt;200 cells/μL was seen in 66/339 (19.4%), 04/15 (26.6%), and 03/03 (100%) patients of HIV mono-infected, HBV co-infected, and in HCV co-infected patients, respectively. HIV Viral load ≤1000 copies/mL was seen in 324 and 15 patients in HIV mono-infected and HIV- hepatitis co-infected patient, respectively. Among PLHA patients who were positive for HBsAg; 46.7% (n=7) patients had HBV viral load &gt;2000 IU/mL. All hepatitis B co-infected patients were positive for HBcAb test; HBeAg was positive in 40% (n=06). All HBeAg positive were having viral load &gt;2000 IU/mL. Conclusion: HIV-infected patients are more prone to hepatitis associated liver diseases and exposure to the HBV infection than the general population.

Child-Pugh Class B or C Liver Disease Increases the Risk of Early Mortality in Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty Regardless of Treatment Status.

Patients with hepatitis C virus (HCV) undergoing primary elective total joint arthroplasty (TJA) are at increased risk of postoperative complications. Patients with chronic liver disease and cirrhosis, specifically Child-Pugh Class B and C, who are undergoing general surgery have high 2-year mortality risks, approaching 60% to 80%. However, the role of Child-Pugh and Model for End-Stage Liver Disease classifications of liver status in predicting survivorship among patients with HCV undergoing elective arthroplasty has not been elucidated. What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty? We performed a retrospective study at three tertiary academic medical centers and identified patients with HCV undergoing primary elective TJA between January 2005 and December 2019. Patients who underwent revision TJA and simultaneous primary TJA were excluded. A total of 226 patients were eligible for inclusion in the study. A further 25% (57) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis. The mean follow-up duration was 53 ± 29 months. We compared confounding variables for mortality between patients with early mortality (16 patients) and surviving patients (153 patients), including comorbidities, HCV and liver characteristics, HCV treatment, and postoperative medical and surgical complications. Patients with early postoperative mortality were more likely to have an associated advanced Child-Pugh classification and comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease. However, both groups had similar 90-day and 1-year medical complication risks including myocardial infarction, stroke, pulmonary embolism, and reoperations for periprosthetic joint infection and mechanical failure. A multivariable regression analysis was performed to identify independent factors associated with early mortality, incorporating all significant variables with p < 0.05 present in the univariate analysis. After accounting for significant variables in the univariate analysis such as peripheral vascular disease, end-stage renal disease, heart failure, chronic obstructive pulmonary disease, and liver fibrosis staging, Child-Pugh Class B or C classification was found to be the sole factor independently associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001). The risk of early mortality in patients with Child-Pugh Class B or C was 64% (seven of 11) compared with 6% (nine of 158) in patients with Child-Pugh Class A (p < 0.001). Patients with HCV and a Child-Pugh Class B or C at the time of elective TJA had substantially increased odds of death, regardless of liver function, cirrhosis, age, Model for End-Stage Liver Disease level, HCV treatment, and viral load status. This is similar to the risk of early mortality observed in patients with chronic liver disease undergoing abdominal and cardiac surgery. Surgeons should avoid these major elective procedures in patients with Child-Pugh Class B or C whenever possible. For patients who feel their arthritic symptoms and pain are unbearable, surgeons need to be clear that the risk of death is considerably elevated. Level III, therapeutic study.

Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study.

In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

Longitudinal multi-omics analyses of the gut-liver axis reveals metabolic dysregulation in hepatitis C infection and cirrhosis.

The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear. Here we used multi-omics analysis of portal and peripheral blood, faeces and liver tissue to characterize the gut-liver axis of patients with HCV across a fibrosis severity gradient before (n = 29) and 6 months after (n = 23) sustained virologic response, that is, no detection of the virus. Fatty acids were the major metabolites perturbed across the liver, portal vein and gut microbiome in HCV, especially in patients with cirrhosis. Decreased fatty acid degradation by hepatic peroxisomes and mitochondria was coupled with increased free fatty acid (FFA) influx to the liver via the portal vein. Metatranscriptomics indicated that Anaerostipes hadrus-mediated fatty acid synthesis influences portal FFAs. Both microbial fatty acid synthesis and portal FFAs were associated with enhanced hepatic fibrosis. Bacteroides vulgatus-mediated intestinal glycan breakdown was linked to portal glycan products, which in turn correlated with enhanced portal inflammation in HCV. Paired comparison of patient samples at both timepoints showed that hepatic metabolism, especially in peroxisomes, is persistently dysregulated in cirrhosis independently of the virus. Sustained virologic response was associated with a potential beneficial role for Methanobrevibacter smithii, which correlated with liver disease severity markers. These results develop our understanding of the gut-liver axis in HCV and non-HCV liver disease aetiologies and provide a foundation for future therapies.

HCV elimination in a Swiss opioid agonist therapy programme – a cohort study

In opioid agonist therapy (OAT) programmes, chronic hepatitis C is highly prevalent and directly observed therapy guarantees optimal adherence. Since 2017, all patients with chronic hepatitis C in Switzerland can be treated with pangenotypic direct-acting antivirals irrespective of liver fibrosis stage. Until the end of 2021, however, prescription was restricted to infectious disease specialists, gastroenterologists and certain addiction specialists. Difficult venous access after long-term intravenous drug use and, in the case of referral to a specialist, difficulties keeping appointments are barriers to HCV diagnosis and treatment. To assess whether minimally invasive point-of-care tests and a "test-and-treat / vaccinate on-site" approach can improve human immunodeficiency virus (HIV) / hepatitis C virus (HCV) screening, HCV treatment uptake and immunity against hepatitis A/B. Since September 2018, an infectious disease specialist and a study nurse performed 4-weekly visits in the OAT programme "HAG" (heroin dispensation of the canton Aargau), offering HIV/HCV antibody rapid testing (20 min) and HCV RNA quantification (GeneXpert®, 60 min) from capillary blood, noninvasive liver fibrosis assessment (Fibroscan®, 5-10 min) and HCV treatment prescription on-site. Recommended venous blood draws for HAV/HBV serology and HAV/HBV vaccinations were performed by the staff of the "HAG". Project performance was assessed by annual cross-sectional chart review. Of the 128 patients registered in April 2018, 79 (62%) were still present in May 2021. With 72 newly registered, a total of 200 patients could be assessed, of whom 129 (65%) were still present in May 2021. Between April 2018 and May 2021, the proportion ever tested for HIV antibodies increased from 79% (101/128) to 91% (117/129), the proportion ever tested for HCV antibodies from 83% (106/128) to 93% (120/129) and the proportion of those HCV antibody positive ever tested for HCV RNA tested from 89% (47/53) to 98% (56/57). The proportion with adequate HCV management (last HCV antibody test ≤1 year ago, if HCV antibody negative or last HCV RNA test ≤1 year ago, if HCV antibody-positive and RNA-negative) improved from 23% ([15 + 15]/128) to 80% ([55 + 48]/129). Overall, HCV treatment uptake increased from 60% (21/35) to 92% (55/60) and HCV RNA prevalence among the HCV antibody positives decreased from 38% (18/47) to 7% (6/84). Between 2018 and 2021, 19 non-cirrhotic chronic hepatitis C patients were successfully treated on-site (18 sustained virological responses [SVR] 12, 1 SVR4), with excellent adherence (≥93%) and, so far, no reinfection. The proportion with known HAV/HBV serostatus increased from 38%/51% to 64%/76%. Immunity against HAV/HBV improved from 19%/23% to 50%/57%. Capillary blood point-of-care tests and a "test-and-treat / vaccinate on-site" approach remove crucial barriers to diagnosis and treatment, making hepatitis elimination in OAT programmes achievable. A high fluctuation rate requires HIV/HCV/HAV/HBV testing at admission, but also allows more patients to be screened.

HCV Infection and Liver Cirrhosis Are Associated with a Less-Favorable Serum Cholesteryl Ester Profile Which Improves through the Successful Treatment of HCV.

Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.

Monitoring the progress towards the elimination of hepatitis B and C in Sweden: estimation of core indicators for 2015 and 2018

IntroductionTo monitor Sweden’s progress towards the WHO goal of eliminating viral hepatitis, we estimated the prevalence, notification rate, and liver-related morbidity and mortality for diagnosed hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 2015 and 2018.MethodsWe identified cases of hepatitis B and C within the National System for Notifiable Diseases and obtained data on treatment and whether the case was deceased or not. We calculated prevalence, notification rates per 100,000, and proportion of newly diagnosed cases of hepatitis with liver disease at the time of diagnosis, and proportion of all deceased cases who died from liver disease. We calculated Poisson 95% confidence intervals (CIs) around the notification rates and Wilson 95% CIs around prevalence and mortality estimates.ResultsIn 2015 and 2018, the prevalence of diagnosed HBV infections was 0.20% [95% CI: 0.19–0.20] and 0.21% [0.20–0.21]. Notification rates per 100,000 for HBV infections were 13.02 [12.32–13.76] and 7.71 [7.18–8.27]. HBV liver-related morbidity was 2.65% [1.90–3.68] and 2.16% [1.35–3.43]. HBV liver-related mortality was 20.00% [14.81–26.44] and 17.95% [13.20–23.94]. In 2015 and 2018, the prevalence of diagnosed HCV-infections was 0.24% [0.24–0.25] and 0.18% [0.18–0.19]. Notification rates per 100,000 for HCV infections were 15.92 [15.14–16.73] and 13.05 [12.36–13.77]. HCV liver–related morbidity was 8.14% [6.89–9.60] and 3.90% [2.99–5.08]. HCV liver–related mortality was 27.08% [24.54–29.77] and 26.90% [24.12–29.88].ConclusionsAll indicators decreased or remained stable between 2015 and 2018, indicating progress in the elimination of viral hepatitis, especially for HCV infection.

Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma.

The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.