HCV Eradication Research Articles

Non-liver malignancies as main cause of mortality after HCV eradication among people living with HIV.

In people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs. Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade. Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049]. In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended.

Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study.

Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5years after successful HCV treatment) in persons with HIV/HCV coinfection. We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

Impact of HCV eradication on recurrence pattern and long-term outcomes in patients with HCV-related hepatocellular carcinoma undergoing radiofrequency ablation.

The benefits of HCV eradication on distinct recurrence patterns and long-term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long-term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR). We retrospectively enrolled 274 patients receiving RFA for HCV-related HCC, including 73 and 88 patients treated with interferon-based (IFN) and direct-acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation. SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB-4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB-4 score after SVR, rather than the baseline FIB-4, predicted distant recurrence. HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV-related HCC.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry

Background/AimsHepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. MethodsData from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). ResultsSerum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00–1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48–3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05–1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000–1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006–1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52–4.45, P < 0.001). ConclusionsThe HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. Aim of the Work The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Patients and Methods Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level. Results Among 40 patients; 26 (65%) are males and 14 (35%) are females. Their age is ranged between 35 and 60 years old with a mean age of 52.35 ± 6.08 and a median of 53.0 (50.0 – 57.0). The HCV-RNA titer is ranged from 3.60 to 7.20 log IU/mL with a mean titer of 5.99 ± 0.87 before treatment. The median is 6.20 (5.30 – 6.65). There was a significant improvement concerning the fibrosis stage after DAA treatment. Liver fibrosis indices were significantly associated with regression of liver fibrosis stage based on FibroScan data after DAA therapy. Liver size, spleen size and portal vein diameter were improved significantly after successful HCV eradication by DAAs. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant (p = 0.500). Baseline Ang-2 was statistically significant after successful HCV eradication by DAAs (p &amp;lt; 0.001). Overall, there was a positive significant correlation between Ang-2 and all the fibrosis stages (p = 0.001) and there was a statistically significant higher mean of Ang-2 in higher stages of liver fibrosis before treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa before treatment. Ang-2 in higher stages of liver fibrosis after treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa after treatment. The correlation between Ang-2 and fibrosis group (F0, F1, F2 &amp; F3) were significant and the correlation between Ang-2 and the liver fibrosis stage (F4) were also significant before treatment. The correlations between Ang-2 levels and fibrosis group (F0, F1, F2 &amp; F3) were significant as well as the advanced liver fibrosis (F4) after DAA therapy. Conclusion Angiopoietin-2 can be a useful predictor of fbrosis regression in chronic HCV patients receiving direct acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced ibrosis stages may predict non-regression of liver fibrosis.

Perspective of the risk and molecular mechanisms of hepatocellular carcinoma after HCV eradication in the post-DAA era: Correspondence to editorial on "Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication".

Perspective of the risk and molecular mechanisms of hepatocellular carcinoma after HCV eradication in the post-DAA era: Correspondence to editorial on "Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication".

Treatment Revolution: The New Era Against Hepatitis C

Abstract In recent decades, chronic viral infection C (HCV) has posed a major public health challenge globally, considering the morbidity and mortality associated with this condition, as well as the difficulties related to diagnosis and treatment. Recently, significant advances in medical and pharmaceutical research have led to the development of new direct-acting antiviral therapies (DAAs), marking the beginning of a new era in HCV treatment. These treatments promise cure rates of over 90%, an improved safety profile, and a reduced duration of therapy compared to previous interferon-based regimens. This article aims to examine the evolution of HCV treatment, with a special focus on recent innovations in antiviral therapy. We will analyze the mechanisms of action of DAAs, their efficacy and safety, and their impact on populations with limited access to treatment. Additionally, we discuss the remaining challenges in the path to HCV eradication, including late diagnosis, barriers to treatment access, and the need for long-term monitoring of cured patients. By consolidating data from recent clinical studies and reviewing the specialized literature, this article provides a comprehensive perspective on the current landscape of HCV treatment, highlighting significant progress made and underlining the future directions needed to address remaining challenges. Finally, we reaffirm the importance of an integrated approach, encompassing prevention, early diagnosis, and universal access to innovative treatments, as a cornerstone in the fight against HCV.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Predicting de-novo portal vein thrombosis after HCV eradication: A long-term competing risk analysis in the ongoing PITER cohort.

Sustained virological response (SVR) by direct-acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non-tumoral PVT in patients with cirrhosis after HCV eradication. Patients with HCV-related cirrhosis, consecutively enrolled in the multi-center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan-Meier and competing risk regression analyses were performed. During a median time of 38.3months (IQR: 25.1-48.7months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. Aplatelet count ≤120,000/μL, albumin levels ≤3.5mg/dL, bilirubin >1.1mg/dL, a previous liver decompensation, ALBI, Baveno, FIB-4, and RESIST scores were significantly different (p<0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33-24.99) and pre-treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36-13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p<0.001) versus pre-treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p>0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16-27.53 and subHR: 5.50; CI 95% 1.67-18.13, respectively). In patients with HCV-related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

Global Elimination of HCV-Why Is Poland Still So Far from the Goal?

Eradication of HCV in the global population remains one of the greatest challenges faced by the WHO. An insufficient level of knowledge and the lack of a national screening test strategy are obstacles to HCV eradication. This work aimed to summarize surveys assessing risk factors and awareness of the respondents regarding the prevention and course of HCV infection. The summary also includes the most important European and global attempts at eliminating HCV. A cross-sectional, population-based study was conducted in the Mazowieckie district in Poland using anonymous surveys and conducted on people who willingly reported for a test. In the study cohort of n = 7397 adults, there were 5412 women (73.16%). The analysis of the quota sample (n = 1303) reflected the actual proportions in the population of the Mazowieckie Voivodeship. Insufficient knowledge about HCV decreases the probability of higher detection of infections, fast diagnostics, and treatment. According to the WHO model, assuming a 90% detection rate and treatment of 80% of infected by 2030, and taking into account 120-150 thousand infected persons in Poland, the number of detections of HCV should be increased 4-5 times and all diagnosed persons should be offered antiviral treatment.

The impact of HCV eradication using interferon-free direct acting antivirals on bone-mineral, anemia parameters and peripheral insulin resistance in hepatitis c-infected Egyptian hemodialysis cohort

BackgroundHepatitis C virus (HCV) infection is linked to a higher mortality rate in hemodialysis (HD) patients. We aimed to see if HCV eradication using interferon-free direct acting antivirals (DAAs) can affect bone-mineral and anemia biochemical parameters such as serum calcium (Ca++), phosphorus (PO4+), parathormone (PTH), fibroblast growth factor 23 (FGF23), hemoglobin (HB), and ferritin in HD patients and also peripheral insulin resistance by monitoring serum fasting insulin and HOMA insulin resistance (HOMA-IR).MethodsThree hundred and thirty-four adults on regular HD with positive HCV genotype 4 (191 male and 143 female) were included; 157 of them had seroconversion during HD. All were hepatitis B virus (HBV) negative and received treatment with DAAs. All cases were examined for body mass index (BMI), HB, ferritin level, transferrin saturation (TSAT), Ca++, PO4+, PTH, FGF23, serum albumin, alanine transaminase (ALT), fasting insulin level, and HOMA-IR at the beginning and then were measured after 6 and 12 months from a sustained virological response (SVR).ResultsAfter 6 and 12 months from SVR, there was a significant increase in serum Ca despite no change in oral calcium dose requirement over that period (p = 0001), a significant increase in HB, serum iron (p = 0001), and a significant reduction in serum ferritin, PO4, PTH, and FGF23 (p = 0001). Both fasting insulin level and HOMA-IR were statistically significantly dropped.ConclusionHCV eradication with interferon-free DAAs showed a statistically significant impact on hemodialysis patients regarding hemoglobin, ferritin level, bone-mineral parameters, and improvement in peripheral insulin resistance.

Therapy with direct antiviral drugs in patients with HCVassociated cryoglobulinemic vasculitis – is it always possible to achieve complete clinical and immunological responses after the virus eradication?

Background. The use of direct acting antiviral drugs (DAАs) leads to the achievement of a stable virological response (SVR) in 95–100 % of patients with HCV-associated cryoglobulinemic vasculitis (HCV-CV). However, in some patients, despite the eradication of the virus, clinical and immunological markers of vasculitis still remain.The aim: to evaluate clinical and immunological responses in patients with HCV-CV in comparison with patients with "asymptomatic" HCV- associated cryoglobulinemia (HCV- СG) after achieving SVR with the help of DAАs with long-term dynamic observation (12 months).Patients and Methods: The study included 45 patients: 23 with HCV-CV and 22 with "asymptomatic" HCV-CG, who underwent antiviral therapy with DAAs. Clinical-immunological, virological data were evaluated: before treatment, 12 weeks (3 months) and 48 weeks (12 months) after the end of treatment.Results: After a course of DAAs, SVR was diagnosed in all 45 (100 % of patients). In patients with HCV-CV, an immunological response (complete and partial) was observed by week 12 (SVR12) – in 56.5 % and by week 48 (SVR48) – in 73.9 % patients. In 6 patients (26.1 %), the immunological response was not achieved by SVR48. The rate of complete and partial clinical response 12 weeks after the end of treatment at the SVR12 period in patients with HCV-CV was 65.2 %, to the time of SVR48 amounted to 78.3 % patients. In 5 (21.7 %) individual manifestations of CV persisted and/or relapsed. In patients with HCV-CG, the frequency of complete and partial immunological responses after DAAs therapy was 77.3 % – by SVR12 and 86.3 % – by SVR48, respectively. No response was observed in 3 patients and it was characterized by trace-level of cryoglobulinemia.Conclusion: In most patients with HCV-CV eradication of HCV with help of DAAs leads to the achievement of clinical and immunological remission of the disease. However, in 20 % of patients manifestations of HCV-CV persist / recur immediately after the end of treatment or later relapses are observed. Based on these observations, patients with HCV-CV, especially those with severe underlying skin and kidney disease, are required long-term monitoring after SVR is achieved.

Screening of Cirrhotic Compensated Hepatitis C Virus Infected Patients Who Received Oral Direct Acting Antiviral Drugs for Hepatocellular Carcinoma and Other Malignancies

Abstract Background HCV is now recognized as a major factor in the development of severe liver damage as chronic infection is associated with the development of hepatic steatosis, cirrhosis and hepatocellular carcinoma. Aim of the Work screening of our patients for the incidence of hepatocellular carcinoma and other malignancies during or after end of treatment with orally direct acting antiviral drugs to prove or disprove this allegation. Patients and Methods This retrospective observational study was performed at Maadi Military Hospital during the period from July 2015 to July 2016 including 290 naive compensated cirrhotic hepatitis C virus infected patients with no prior history of hepatocellular carcinoma or any other malignancy and divided into 5 groups: Group (A) patients treated with combined sofosbuvir and ribavirin for 24 weeks. Group (B) patients treated with combined sofosbuvir and daclatasvir and low dose ribavirin for 12 weeks. Group(C) patients treated with combined sofosbuvir and ledipasvir with weight based ribavirin for 12 weeks. Group (D) patients with chronic renal failure on regular hemodialysis treated with combined ompitasvir+paritaprevir+ritonavir and low dose ribavirin for 12 weeks. Group (E) patients with the same criteria were taken from the waiting list of treatment and studied as the control group and were subjected to the same investigations and follow up. Results Highly significant increase in HCC prevalence in A group (23.3%) during follow up period. Significant increase in HCC prevalence in B group (8%) during follow up period. Non-significant difference in HCC prevalence in C group; during follow up period. In group D; non-significant difference in HCC prevalence during treatment and follow up periods. There was no detected occurrence of HCC or any other malignancies during the course of the study in group E. Conclusion Increased HCV detection combined with the availability of simple, well-tolerated treatment regimens can potentially reduce the need for liver transplantation and reduce HCV-related mortality. No evidence of an increased risk of de novo HCC by patients treated with interferon free SOF-based regimens. However, cirrhosis was strongly associated with the short-term development of HCC after HCV eradication. Treatment of HCV in patients with CKD is highly effective, with SVR12 rates similar to those seen in patients without CKD. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial. Aim of the Work to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs. Patients and Methods This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals. All patients were subjected to the following: Full history taking with stress concerning the hepatology system, clinical evaluation, laboratory investigations, Routine investigations: Abdominal and Pelvic ultrasonography and Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients. Results Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy. There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12. The liver size, the spleen size and portal vein diameter were also significant after DAA therapy. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant. There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages. Overall, serum Ang-2 levels significantly decrease after DAA therapy. In F0, F1, F2 &amp; F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost. Baseline Ang-2 and WBCs, AST, ALT, total bilirubin, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated. There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment. Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy. Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline. Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy. Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy. Conclusion Liver fibrosis stage after successful HCV eradication by DAAs. But in stage F4 (cirrhosis), mean Ang-2 remained almost unchanged after DAA therapy. Significant decrease of Serum Ang-2 could suggest its use as a predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs after DAA therapy.

Revaccination for Hepatitis B in Previous Nonresponders Following Hepatitis C Eradication.

Patients with chronic hepatitis C virus (HCV) do not respond to hepatitis B virus (HBV) vaccination as efficiently as the general population. We assessed if revaccination after HCV treatment resulted in improved response. Previous HBV vaccine nonresponders were prospectively recruited for revaccination after HCV eradication. Hepatitis B surface antibody (HBsAb) testing was performed 1 month after series completion. Follow-up HBsAb testing was performed in 31 of 34 enrolled patients with 21 (67.7%) reactive results. There were no significant differences in HBsAb reactivity based on age, sex, race, or advanced fibrosis presence. HBV vaccine nonresponders should be considered for revaccination following HCV cure.

Effect of viral eradication with direct-acting antiviral agents on iron parameters in patients with chronic hepatitis c and hyperferritinemia.

Patients with chronic hepatitis C are at increased risk for hyperferritinemia (HF). Abnormalities of serum iron parameters are frequently observed in patients with chronic hepatitis C (CHC). About a third of patients have increased iron parameters. Recently, studies on the effect of direct-acting antiviral agents (DAAs) in HCV eradication in patients with increased serum iron has been published, demonstrating the restoration of normal iron status. The aim of this study was to evaluate the effect of viral eradication with DDAs in patients with CHC and HF. Retrospective study conducted from January 2018 to December 2020 including patients treated with DAAs for HCV. Pre-treatment (PreT) and post-treatment (PostT) serum ferritin values were evaluated in all patients. Inclusion criteria: Pret HF (>400 μg/L); CHC patients treated with DAA achieving sustained viral response (SVR). Exclusion criteria: No PreT or PostT HF available; no SVR; lost patients. From 621 patients treated with DAAs for CHC, 77 presented HF (12.40%), and 74 were included in the study. Fifty nine were men (79.73%) with a mean age 58.33, SD 8.68; PreT mean ferritin: 893.20 (SD 1037.09); PostT: 264.17 (SD 161.33); PreT mean transferrin saturation: 40.96 (SD 15.71); PostT: 29.82 (SD 11.17); PreT mean serum iron 152.32 (SD 62.07), PostT: 109.32 (SD 39.49). When we compared PreT and PostT iron parameters, significant statistical differences were present considering ferritin (p = 0.0000), transferrin saturation (p = 0.0000), and iron (p = 0.0002) determinations. SVR after DAAs for CHC induces a statistically significant reduction on iron parameters.

Hepatitis C antibody prevalence and active hepatitis C infection in HIV-negative gay, bisexual, and other men who have sex with men in Barcelona and Madrid, Spain (March 2018-March 2021)

ObjectivesHepatitis C virus (HCV) has been recognized as a sexually transmitted infection (STI) in HIV-positive men who have sex with men (MSM), with an increased notification in HIV-negative MSM. The aim of this study was to determine the prevalence of HCV antibody and active HCV infection in HIV-negative gay, bisexual, and other MSM (GBMSM), and their characteristics, in Barcelona and Madrid, from March 2018 to March 2021. MethodsCross-sectional study conducted on 3548 HIV-undiagnosed GBMSM, across four HIV/STI testing centers. Respondents submitted an online, self-administered questionnaire after consultation, which collected information on sociodemographics, sexual health history, HCV knowledge, and substance consumption. Prevalence of HCV antibodies was determined by a reactive result in a rapid anti-HCV test or enzyme-linked immunosorbent assay (ELISA), while active HCV infection was determined by participants who were also positive on an HCV-RNA test. Crude and adjusted Poisson analyses with robust variance are presented for both prevalence and active infection. ResultsIn total, 97.6% of participants (n = 3463) were HIV-negative. Of those, 18 were found to have HCV antibodies (0.52%), of which nine (0.26%) were also HCV-RNA positive. Those with HCV antibodies were associated to have lived with an HCV (+) person (adjusted prevalence ratio [APR]: 7.84, [95% confidence interval: 2.50-24.53]), using injectable drugs for sex (APR: 6.92, [1.20-39.79]) and testing positive for an STI in the previous year (APR: 4.06, [1.09-15.12]). Presenting an active infection was strongly associated with a previous HCV diagnosis (APR: 100.82 [22.16-458.76]), sexualized injectable drug use (APR: 17.53 [2.70-113.76]), and sharing douching material (APR: 7.45, [2.12-25.95]). ConclusionSexual practices with a higher risk of bleeding and sexualized drug use, particularly sexualized injectable drug use, were associated with higher rates of HCV diagnosis in GBMSM. Identifying these practices during consultation, contact tracing new cases and regularly testing those with a previous history of HCV, will facilitate HCV eradication.

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort.

Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.

Hepatic Steatosis in Patients with Chronic Viral Hepatitis C Treated with Direct Acting Antivirals

Abstract Hepatic steatosis is a frequent pathological finding in patients with chronic viral C infection (HCV) and can be independently associated with increased alcohol consumption, type 2 diabetes, obesity and hyperlipidemia. All these factors can lead to the development of hepatic steatosis in patients with HCV. There are several noninvasive techniques and scores used for diagnosing and quantifying liver steatosis. Successful eradication of HCV with interferon-free treatment regimens has been suggested to improve the level of hepatic steatosis. The precise mechanisms responsible for these beneficial effects are currently under investigation, but it is thought that the decrease in hepatic inflammation and viral replication contribute to the resolution of hepatic steatosis. Moreover, the overall enhancement in liver health and metabolic factors may also have a significant impact.

LBP-29 - Predictors of long-term mortality after HCV eradication among PLWH

LBP-29 - Predictors of long-term mortality after HCV eradication among PLWH