Direct Antiviral Agents Therapy Research Articles

Occult hepatitis C infection identified in injection drug users with direct antiviral agents therapy and spontaneous resolution of hepatitis C virus infection

BackgroundOccult hepatitis C infection (OCI) is characterized by the detection of hepatitis C virus (HCV) RNA in hepatocytes and in peripheral blood mononuclear cells (PBMCs) without detection in serum. We aimed to evaluate OCI in drug and no drug users who achieved sustained virological response (SVR) after therapy with direct-acting antivirals (DAAs) and with HCV spontaneous resolution. MethodsTwenty-four patients in the AVP group (who achieved a SVR after DAAs therapy), 13 in the NAVP group (with HCV spontaneous resolution) and 7 HCV-RNA positive patients (CPP, control positive group) were included in the study. HCV/OCI-RNA was screened in serum and PBMCs samples of the patients by ddPCR for OCI patients’ identification. Plasma and red blood cells (RBCs) samples of the patients were also evaluated for HCV/OCI-RNA detection by ddPCR. ResultsOCI was presented in injection drug users (IDUs) in the AVP (20.8%) and NAVP (23.1%) groups by ddPCR with a higher statistically significant percentage detected in RBCs samples of the patients in the AVP group comparatively to NAVP (p<0.01) and CPP (p < 0.05) groups. ConclusionOCI was identified in IDUs patients of the AVP and NAVP groups by ddPCR. These results suggest that OCI patients in the AVP group might not be entirely cured, and that OCI patients in the NAVP group were not identified at clinical evaluation time when just serum samples were analysed. A higher percentage of HCV/OCI-RNA was detected in RBCs samples. Overall results recommends that HCV/OCI identification in patients with DAAs therapy and spontaneous resolution of HCV infection should be studied more accurately in future and in larger patient groups if possible. Additionally, suggest also PBMCs and RBCs samples as predictors for HCV/OCI diagnosis and management.

Hypergammaglobulinemia before Starting DAA Therapy Is A Strong Predictor of Disease Progression in Cirrhotic Patients Even after HCV Clearance.

The predictive factors of long-term clinical benefits in patients with hepatitis C virus (HCV)—related liver cirrhosis after Direct Antiviral Agents (DAA) treatment are still undefined. The aim of this study was to identify any predictors of liver failure, hepatocellular carcinoma (HCC) and/or death in patients with compensated liver cirrhosis who achieved the sustained virological response (SVR). To this purpose, 324 consecutive cirrhotic patients who started DAA treatment from 1 April 2015 to 31 December 2016 were retrospectively analyzed. All patients were followed up for a median time of 63 months (range 19−77) through clinical/biochemical/instrumental examinations performed at baseline and after stopping the DAA treatment. At the end of the evaluation, 230 (71%) individuals showed stable clinical liver disease over time, 43 (13.3%) developed HCC, and 24 (7.4%) developed hepatic decompensation without HCC. Overall, 49 (15,1%) patients died. Multivariate regression analysis showed that hepatic decompensation was significantly associated with at baseline older age, higher liver stiffness, higher spleen longitudinal size values and hypergammaglobulinemia (p = 0.003, p = 0.005, p = 0.001, p = 0.029, respectively). HCC development was significantly associated with hypergammaglobulinemia (p < 0.001). Death was associated with older age and hypergammaglobulinemia (p < 0.001 and p = 0.007, respectively). Finally, survival analysis confirmed that patients with gamma globulin levels ≥ 1.8 gr/dl had a significantly higher risk of death compared to those with gamma globulin levels < 1.8 gr/dl (p < 0.001). In conclusion, hypergammaglobulinemia before starting DAA therapy represents a strong predictor of hepatic decompensation, HCC and death in cirrhotic patients even after HCV clearance.

Hepatitis C virus-associated B-cell lymphomas: The importance of the new direct antiviral agent therapy

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus, responsible for both chronic hepatitis and extra-hepatic manifestations. Multiple epidemiologic, clinical, biological, and molecular studies have suggested that HCV plays a causal role also in the development of several lymphoproliferative disorders, either benign, such as mixed cryoglobulinemia, or malignant, such as B-cell non-Hodgkin lymphomas (NHL). Chronic viral antigenic stimulation of B-lymphocytes plays a fundamental basic role from the onset of lymphoma to its final steps. In the past, several studies demonstrated that the association of pegylated interferon plus ribavirin was able to eradicate HCV, with subsequent regression of indolent B-cell low-grade NHL. Other studies have demonstrated that direct antiviral agents (DAAs) therapy have some efficacy in HCV-associated NHL, particularly in patients with low-grade NHL or marginal zone-lymphoma, but these results need to be confirmed in larger studies with longer follow-up. The response rate of antiviral therapy seems favorable also in high grade NHL when DAAs therapy is administered in combination with chemotherapy and therefore antiviral therapy should be considered as a first-line approach in HCV-related NHL.

Direct antiviral therapy for hepatitis C cirrhotic patients in liver transplantation settings: a systematic review.

Hepatitis C (HCV)-induced decompensated cirrhosis warrants liver transplantation (LT) as the only ultimate solution. These patients experience liver deterioration, while on the transplant waitlist. However, debate remains over the optimal timing for treating HCV relative to before or after LT. We performed a literature search between 1/2011 and 1/2022 on PubMed and OVID Medline. Data were extracted from direct antiviral agent (DAA) studies in English. The outcomes of interest included sustained virological response (SVR) rates from various cohorts as well as long- and short-term outcomes in the LT settings. After screening, 54 studies were eligible and included into the review. In aligning with the EASL and AASLD guidelines and suggestions, many studies supported DAA therapy before LT in patients with Model for End-stage Liver Disease (MELD) scores < 18 and DAA therapy post-LT in MELD scores > 20 through SVR rates, long-term survival factors, liver deterioration, and incidences of severe adverse events. However, uncertainty still lies in the guideline recommendations and unsettled issues remain for various patient cohorts that may benefit from opposing the guideline cutoffs. Based on the recent studies on predictors of treatment outcomes in decompensated patients and the impact of DAA on the waiting list for LT, we proposed an algorithm to manage patients with MELD scores between 18 and 20. DAA therapy for decompensated patients must be personalized with consideration of different factors, particularly among those with MELD scores between the two cutoff-values proposed by the current associational guidelines.

THU349 - Occult hepatitis C infection detection in people who use drugs with or without direct antiviral agents therapy

THU349 - Occult hepatitis C infection detection in people who use drugs with or without direct antiviral agents therapy

Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

HEPATOCELLULAR CARCINOMA AFTER DIRECT ANTIVIRAL AGENTS FOR HEPATITIS C IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

If direct antiviral agents (DAA) are related to the development of HCC is controversial; therefore, exploring risk factors are crucial. We aimed to determine factors related to the development of hepatocellular carcinoma (HCC) in patients with hepatitis c (HCV) and decompensated cirrhosis (DC) treated with DAA. A multicenter real-world cohort study including patients with HCV + DC treated with sofosbuvir (SOF) based on regimens free of inhibitors of protease (IPs). 222 patients, 118 (53.2%) were women, mean age 57.2 ±11.5-year-old, 209 (94.1%) achieved sustained virological response (SVR). According to Child-Pugh 44(19.8%) were A with history of any clinical decompensation event, 147(66.2%) B, and 31 (14%) C. After DAA, 134 (60.4%) improve in MELD, 45 (20.3%) had no change, and 43 (19.4%) worse, this worse in MELD was related to non-SVR [SVR 37/209 (17.7%) vs. non-SVR 6/13 (46.2%); OR=2.6, 95%CI:1.4-5.0, p =0.02]. Nineteen (8.6%) developed HCC during the follow-up after therapy with DAA; however, when we compared basal laboratory values between those who developed HCC and those who did not only alfa-fetoprotein (AFP) levels were different (without HCC 14.3 [mean 95%CI: 10.6-18.1] ng/mL vs. HCC 55.7 [mean 95%CI: 28.4-83.0] ng/mL; p <0.006). Univariate and multivariate analyses are shown in Table 1. Our study confirms that rather than DAA therapy, the most critical factors related to the development of HCC in DC patients with HCV treated with DAA, are non-achieve SVR and, most important basal AFP levels > 20ng/mL, it is essential to note that patients in this cohort had no any suspicious lesion in ultrasonography (USG) previous to start DAA therapy in their semestral screening as most of the guidelines recommend. AASLD, for example, recommends semestral HCC screening with USG with or without AFP, giving more weight to the imagen study. However, based on our results, we recommend always determining AFP levels as a compliment to USG. In HCV patients with DC treated with DAA and with a negative basal screening USG for suspicious malignant lesions, basal AFP > 20ng/mL are the most critical factor related to the development of HCC and should be determined complementary to the USG study. The authors declare that there is no conflict of interest.

Out-of-Hospital Treatment of Hepatitis C Increases Retention in Care among People Who Inject Drugs and Homeless Persons: An Observational Study.

Background. People who inject drugs (PWID) and homeless people represent now a large reservoir of Hepatitis C virus (HCV) infection. However, Hepatis C elimination programs can barely reach these subgroups of patients. We aimed to evaluate and compare the retention in care among these difficult-to-treat patients when managed for HCV in hospital or in an out-of-hospital setting. Methods. In our retrospective study, we categorized the included patients (PWID and homeless persons) into two groups according to whether anti-HCV treatment was offered and provided in a hospital or an out-of-hospital setting. We run logistic regressions to evaluate factors associated with retention in care (defined as the completion of direct antiviral agents (DAAs) therapy). Results. We included 56 patients in our study: 27 were in the out-of-hospital group. Overall, 33 patients completed DAAs therapy. A higher rate of retention in care was observed in the out-of-hospital group rather than in-hospital group (p = 0.001). At the univariate analysis, retention in care was associated with the out-of-hospital management (p = 0.002) and with a shorter time between the first visit and the scheduled start of DAAs (p = 0.003). Conclusions. The choice of treatment models that can better adapt to difficult-to-treat populations, such as an out-of-hospital approach, will be important for achieving the eradication of HCV infection.

Study of hepatitis B virus infection, reactivation among patients with chronic hepatitis C infection treated by direct antiviral agents (DAAs)

BackgroundHepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct-acting antivirals (DAA). We aimed to investigate the risk of HBV infection and reactivation during DAA therapy by performing a prospective observational study carried on 200 patients positive for chronic HCV who were candidates for treatment by DAA therapy according to the Egyptian guidelines from February 2019 to December 2019; the patients identified to carry HBsAg at baseline or with positive HBc Abs were further assessed for other HBV markers: hepatitis B e antigen at baseline, and serum HBV DNA quantitative measurement at baseline, week 4 of treatment, end of treatment. On the other hand, recent infection by HBV among those patients was observed.ResultsOf all participants, 49% were males and 51% were females, aged above 18 years. There is a highly statistically significant difference (p-value < 0.05) between HCV RNA PCR (at the beginning, at the end of 4 weeks, and at the end of 12 weeks) in studied patients. There was a highly statistically significant difference found between the liver function tests at the beginning, at the end of 4 weeks, and at the end of 12 weeks of treatment where it shows improvement except for serum albumin. At beginning of the study, there were 34 patients who are co-infected with HCV and HBV with quantitative PCR test for HBV DNA ≥ 20 IU/ml. After 1 month of DAA therapy, reactivation was detected in 6 cases (4 occult cases show reverse seroconversion (became HBs Ag positive), and 2 co-infected cases show increased HBV DNA > 1000 IU/L above the baseline level). In addition, 3 new cases acquired recent infection with the positivity of HBc IgM and detectable levels of HBV DNA. After 3 months of study, reactivation was detected in one patient with co-infection (where increased HBV DNA > 1000 IU/L above the baseline level), and 5 new cases acquired recent infection late in the study.ConclusionScreening for HBV infection prior to DAA therapy is required to detect recent infection of reactivation of previous infection during or after DAA therapy.

Characterizing a cohort of Egyptian patients with acute-on-chronic liver failure

Several studies performed in Western countries and Asia have shown that acute-on-chronic liver failure (ACLF) is an acute decompensation of cirrhosis characterized by organ system failures and high short-term mortality. However, the characteristics of Egyptian patients with ACLF have not yet been described. The aim of this study was to assess Egyptian patients with cirrhosis hospitalized for an acute decompensation using criteria and scores developed by the EASL-CLIF Consortium. One hundred and twenty patients with acutely decompensated cirrhosis nonelectively admitted to two tertiary hospitals were prospectively included. Ninety-three percent of patients had hepatitis C virus-related liver disease. Of the 120 patients, 40 had ACLF; of these 45% had ACLF-1, 33% ACLF-2, and the remaining 22% had ACLF-3. None of the patients with ACLF had received direct-antiviral agents (DAAs) while 30% of patients without ACLF were treated with these agents. The prevalence of prior episodes of decompensation was significantly higher in patients with ACLF (60% vs. 28%). The prevalence of precipitating events such as bacterial infection alone or combined with gastrointestinal hemorrhage was higher in patients with ACLF than in those without. Systemic inflammation, assessed with white blood-cell count and plasma C reactive levels, was more intense in ACLF. Among Egyptian patients with acutely decompensated cirrhosis nonelectively admitted to the hospital, those with ACLF were distinct from those without ACLF, not only by the presence of organ failures, but also the absence DAA therapy, more frequent prior episodes of decompensation, more frequent bacterial infections as a precipitant, and more intense systemic inflammation.

Genotype distribution, clinical characteristics, and racial differences observed in chronic hepatitis C patients in Pingtung, Taiwan.

The World Health Organization (WHO) set out to eliminate hepatitis C virus (HCV) infection by 2030, a goal Taiwan might achieve before 2025. Using effective direct antiviral agents (DAAs) against chronic hepatitis C (CHC) in Taiwan, the treatment of CHC has been initiated in rural areas. Here, we aimed to elucidate the clinical and virological characteristics of HCV infection, and the treatment efficacy of DAAs in patients from Pingtung county in southern Taiwan. A total of 152 chronic hepatitis patients treated with DAAs were consecutively enrolled. Baseline characteristics and therapeutic efficacy were evaluated. HCV genotype 2 was the most common viral genotype (39.5%), followed by 1b (36.8%), 6 (10.5%), and 1a (9.2%). The sustained virological response (SVR) rate was 98.7%. Hakka patients accounted for 22.4% of the study cohort, of which 14.7% had HCV genotype 6. There were no differences in clinical characteristics between Hakka and non-Hakka patients. Patients with HCV genotype 6 were younger in age (OR/CI: 0.95/0.91-1.00, p = 0.04) and composed of more people who inject drugs (PWID) (OR/CI: 17.6/3.6-85.5, p <0.001), when compared with other patients. We demonstrated that DAA therapy can achieve a 98.7% SVR rate among CHC patients in Pingtung county of southern Taiwan, with a relative higher prevalence of genotype 6. The most important factor attributed to genotype 6 infection was PWID.

Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals.

Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.

Effect of hepatitis C antiviral therapy on oral lichen planus and hyposalivation in inmates.

BackgroundOral lichen planus (OLP) and hyposalivation have been reported as extrahepatic manifestations of hepatitis C virus (HCV) infection. Our study evaluated the effect of direct antiviral agents (DAAs) on OLP and hyposalivation in convicts with chronic hepatitis C, examining patients before, during and after the antiviral treatment period with direct acting antiviral agents (DAAs).MethodsWe screened 198 inmates for the presence of the HCV antibody. Patients found to be positive underwent a quantitative HCV-RNA test and HCV genotype typing, as well as an oral cavity examination using a scoring system for OLP (REU score) and the clinical oral dryness score (CODS). Subsequently, all patients underwent DAA therapy and a systematic physical examination of the oral cavity at 1, 3 and 6 months from the beginning of treatment.ResultsFifty patients (25.25%) had a positive HCV-RNA test. At baseline, OLP was detected in 4 patients (8%), with a mean REU score of 10.13±4, and different degrees of hyposalivation were seen in 17 patients (34%), with a mean CODS score of 4.71±1.72. Six months after the start of DAA therapy, we observed resolution of OLP in 3 patients (75%) and improvement in the remaining subject with a significantly lower mean REU score (2±4). Hyposalivation disappeared in 5 patients, improved in 10, and remained unchanged in 2 patients with a significantly lower mean CODS score (0.06±0.24).ConclusionThis study demonstrated the effectiveness of DAAs in the treatment of OLP and hyposalivation.

Effects of direct antiviral agent on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C

Objective: To explore the effects of direct antiviral agent (DAAs) on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C. Methods: Data of 15 treatment-naive chronic hepatitis C patients and 10 healthy controls were collected. Patients with chronic hepatitis C were treated with DAAs for 12 weeks. Blood samples were collected at 0, 4 and 12 weeks respectively, and blood samples of healthy controls were used as controls. Flow cytometry was used to detect the frequency of classical CD14(++)CD16(-) mononuclear cells and pro-inflammatory CD14(+)CD16(+) mononuclear cells in peripheral blood. Serum sCD14s and sCD163 were detected by enzyme-linked immunosorbent assay. The comparison between the two groups was performed by t-test. The comparison between multiple groups was performed by analysis of variance, and further pairwise comparison was performed by LSD-t test. Results: Prior DAAs treatment, peripheral blood CD14(+)CD16(+) mononuclear cell frequency (18.49% ± 1.54% vs. 10.65% ± 0.83%), serum sCD14s [(64 407.38 ± 5778.49) pg/ml vs. (28 370.76 ± 2 357.68 ) pg/ml] and sCD163 [(22 853.80 ± 4 137.61) pg/ml vs. (2 934.41 ± 223.31) pg/ml] were all higher than healthy controls (P < 0.05), while the frequency of CD14(++)CD16(-) mononuclear cells in peripheral blood was lower than healthy controls (59.14%±0.54% vs. 72.75%±1.31%, P < 0.01). During DAAs treatment, CD14(+)CD16(+) mononuclear cells frequency, serum sCD14 and sCD163 were all decreased significantly. After 12 weeks of treatment, CD14(+)CD16(+) mononuclear cells had decreased to nearly normal level (12.42% ± 1.60% vs. 10.65% ± 0.83%, P > 0.05), and serum sCD14 and scd163 were still higher than those of healthy controls [sCD14: (44 390.06 ± 3 330.17) pg / ml vs. (28 370.76 ± 2 357.68) pg/ml, Scd163: (11 494.79 ± 1 836.97) pg / ml vs. (2 934.41 ± 223.31) pg / ml, P < 0.01], while the frequency of CD14(++)CD16(-)mononuclear cells had gradually increased during the course of treatment and neared healthy control level after 12 weeks of treatment. There was no statistically significant difference between the two groups (71.54) % ± 2.99% vs. 72.75% ± 1.31%, P > 0.05). Conclusion: DAAs therapy can reduce the activation of peripheral blood mononuclear cells in patients with chronic hepatitis C.

Hepatitis C virus-related cryoglobulinemic vasculitis.

Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.

S1053 Risk of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients After Successful Direct Antiviral Agents Therapy

INTRODUCTION: The risk of hepatocellular carcinoma (HCC) associated with chronic hepatitis C infection (HCV) remains a relevant issue in clinical practice. With the direct antiviral agents (DAA) therapy it was expected an indeed strikingly decrease of HCC after sustained virological response (SVR). However, studies have shown discordant results regarding the incidence of HCC in patients with cirrhosis and SVR. Thereby, the aim of the present study was to determine the risk of HCC in a cohort of patients with HCV-related cirrhosis after viral eradication with DAA. METHODS: We collected data retrospectively from HCV patients with liver cirrhosis treated with DAA between January 2015 and December 2019. Individuals with regular compliance to screening program according to EASL guidelines were included in the study. Patients with a previous diagnosis of HCC, non-characterized nodules or without SVR were excluded. RESULTS: A total of 139 cirrhotic patients were included. DAA therapy induced SVR in 92,7% of individuals. Most patients were males (70,5%), with a median age of 56 years old (IQR 52-63) and with prevalent HCV genotype 1 infection (73,4%). In what concerns to severity of liver disease, 105 patients (75,5%) were classified as Child-Pugh class A at the start of DAA therapy. Measurement of liver stiffness (LS) by transient elastography resulted in a median kPa value of 23 (IQR 15-32). The most used treatment regimens were Ledipasvir (LDV)/Sofosbuvir (SOF) (52,5%), LDV/SOF/Ribavirin (16,5%), SOF/Velpatasvir (9,4%) and Elbasvir/Grazoprevir (7,9%). There was a significant decline in LS after antivirals therapy (P < 0.001). HCC was detected in 15 patients (10,8%), within a mean time of 21 months after treatment completion. HCC developed in 7 patients during the first 24 months after finishing antivirals (incidence rate 5,0%) and in additional 8 individuals at longer follow-up (incidence rate 6,1%). 9 patients died, secondary to complications of liver failure (n = 4) or extrahepatic diseases (n = 5). CONCLUSION: DAA are able to eradicate HCV infection in most patients with cirrhosis. Moreover, LS decreases significantly after antiviral treatment. However, the occurrence of HCC is not abolished in effectively treated cirrhotic patients. In fact, HCC may develop not only in the initial period after treatment completion, but there is still a risk of liver cancer later in the follow-up. For these reasons, all cirrhotic patients should be closely monitored and followed after antiviral therapy.Table 1.: Characteristics of hepatitis C infection-related cirrhotic patients who achieved sustained virological response after direct antiviral agents therapy. IQR - interquartile range, LDV – Ledipasvir, SOF – Sofosbuvir, RBV – Ribavirin, VEL – Velpatasvir, EBR – Elbasvir, GRZ – Grazoprevir, GLE – Glecaprevir, PIB – Pibrentasvir, PrOD - Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir

S2656 New Diagnosis of Autoimmune Hepatitis in a Patient With Remote History of SVR From DAA-Based Hepatitis C Treatment

INTRODUCTION: Autoimmune hepatitis (AIH) is characterized by increased aminotransferases, often in the presence of autoantibodies, and biopsy evidence of interface hepatitis. The cause of AIH is not known but it is likely due to a “triggering event” which leads to a T-cell mediated response directed against liver autoantigens. Hepatitis C virus (HCV) and its treatment with direct antiviral agents (DAA) have both has been suspected as risk factors for the development of AIH. We describe a patient with remote history of DAA-cured HCV who later developed decompensated cirrhosis secondary to AIH requiring liver transplantation. This case raises the question as to whether immunologic changes associated with HCV viral clearance are the cause of AIH in some cases. CASE DESCRIPTION/METHODS: A 67-year-old male was referred to our clinic for abnormal liver function tests. He was diagnosed with HCV cirrhosis, treated with 12 weeks of sofosbuvir/ledipasvir and achieved sustained virologic response (SVR). He was well for nearly five years until he developed new-onset ascites and worsening MELD-Na. Acute viral hepatitis serologies for hepatitis A/B/E were negative and HCV RNA levels were undetectable. CT imaging was negative for HCC or thrombus and he denied alcohol use. Smooth muscle IgG antibody was strongly positive and IgG was elevated at 3g/dL; ANA and LKM antibodies were negative. He was on not on any medications traditionally associated with AIH. His liver disease rapidly progressed and he was transplanted without receiving steroids. He is now well post-transplant. Explant biopsy demonstrated interface activity and lobular hepatitis with lymphoplasmacytic inflammation and plasma cells cluster (Figures 1 and 2). DISCUSSION: HCV has been linked to the development of AIH, likely through a process of molecular mimicry whereby the immune system reacts to hepatic autoantigens. While rare, this association has only been documented during active HCV infection or during treatment with DAAs. Our patient had successfully completed treatment for HCV with DAA therapy five years before onset of AIH. We present this case not only to highlight an atypical timeline for development of HCV-induced AIH but to emphasize that providers need to maintain a high index of suspicion for AIH in patients with prior history of HCV treated with DAAs who experience subsequent liver injury.Figure 1.: Low magnification (10x) view of liver section obtained from liver explant, demonstrating interface activity and lobular hepatitis with lymphoplasmacytic inflammation.Figure 2.: Higher magnification (40x) view of the liver section demonstrating plasma cells cluster.

Impact of reimbursement limits on patient access to direct-acting antivirals in Italy: analysis of data from national registries.

Hepatitis C virus (HCV) infection is a global epidemic, still highly prevalent in Europe. Given efficacy and safety of HCV therapy by Direct Antiviral Agents (DAA), World Health Organization called for actions to eliminate HCV infection. A limit is represented by access to care, mostly due to the high costs of medicines. In Italy, in 2015, the access to DAA therapy was reimbursed for patients with advanced disease, whereas in 2017 universal access was granted. The aim of this study was to analyse changes in patient recruitment trends treated with DAA with or without limitations to access to therapy. 165,105 patients treated with DAA in Italy from 2015 to December 2018 were analysed. Daily patient treatment rate was obtained by segmented regression of interrupted time series analysis. 74,199 patients with advanced disease (62% with cirrhosis) had access to the therapy during the time period from 2015 to 2017. Following the extension of reimbursement criteria, 90,906 additional patients were treated (43.2% with F0-F1 and 22.9% with F2), with an absolute reduction of 59.9% of patients with advanced disease (cirrhosis decreased to 18.5%). Segmented regression of interrupted time series analysis of daily patient treatment rate showed a progressive reduction of patients with advanced disease, offset by those with initial disease. Notably, elimination of restrictions to therapy did not change the overall treatment rate. This study showed that a no-limit reimbursement policy for DAAs prescriptions to HCV infected individuals in Italy widened the types of treated patients, but the process towards elimination of HCV infection was not significantly changed.

Changes in Office Blood Pressure Control, Augmentation Index, and Liver Steatosis in Kidney Transplant Patients after Successful Hepatitis C Infection Treatment with Direct Antiviral Agents.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 ± 54 vs. 209 ± 30 dB/m, p < 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy - data from theGerman hepatitis C registry (DHC-R).

Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.