Eradication Of Hepatitis Research Articles

Primary healthcare as a strategy for eliminating hepatitis C: the METRIC toolkit.

This paper presents the development of the METRIC toolkit, aimed at enhancing primary healthcare interventions in the context of hepatitis C control, thus contributing to the World Health Organization's global strategy to achieve the elimination of the disease by 2030. At the global level, most people living with hepatitis C are unaware of their condition. As such, the eradication of hepatitis C necessitates comprehensive strategies within primary healthcare settings, as it provides an opportunity to reach the general population, facilitates the identification of potential patients who may be unfamiliar with hepatitis C, and guides them toward adequate care. Herein, we propose the METRIC toolkit as a means to optimize the efficiency and efficacy of healthcare services dedicated to hepatitis C control. The development of the METRIC toolkit was guided by a thorough review of pertinent literature, focusing on primary healthcare interventions in hepatitis C control. Key components were identified, encompassing systematic problem identification, solution formulation, outcome evaluation, and feedback integration. The METRIC toolkit represents a valuable resource for strengthening primary healthcare interventions in hepatitis C control. By fostering a culture of continuous improvement and data-driven decision-making, this framework holds promise in advancing the global agenda towards hepatitis C elimination. However, its successful application requires careful consideration of contextual factors and ongoing adaptation to local needs and circumstances.

CHRONIC HEPATITIS B VIRUS INFECTION: SYSTEMATIC REVIEW OF EPIDEMIOLOGY, MECHANISMS OF VIRAL PERSISTENCE AND TREATMENT OF THE CONDITION

Objective: The general objective of this study is to analyze the scientific production on chronic infection by the Hepatitis B virus, seeking to identify the main methods used in the treatment of this pathology. Methodology: This is a systematic review focused on understanding the main aspects that permeate chronic infection by the Hepatitis B virus. The research was guided by the question: “What are the main aspects that permeate chronic infection by the Hepatitis B virus, as well as what are the diagnostic and therapeutic resources used in clinical practice?”. To find answers, searches were performed in the PubMed database using five descriptors combined with the Boolean term “AND”. This resulted in 408 articles. Twenty-four articles were selected for analysis and 15 articles were used to compose the collection. Results: The eradication of hepatitis B depends on the combination of preventive and therapeutic efforts. The persistence of cccDNA in the liver, even after viral suppression, makes complete functional cure difficult. Antivirals such as entecavir and tenofovir are effective in reducing viral load, but they fail to eradicate the virus in most patients, requiring prolonged treatments. Furthermore, the variability in treatment responses, influenced by factors such as viral genotype and disease stage, highlights the need for personalized approaches to improve clinical management. In summary, despite advances, there are still important challenges to be addressed in the search for a cure for chronic hepatitis B. Conclusion: The systematic review highlighted the main aspects of chronic hepatitis B (CHB), emphasizing its challenges and advances in clinical management. Chronic hepatitis B virus (HBV) infection remains a serious public health problem, with complications such as liver cirrhosis and hepatocellular carcinoma. Prevention strategies, such as universal vaccination and immunoprophylaxis, are effective in reducing vertical transmission, especially in newborns, but global adherence still needs to improve, especially in areas of high prevalence.

Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment.

Achieving HBsAg loss is a critical clinical milestone in the management of chronic hepatitis B (CHB) towards the eradication of hepatitis B. However, there are limited researches on the incidence and determinants of HBsAg loss in paediatric CHB patients undergoing antiviral treatment. Therefore, we aimed to analyse the incidence and potential determinants of HBsAg loss in children who suffered from CHB and received antiviral treatment. This retrospective cohort study was performed on paediatric patients with progressive CHB who initiated either monotherapy or combination therapy using interferon/peg-interferon and entecavir. We utilised Cox regression models to evaluate the relationships between HBsAg loss and various determining factors. In total of 306 subjects with an average age of 4.99 years (range 1-15) were identified in this study, of whom 200 (65.4%) were male. After a median follow-up of 26 months, HBsAg loss occurred in 135 participants. The accumulated rate of HBsAg loss was 67.8% at the end of the follow-up evaluation. Multivariate Cox regression analysis revealed that older age (HR = 0.84, 95% CI: 0.79-0.90), female sex (HR = 1.61, 95% CI: 1.13-2.30), baseline HBsAg levels (HR = 0.72, 95% CI: 0.62-0.84), HBsAb positivity (HR = 1.77, 95% CI: 1.20-2.59) and serum bilirubin levels (HR = 0.96, 95% CI: 0.92-0.99) were statistically significant predictors of HBsAg loss. The incidence of HBsAg loss continues to increase in paediatric patients with CHB after antiviral treatment. Age, sex, baseline HBsAg and bilirubin levels and HBsAb positivity are found to be associated with sustained HBsAg loss.

Magnetic resonance spectroscopy as a diagnostic model for assessment of liver steatosis in metabolic dysfunction-associated steatotic liver disease in non-diabetic patients

BackgroundMetabolic dysfunction-associated steatotic liver (MASLD) disease is the commonest hepatic cause of liver fibrosis and cirrhosis after the introduction of the direct acting antivirals and eradication of hepatitis C. MASLD is usually associated with metabolic syndrome and elevated inflammatory markers. Magnetic resonance spectroscopy (MRS) offers a non-invasive diagnostic, alternative to liver biopsy. This is a case–control diagnostic-accuracy study conducted on 40 patients in the Hepato-gastroenterology Unit in the Internal Medicine Department, Ain Shams University Hospitals, to study the role of MRI spectroscopy as a new diagnostic model for assessment of liver steatosis in non-diabetic MASLD patients compared to the standard ultrasound and clinical criteria. MASLD was diagnosed by a combination of a validated ultrasound hepatic steatosis score grading system and hepatic steatosis index using clinical and laboratory parameters. MRS was performed in all patients and fat peak, water peak, and fat fraction % were measured, and diagnostic accuracy of different MRS is compared to the US scoring and different laboratory and clinical parameters. To our knowledge this is the first study conducted on MRS in our region and Egypt.ResultsThis study revealed no statistically significant difference between the two groups regarding HbA1C, creatinine, while there was highly statistically significant difference regarding fasting blood sugar, 2 h post-prandial glucose level, urine albumin, and low-density lipoprotein levels. Hepatic steatosis score grading by abdominal ultrasound on the 20 controls showed no fatty changes with grade 0 (50%), and on the 20 MASLD patients showed that 2 cases were grade 1 steatosis (5%), 9 cases were grade 2 steatosis (22.5%), and 9 cases were grade 3 steatosis (22.5%). The diagnostic accuracy of predicting hepatic steatosis using different MRS parameters: fat peak, water peak, and fat fraction had area under the curve of 99.9%, 88.6%, and 100%, respectively. The sensitivity and specificity of fat fraction in detecting hepatic steatosis were 100%. The sensitivity and specificity of the fat peak in detecting hepatic steatosis were 100% and 95%, respectively. Moreover, the sensitivity and specificity of the water peak in detecting the hepatic steatosis were 88.6% and 85%, respectively. There is a statistically significant correlation between the three MRS parameters and the abdominal ultrasound hepatic steatosis score grades.ConclusionMRS parameters: fat fraction, fat peak, and water peak, have high diagnostic accuracy for predicting the liver steatosis. Moreover, MRS has the added advantage of being a non-invasive and a tool with low radiation risk. MRS also shows the metabolic changes in the liver and could be an eligible outcome in therapeutic clinical trials.

An Update on Viral Hepatitis B and C in Mexico: Advances and Pitfalls in Eradication Strategies.

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections' elimination.

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals

Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Study of Risk Factors in Patient with Persistant Elevation of Liver Enzymes after Treatment of Chronic HCV by Direct Acting Antiviral Drugs (DAADs)

Abstract Background Hepatitis C virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide, with 3- 4 million new infections and 350000 deaths occurring each year because of HCV- related complications. Egypt is the country with the highest HCV prevalence in the world. Aim of the Work The aim of this study is to determine risk factors that cause persistent elevation of liver enzymes in hepatitis c virus patients treated by direct acting antiviral drugs (dyslipidemia, high BMI, type2 diabte, NAFLD). Patients and Methods This retrospective cross sectional study was conducted on 128 Egyptian candidates achieved SVR after 12 weeks with elevated liver enzymes before treatment by (DAAds) Results In this study, we found that there were correlations between the elevated ALT levels and most metabolic risk factors. There were increase in TG, BMI, and decreased. HDL-c, which were components of metabolic syndrome, were associated with high ALT levels in patients. Metabolic syndrome (MS) components are highly prevalent in NAFLD lack of biochemical response was associated with a higher risk to develop liver related complications (decompensation and cancer), indicating that these patients should undergo further hepatological followup. Conclusion Further large-scale studies employing larger number of patients are needed to evaluate risk factors that cause persistent elevated liver enzymes after eradication of hepatitis c viral infection with DAAds.

Changes in Components of Metabolic Syndrome after Antiviral Eradication in Hepatitis C Virus Infection.

Chronic hepatitis C infection is a systemic disease that affects over 71 million patients all over the world and it is to be considered nowadays as a new cardiometabolic risk factor. This study aimed to evaluate the weight and metabolic changes after viral eradication in patients with hepatitis C virus (HCV) infection. We conducted a prospective study between October 2017 to December 2021, in a tertiary care center, in which we included 132 patients with HCV or cirrhosis. All patients received treatment with direct antivirals (DAAs) and achieved sustained viral response at 12 weeks (SVR12). During the study, clinical laboratory data and Fibroscan examinations were recorded in all patients. The study group was evaluated at the initiation of antiviral treatment, at SVR12, and within an average follow-up period of 6 months to 12 months after the previous evaluation. Evaluation at SVR12 and the data recorded in the post-SVR surveillance period show a further increase in BMI compared with baseline measurements with a statistically significant difference (27.11 ± 3.22 vs. 27.415 ± 3.03 vs. 28.04 ± 1.11 kg/m2, p = 0.012). The same observation was noticed for waist circumference (WC) at post-SVR evaluation (87.6 ± 13.1 vs. 88.4 ± 13.6 cm, p = 0.031). Moreover, the study population registered an increase in the average total cholesterol (TC) values at post-SVR evaluation (177.01 ± 42.2 mg/dL, p = 0.014) compared to baseline. In addition, the serum level of triglycerides had been modified after viral clearance, with a minimal decrease in the mean values of triglycerides (TGD) at SVR-12 assessment (133.48 ± 41.8 mg/dL, p = 0.78), followed by a significant increase to the mean value of 145.4 ± 47.2 mg/dL (p = 0.026) in the third evaluation. Our study highlights that HCV eradication does not improve the lipid profile in the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, TGD, and weight gain.

No increased risk of hepatocellular carcinoma after eradication of hepatitis C virus by direct-acting antivirals, compared with interferon-based therapy

It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, n = 320) or Sim+IFN (000015933, n = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.

Impact of antiviral therapy for disease progression and non-invasive liver fibrosis index in patients with chronic hepatitis C: Markov chain model analysis.

Antiviral therapy advancements resulted in an era in which eradication of hepatitis C has become a goal, however, there are few reports on the long-term course of liver disease progression with antiviral therapy. The aim of this study was to use the Markov model to analyze disease progression and non-invasive liver fibrosis index in hepatitis C Patients. Patients with chronic hepatitis C (n=1432) were diagnosed between January 2012 and May 2021 in the Musashino Red Cross Hospital. Patients with other hepatitis virus co-infection, chronic liver disease, and hepatocellular carcinoma (HCC) at the beginning of the study were excluded. A total of 618 patients with a 1-year or longer observation period were studied. The liver disease state was defined as chronic hepatitis (CH), compensated liver cirrhosis (CLC), decompensated liver cirrhosis (DLC), and HCC. Cirrhosis and high FIB-4 index (≥3.61) were 42 cases (6.8%) and 208 cases (33.6%), respectively at the start of the study. The 40years estimated transition analysis of 40-year-old CH low FIB-4 level (<3.61) revealed that the proportion of CH low/high, CLC low/high, DLC low/high, and HCC were 10.83%/10.86%, 0.35%/2.64%, 0%/3.21% 72.11% in untreated unit and 47.83%/9.21%, 6.69%/1.32%, 0.70%/0.99%, 33.27% in treated unit, respectively. Antiviral therapy suppressed liver fibrosis, disease progression, and HCC development significantly. Markov model analysis of hepatitis C virus patients showed the impact of antiviral therapy on the suppression of disease progression in the order of CH, CLC, and DLC.

Successful Eradication of Hepatitis C Virus with Sofosbuvir based Antiviral treatment results in improvement in quality of life in cirrhotic patients

Hepatitis C virus (HCV) infection has long been a serious global public health concern; it is not only the main cause of end-stage liver disease, but it is also a leading source of liver cancer, but it also increases the risk of mortality from a variety of extrahepatic illnesses. Objective: The study's main objective is to see if successfully eradicating the Hepatitis-C virus with sofosbuvir-based antiviral therapy improves cirrhotic patients' quality of life. Methods: This cross-sectional study was conducted in Faisalabad Medical University from June 2019 to June 2020. The data was collected from 70 patients. The data was collected through a non-probability consecutive sampling technique. Results: The data were collected from 70 patients of both genders. We compared patients' quality of life. With sofosbuvir and ribavirin, 56 patients (79%) reached Sustained Virologic Response 12 (SVR12), Sofosbuvir, daclatasvir, and ribavirin were administered to 13 patients (18%), while sofosbuvir and ledipasvir were administered to two individuals (3%).Conclusions: Infection with chronic HCV, which is made worse by cirrhosis, has a major negative influence on the patient's physical, mental, social, and functional well-being, leading to a considerable reduction in their overall quality of life.

The Impact of Cirrhosis and History of Hepatocellular Carcinoma on All-Cause Mortality After Eradication of Hepatitis C Virus in Patients With Chronic Hepatitis C.

Cirrhosis and hepatocellular carcinoma (HCC) are potentially fatal complications of chronic hepatitis C virus (HCV) infection. We investigated how compensated cirrhosis and a history of curatively treated HCC influenced patient mortality after HCV eradication, that is, sustained virologic response (SVR). We studied 5458 patients with confirmed SVR who were prospectively followed up for more than 1 year after SVR achieved with direct-acting antivirals. Mortality and the incidence of HCC development after SVR were analyzed based on the presence or absence of compensated cirrhosis or a history of curatively treated HCC before the start of therapy. Mortality and the incidence of post-SVR HCC were significantly higher in patients with compensated cirrhosis and those with a history of curatively treated HCC than in those without these complications. Multivariate analysis showed that a history of HCC was associated with high mortality after SVR. In patients with no history of HCC, cirrhosis was associated with high mortality. Although both liver-related and nonliver-related mortality rates were significantly higher in patients with a history of HCC or cirrhosis, nonliver-related mortality did not differ based on HCC history, and liver-related and nonliver-related mortality were comparable regardless of cirrhosis after propensity score matching with age, gender, alcohol intake, and comorbidities. Mortality after SVR was significantly higher in patients with compensated cirrhosis or a history of HCC. While a history of HCC significantly increased mortality after SVR, even following curative treatment, the impact of pre-SVR compensated cirrhosis on post-SVR mortality was modest.

The Effect of HCV Eradication after Direct-Acting Antiviral Agents on Hepatic Steatosis: A Prospective Observational Study

Eradication of hepatitis C virus (HCV) by direct-acting-antiviral- agents (DAAs) was followed by fibrosis regression, but little is available about hepatic steatosis changes after DAAs. The aim of this work was to assess the prevalence of hepatic steatosis among HCV Egyptian patients and the long term changes occuring after viral eradication. This prospective cohort study included 150 HCV patients with significant fibrosis. They were examined by Transient elastography to evaluate liver stiffness measurement (LSM) and hepatic steatosis before treatment, at SVR12 and 1 year after the end of therapy. LSM showed a significant positive correlation to pretreatment of hepatic steatosis. LSM significantly decreased and hepatic steatosis significantly increased both at SVR12 and one year after DAAs. Patients with steatosis showed significantly higher median LSM and controlled attenuation parameter (CAP) values at: baseline, SVR12, and one year after therapy. Also, the pretreatment steatosis and body mass index (BMI) had a significant negative correlation with fibrosis regression one year after therapy in all studied groups. Hepatic steatosis is common in HCV Egyptian patients and increases after HCV eradication with DAAs. BMI and CAP values are negatively correlated to hepatic fibrosis regression and positively correlated to steatosis progression one year after DAAs. So, HCV patients with hepatic steatosis may need close follow up for atherosclerotic and HCC risk after DAAs, especially if they are overweight.

Liver stiffness-based score at sustained virologic response predicts liver-related complications after eradication of hepatitis C virus.

To determine whether liver stiffness (LS) and fibrosis-4 (Fib-4) index were useful in assessing the occurrence of liver-related complications (LRC) in chronic hepatitis C (CHC) patients after direct-acting antivirals (DAAs) had been administered. This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. A total of 697 (male/female: 294/403, mean age: 63.8year) patients with measured LS and complete lab data at SVR were enrolled, followed, and analyzed. In a median follow-up of 21.4months after SVR, 39 patients developed LRC including 28 with hepatocellular carcinoma (HCC), with the 30-month cumulative incidence of LRC and HCC being 7.7% and 5.1%, respectively. Predictions of occurrence of LRC and HCC were 0.820 and 0.774 for LS, and 0.775 and 0.737 for Fib-4, with optimal cutoffs of LS and Fib-4 being 14.5 kPa and 2.9 for LRC prediction. In multivariate analysis, LS was associated with the occurrence of LRC (hazard ratio: 3.97, 95% confidence interval [1.866, 8.446], p < 0.001) after adjustment for Fib-4 and diabetes. A risk-score system combining LS, Fib-4, and diabetes was developed for LRC risk assessment. Patients were stratified into low- (score 0-1), intermediate- (score 2-3), and high-risk (score 4) groups with LRC cumulative incidences of 1.7%, 14.9%, and 36.4%, respectively (p < 0.001). For patients with CHC after DAA, the risk scoring system based on LS, Fib-4, and diabetes was useful to assess the risk of LRC development during follow-up; accordingly, it would be advantageous for clinicians to set up more personalized and cost-effective strategies of surveillance.

Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum‐based risk model that could identify patients with low‐risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma‐glutamyl transferase < 28 IU/L, alpha‐fetoprotein < 4.0 ng/mL, and Fibrosis‐4 Index < 4.28) were classified as low‐risk and others were classified as high‐risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low‐risk patients (0.5‐1.1 per 100 person‐years in the derivation cohort and 0.9‐1.1 per 100 person‐years in the validation cohort) than in high‐risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high‐risk to low‐risk (HCC incidence: 0.6 per 100 person‐years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person‐years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.

Long-term persistence of hepatocarcinogenic potential of a non-hypervascular hypointense nodule on EOB-MRI after the eradication of hepatitis C virus.

Non-hypervascular hypointense nodules (NHHNs) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of hypervascularization progressing to typical hypervascular hepatocellular carcinoma (HCC). NHHNs that were present before the start of anti-hepatitis C virus (HCV) therapy is a risk marker for HCC development after achieving sustained virologic response (SVR). In this report, we show a patient without a previous history of HCC in whom HCC developed by hypervascularization of NHHN after SVR. This patient achieved SVR more than 8years before NHHN developed into HCC, and during this time NHHN had been present but had remained unchanged in size and imaging features as shown by repeated EOB-MRI. Hepatocarcinogenic potential of NHHNs persist for a long time after SVR, despite the eradication of HCV.

Effectiveness of direct acting antiviral agents for hepatitis C virus related recurrent hepatocellular carcinoma patients who had multiple courses of recurrence.

Eradication of hepatitis C virus (HCV) using direct acting antiviral agents (DAAs) has been reported to alter liver function and reduce the recurrence rate after curative treatment in naïve hepatocellular carcinoma (HCC) patients. However, it is not well known whether administration of DAAs had favourable effect on HCC patients with multiple courses of recurrence. We retrospectively extracted 146 HCV-related HCC (C-HCC) patients who received curative treatment using radiofrequency ablation (RFA) followed by eradication treatment with DAA between 1 January 2015 and 31 December 2017. We also extracted 184 C-HCC patients who were curatively treated using RFA without HCV eradication treatment between 1 January 2009 and 31 July 2014 as controls. We used propensity score matching method and adjusted following factors between the 2 groups: age, sex, liver function, number of recurrence times, tumour diameter and tumour numbers. We finally enrolled 47 C-HCC patients with eradication of HCV, and 47 C-HCC patients without HCV eradication as controls. Primary end point was time to curative treatment failure. We defined time to curative treatment failure as the interval from curative treatment initiation to premature discontinuation of this type of therapy. Their clinical data, time to curative treatment failure and overall survival were compared. We also assessed the prognostic values of time to curative treatment failure and overall survival using multivariate Cox proportional hazard models. The median age was 74.8years, 60 patients (63.8%) were male, and 81 patients (86.2%) were Child-Pugh class A. The median tumour number was 1, tumour diameter was 20mm, and frequency of recurrence was 3 times. There were no significant differences about patients' backgrounds between the 2 groups. The cumulative time to curative treatment failure rates of patients who received DAA were 93.6% and 73.2% at 1 and 3years, respectively; those of controls were 72.5%, and 37.1% (p<.01). Multivariate analysis indicated that eradication with DAAs (HR 0.23, 95% CI; 0.12-0.43, p<.01) and DCP>50mAU/ml (HR 2.62, 95% CI; 1.45-4.74, p<.01) as independent factors contributed to time to curative treatment failure. The cumulative overall survival rates of patients who received DAAs were 93.6% and 72.6% at 1 and 3years, respectively; those of controls were 72.8% and 37.4% (p<.01). Multivariate analysis indicated that eradication with DAAs (HR 0.32, 95% CI; 0.17-0.60, p<.01) and frequency of recurrence times (HR 1.20 per 1 time, 95% CI; 1.01-1.42, p=.038) as independent factors related to overall survival. Eradication of HCV using DAAs prolonged not only time to curative treatment failure but also overall survival even in C-HCC patients with multiple courses of recurrence.

P-117 LOW PREVALENCE OF HEPATITIS B AND C AMONG PEOPLE LIVING IN POVERTY IN NORTHEAST BRAZIL

Hepatitis B and C infection are responsible for more than 300 million of chronic liver disease patients all over the world. One goal of WHO 2030 agenda is the eradication of hepatitis B and C. However poverty is a great obstacle to achieve this goal. In Brazil, more than 13 million of people live in poverty (PLP) and could be vulnerable to HBV and HCV. This study aims to determine HBV and HCV prevalence and analyze the response to HBV vaccination by measuring anti -HBs antibodies in serum samples from PLP. This was a cross­ sectional study carried out in rural settlement in the municipality of Sao Joao do Piaui, Northeast Brazil in March and July 2019. Participants were recruited in their homes and after signing the informed consent, they gave blood samples. A commercial ELISA was use d for measurements of antibodies against i) hepatitis B surface antigen (anti-HBs) and ii) hepatitis B core antigen (HBc) and of the hepatitis surf ace antigen (HBsAg). Nearly half of the population was female (51.0%). The mean age was 36.2±20.4 years, and about 43.2% received a monthly income of approximately $35.00 USD. Most are self­declared black or mixed race (81.9%), were married (50.1%), 15.5% was illiterate and 25.8% had a maximum of six years of formal schooling. Overall zero positivity for HBsAg, anti-HBc and anti -HBs determined by ELISA was 0.2%, 5.1 % and 43.9%, respectively. Anti-HBs reactivity was not associated with monthly income and schooling. Low rates of vaccination against hepatitis B were found among PLP in Northeast Brazil, highlighting the need for preventive actions towards this population segment, vulnerable and a potential disseminator of this infection. Strategies to increase HBV vaccination will be essential to eradicate hepatitis Band achieve the goals of WHO 2030 agenda. Report the levels of biochemical markers in CLD patients with or without COVID-19 to give more information that could help clinical monitoring. Study was approved by Brazilian Ethics Committee. Blood samples were collected after signed informed consent. Most of individuals were male 56% (37/66) and mean age of population was 49±17 years. Six out 66 CLD patients were SARS CoV-2 RNA positive at baseline. At the end of follow-up, all of these 6 patients achieved SARS-CoV-2 clearance. At least once during follow-up, the CLD group versus CLD/COVID-19 group, 48% (29/60) vs. 17% (1/6) (P = 0.2) had abnormal alanine aminotransferase; 47% (28/60) vs. 17% (1/6) had abnormal aspartate aminotransferase (P = 0.21); 60% (36/60) vs. 67% (4/6) had abnormal γ-glutamyl transferase (P = 1.00), 32% CLD patients (19/60) had abnormal total bilirubin levels vs. none of the CLD/COVID-19 group (P = 0.17). Previous liver disease did not seem to increase the biochemical levels, except GGT, during COVID-19 infection. However, liver function monitoring is still essential for both COVID-19 patients with and without liver disease.

Non-Invasive Indirect Markers of Liver Fibrosis after Interferon-Free Treatment for Hepatitis C.

The effectiveness of interferon-free therapy during the course of HCV infection has already been confirmed. Liver fibrosis can be assessed in several ways, from biopsies to imaging tests. The present study evaluates the usefulness of non-invasive indirect biomarkers of liver fibrosis (APRI, GAPRI, FORNS, FIB-4, the AP index and HUI score) as markers of the effective treatment of HCV with the 3D regimen. Blood samples were collected from 70 patients suffering from chronic hepatitis C. Patients received the 3D AbbVie regimen for hepatitis C. All patients had HCV genotype 1b. The APRI, GAPRI, FIB-4, FORNS, HUI and AP index (age–platelet score) values were calculated with their respective algorithms. The stage of fibrosis was evaluated on the basis of a liver biopsy and confirmed by FibroScan-based transient elastography. An undetectable level of HCV RNA after 12 weeks of treatment with the 3D regimen indicates 100% eradication of hepatitis C virus. After the treatment, non-invasive indirect markers of liver fibrosis achieved levels below the limit for significant fibrosis, Thus, non-invasive indirect biomarkers of hepatic fibrosis failed to detect the presence of significant fibrosis, which was proved in histopathological examination. However, the eradication of hepatitis C virus by means of the 3D regimen treatment does not mean that patients were completely cured.

Long Term Effects of Leptin on Hepatic Fibrosis in Generalized Lipodystrophy

Lipodystrophy syndromes are caused by deficiency of adipose tissue leading to severe insulin resistance, hypertriglyceridemia, and non-alcoholic fatty liver disease (NAFLD), which may progress to cirrhosis. Advanced fibrosis/cirrhosis was previously thought to be irreversible; however, eradication of hepatitis C or long-term viral suppression of hepatitis B can reverse cirrhosis. Metreleptin treatment in patients with lipodystrophy improves liver transaminases and NAFLD activity score (NAS) after a mean of 2 years, but the latter improvements were due to lower inflammation and steatosis, with no change in fibrosis. The long-term effects of metreleptin in subjects with advanced fibrosis are unknown. We analyzed 24 subjects with advanced fibrosis (NAS stage 3 or 4) prior to metreleptin. Seven had liver biopsies both before and after ≥ 3 years of metreleptin with mean treatment duration 7.8±2.9 years. Five of six subjects with stage 3 fibrosis at baseline had improved fibrosis scores after metreleptin, and 0 of 1 with stage 4 fibrosis improved. 17 patients (8 with stage 3, 9 stage 4) did not have follow up biopsies after ≥3 years. Of these 17, 4 (all stage 4) died from end stage liver disease, and 1 (stage 3) from other causes. There was no clinical indication for repeat biopsy in 6 patients (2 stage 3, 4 stage 4). 6 were lost to follow up. Of the 24 patients with advanced fibrosis, 13 had congenital generalized lipodystrophy (CGL), 7 had acquired generalized lipodystrophy (AGL), 3 had familial partial lipodystrophy (FPL) and 1 had acquired partial lipodystrophy (APL). Of the 5 subjects with improvement in their fibrosis score, 2 had AGL, 2 had CGL, and one had a novel FPL mutation (1). Of the two patients that did not improve, one had FPL and one had CGL. In conclusion, subjects with stage 3 fibrosis due to lipodystrophy may have regression of fibrosis after long-term metreleptin treatment. This improvement may be secondary to near-elimination of the inciting factors (excess nutrient intake leading to ectopic lipid storage in the liver), analogous to clearance of Hepatitis C infection. However, additional data is needed to determine if metreleptin can reverse fibrosis in subjects with stage 4 fibrosis.