Recurrent Hepatitis Research Articles

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

SummaryImmune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta-Analyses Supporting American Association for the Study of Liver Diseases Guidelines.

Three key management decisions in autoimmune hepatitis concern the use of budesonide and azathioprine as first-line therapy, the choice of mycophenolate mofetil or calcineurin inhibitors for patients failing steroids and azathioprine, and the role of maintenance steroids in prevention of recurrence after liver transplantation. To address these questions, comprehensive searches were performed (without language restrictions) of several databases from their inceptions to January 8, 2019. From 1,712 citations identified, the full texts of 578 studies were reviewed, and 13 studies met criteria for systematic review. Budesonide and azathioprine were significantly superior to prednisone and azathioprine in normalizing serum aminotransferase levels after 6 months in non-cirrhotic adults (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.3-3.67). However, the evidence for other outcomes was of low quality. Overall, differences in endpoint criteria and insufficiencies in data analyses precluded confident conclusions about superiority of treatment regimens. There were no significant differences in the frequencies of biochemical remission in patients with an inadequate response or intolerance to steroids and azathioprine after treatment with mycophenolate mofetil or tacrolimus (OR, 1.95; 95% CI, 0.18-20.81). The frequencies of composite outcomes of death and liver transplantation were similar for both regimens (OR 1.70; 95% CI, 0.56-3.37). The frequencies of recurrent autoimmune hepatitis after liver transplantation were also similar, regardless of whether steroids were withdrawn or continued (OR 0.27; 95% CI 0.01-7.25). Conclusions: First-line treatment with budesonide and azathioprine normalizes serum aminotransferase levels more often than prednisone and azathioprine after six months in non-cirrhotic adults. Its effectiveness in treating other presentations or reducing either mortality or need for liver transplantation remains unproven. The frequencies of biochemical remission induced by mycophenolate mofetil or tacrolimus for treatment failure or drug intolerance were comparable. Continuation of steroid therapy does not prevent recurrence post-transplant. Future studies are essential to generate evidence-based therapeutic recommendations for autoimmune hepatitis.

The use of Ingaron® in the treatment of chronic viral hepatitis B

The possibility of antiviral therapy with the direct antiviral drugs Entecavir and Ingaron, as an antiviral and immunomodulating therapy, was studied in patients with the recurrent chronic viral hepatitis B. The study showed the applicability of this treatment regimen, due to the increase in the number of patients with SVR, high tolerability and the absence of clinically significant side effects.

Japan Society of Hepatology guidelines for the management of hepatitis C virus infection: 2019 update.

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the Committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the Committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.

Shear Wave Elastography Performance in Noninvasive Assessment of Liver Cirrhosis in Liver Transplant Recipients With the Recurrence of Hepatitis C Infection

BackgroundThe recurrence of hepatitis C (HCV) after liver transplant (LTX) leads to graft fibrosis and cirrhosis. Liver biopsy remains the criterion standard for their diagnosis and monitoring. Our objective was evaluation of shear wave elastography (SWE) in patients with HCV recurrence after LTX and its comparison with histopathologic fibrosis assessment scoring systems. MethodsA total of 101 LTX recipients with HCV recurrence (42 women [41.6%] and 59 men [58.4%]) were evaluated by graft biopsy specimens (Ishak, Scheurer, and meta-analysis of histologic data in viral hepatitis [Metavir] score) and SWE (liver stiffness). Median age of patients was 59.4 years; median time from LTX was 84.9 months. The study protocol conforms with the Declaration of Helsinki. ResultsMedian liver stiffness was 21.3 kPa. To differentiate between liver fibrosis and cirrhosis, patients were divided into 2 subgroups: Ishak score fibrosis (1-4 [85.2%]) and cirrhosis (5-6 [13.9%]); Scheurer score fibrosis (0-3 [85.2%]) and cirrhosis (4 [12.9%]); Metavir score fibrosis (0-3 [85.2%]) and cirrhosis (4 [14.9%]). We have observed statistically significant differences between liver fibrosis and liver cirrhosis groups defined on the basis of Ishak, Scheurer, and Metavir scoring systems: 20.8 kPa vs 29.6 kPa (P = .001), 20.7 kPa vs 30.3 kPa (P = .0005), and 20.7 kPa vs 28.8 kPa (P = .002), respectively. ConclusionsOur results indicate that SWE may be useful in differentiating patients with advanced cirrhosis from those with fibrosis and may be helpful in the noninvasive diagnosis and monitoring of HCV recurrence after LTX.

Circulating exosome DANCR correlated to the recurrence of hepatitis C virus-related hepatocellular carcinoma.

e13688 Background: Long non-coding RNAs (lncRNAs) have been associated with various types of neoplasms. Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) has high risk of recurrence. Methods: Differentially-expressed candidate lncRNAs relevant to HCV-HCC were identified by RNA-seq in Screening set, validated by qPCR in Validation set, and confirmed in external Test cohort. Target lncRNAs in tissue and serum exosome were applied to predict HCC recurrence of HCV-HCC after curative surgical resection in a large Application cohort. Pathogenetic mechanisms of target lncRNA were explored by using JFH1-infectious cells. Results: Of the top ten differentially-expressed lncRNAs relevant to HCV-related HCC identified in Screening set, differentiation antagonizing non-protein coding RNA (DANCR), which was upregulated by HCV infection and identified as the most relevant lncRNA to HCV-HCC, was overexpressed in tumor than in adjacent non-tumor (ANT) tissues. Of 183 HCV-HCC patients followed for 10 years after curative HCC resection, tumor DANCR, tumor/ANT DANCR ratio and circulating exosome DANCR levels were positively associated with HCC recurrence. Circulating exosome DANCR levels by droplet digital PCR provided the best predictive power of HCC recurrence with area under the curve of 0.88, when compared to tumor DANCR levels, tumor/ANT DANCR ratio, and alfa-fetoprotein. Exosome DANCR > 50 copies/ml was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively, Cox regression model). Cell experiments showed that DANCR, positively associated with mesenchymal-associated β-catenin expression, promoted cell migration and invasion ability. Conclusions: lncRNA-DANCR was highly relevant to disease progression of HCV-HCC. Circulating exosome DANCR could serve as a non-invasive prognostic biomarker for HCV-HCC.

JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update;Protective Effect of Antiviral Therapy against Hepatocarcinogenesis.

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.

SUN-508 Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease

Title: Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease Introduction: The association between Graves’ disease and coexisting autoimmune hepatitis is well known. Treatment of autoimmune hepatitis with glucocorticoids can concurrently lower thyroid hormone levels. Additionally, recurrence of hyperthyroidism has been shown to be associated with recurrence of autoimmune hepatitis. We present a case of a patient with autoimmune hepatitis and Graves’ thyrotoxicosis, which initially improved with prednisone therapy, but thyrotoxicosis recurred during the prednisone taper while hepatitis stayed in remission. Clinical Case: A 47-year old female initially presented with fatigue, nausea, and jaundice. Liver enzymes showed elevated AST (1634 U/L) and ALT (1956 U/L) with total bilirubin 15.1 mg/dL. Liver biopsy was consistent with autoimmune hepatitis. Treatment was initiated with ursodiol 300 mg TID and liver enzymes improved to ALT 579 IU/L and AST 544 IU/L with total bilirubin 1.9 mg/dL. Nine months later, she presented with worsening upper and lower extremity weakness, slurred speech, abdominal pain, and nausea and vomiting. AST and ALT were again elevated to >1,000 U/L. TFTs were checked due to symptoms of palpitations and heat intolerance. TSH was 0.024 uIU/mL with elevated free T4 of 3.74 ng/dL and TSI of 435%. She was treated with prednisone, cholestyramine, and propranolol and discharged with a one-month prednisone taper starting at 60 mg daily. LFTs and TFTs normalized after one month. Cholestyramine was discontinued and prednisone was tapered to 5 mg daily. Seven months later, she had symptoms of palpitations and heat intolerance. TFTs were consistent with hyperthyroidism (TSH 0.049 uIU/mL, free T4 3.96 ng/dL). LFTs remained in normal range. Since thionamides have relative contraindications in patients with liver disease, prednisone was increased from 5 mg to 20 mg daily and cholestyramine was resumed to treat hyperthyroidism. After five months, TSH remained suppressed to 0.019 uIU/mL however free T4 improved to 1.74 ng/dL. The patient was referred for total thyroidectomy. Conclusion: This case illustrates an example of the rarely reported occurrence of thyrotoxicosis recrudescence despite initial improvement with treatment of underlying autoimmune hepatitis. Recognition of recurrence of hyperthyroidism independent of recurrence of autoimmune hepatitis indicates the need for early definitive therapy for hyperthyroidism.

Renal safety of tenofovir disoproxil fumarate and entecavir with hepatitis B immunoglobulin in liver transplant patients.

Potent nucleos(t)ide analogues and hepatitis B immunoglobulin combinations are recommended after liver transplantation to prevent the recurrence of hepatitis B virus (HBV). Despite its proven efficacy, the renal safety of tenofovir disoproxil fumarate (TDF) has not been well established in liver transplant recipients. We aimed to assess the impacts of TDF and entecavir (ETV) on tubular and glomerular functions. We analysed 206 liver transplant patients treated with TDF (n=102) or ETV (n=104) plus hepatitis B immunoglobulin. Serum creatinine, phosphate and uric acid levels were measured. Proximal tubular dysfunction was defined as the presence of hypophosphatemia (<2mg/dL) and hypouricemia (<2mg/dL). Glomerular dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60mL/min/1.73m2 accompanied by a ≥25% eGFR decline from baseline. During a median follow-up of 42.5months, 48 patients developed proximal tubular dysfunction (30.4% and 16.3% in the TDF and ETV groups; P=.017). Serum levels of phosphate and uric acid were significantly lower in the TDF group post-LT. TDF (OR, 2.34; 95% CI, 1.16-4.69; P=.017) and low body mass index (OR, 2.11; 95% CI, 1.06-4.21; P=.034) were independent risk factors for proximal tubular dysfunction. The prevalence of glomerular dysfunction was not significantly different between the two groups (TDF 51.0% and ETV 54.8%; P=.582). TDF significantly increased the risk of proximal tubular dysfunction. Although the effect of TDF on glomerular function was comparable to that of ETV, glomerular dysfunction was common after liver transplant.

Prophylaxis of Hepatitis B Virus (HBV) Re-Infection in Liver Transplantation: Is the Reappearance of Hepatitis B Surface Antigen (HBsAg) Significant?

The recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) was in the past a primary cause of organ loss or mortality. Currently, post-OLT prophylaxis with anti-HBs immunoglobulins plus a nucleos(t)ide analogue has virtually abolished the risk of re-infection. Some studies have proposed to simplify prophylaxis by discontinuing immunoglobulins while continuing the analogue alone.This review analysed the available studies, focusing on the recurrence of HBsAg in serum and its biological effects. In all, 16 studies were retrieved, mainly observational or retrospective, each enrolling 14 to 80 patients. Our review of the literature found that HBsAg re-appeared in 0% to 24% of the patients, generally with HBV DNA undetectable in plasma. One study measured HBsAg using a new ultra-sensitive method, which could allow a reappraisal of the incidence of recurrence. This review discusses the role of HBV surface proteins in inducing hepatocellular carcinoma, particularly when mutations in the C-terminal occur that induce stop-codons that cause defects of secretion and retention of truncated protein S, resulting in direct cell toxicity and cancer. The data on the suspension of immunoglobulins in the prophylaxis regimes of post-transplant re infection do not appear sufficiently robust for an extensive and safe application in clinical practice.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of Solid-Organ Transplants.

Evaluation of Different Regimens of New Direct Acting Antiviral drugs (DAAs) for treatment of Recurrent Hepatitis C Virus Infection after Liver Transplantation

Abstract Aim of the work To compare between different available regimens of DAAs (sofosbuvir/ daclatasvir and sofosbuvir / ledipasvir) regarding the efficacy and safety for treatment of compensated recurrent hepatitis C Virus infection after liver transplantation in Egyptian patients and to study the correlation between sofosbuvir / daclatasvir and sofosbuvir / ledipasvir and post-transplant complications. Background Liver transplantation is the only curative treatment for ESLD and HCC. Liver disease resulting from chronic HCV infection is the leading indication for liver transplantation. For patients with detectable HCV-RNA levels at the time of transplantation, postoperative recurrence of HCV infection was “immediate and universal.” Recurrent HCV infection follows an aggressive course and retransplantation frequently is associated with a poor outcome. Patients and Methods This prospective study was conducted on recipients, who underwent living donor liver transplantation in Ain Shams Center for Organ Transplantation (ASCOT) at Ain Shams University Specialized Hospital (ASUSH), Cairo, Egypt between June, 2016 and May, 2017. Data of the recipients, who underwent living donor liver transplantation during the study period, were reviewed and the patients who fulfilled the inclusion criteria were enrolled into this study. The patients who fulfilled the inclusion criteria and received antiviral treatment were followed up monthly during their treatment and after finishing treatment for at least 3 months. Results Treatment of HCV recurrence in liver transplant recipients with SOF+DCV+RBV or SOF/LDV+RBV seems to confer high rates of SVR. There was no difference between both regimens regarding adverse events. Prolonged treatment of HCV recurrence after LDLT (24 weeks) was significantly associated with a higher SVR (P = 0.035). Conclusion Adding RBV to antiviral regimens in the treatment of HCV recurrence in liver transplant recipients doesn’t seem to add to the efficacy of DAAs. Adherence to prolonged course of antiviral treatment (6 months) when treating HCV recurrence post liver transplantation seems to be associated with higher rates of SVR than shorter course (3 months) with no increase in the incidence of adverse events or rejection episodes.

Platelet activation during chronic hepatitis B infection exacerbates liver inflammation and promotes fibrosis.

Recurrent hepatitis activity during chronic hepatitis B virus infection results in fibrosis and even hepatocellular carcinoma. It is still unclear what causes acute exacerbation. As platelets have recently been identified as a significant role in inflammation, we here investigated the role of platelets in mediating liver damage in patients with chronic hepatitis B virus infection. Platelet aggregation testing and flow cytometry were carried out to evaluate platelet activation status in 121 patients chronically infected with hepatitis B across different phases of the condition. The correlation between platelet aggregation rate and liver inflammation or liver fibrosis index was evaluated. To investigate the genesis of platelet activation, several serum cytokines were also assessed by MILLIPLEX microsphere-based multiplex cytokine assay. Active hepatitis patients showed a higher aggregation rate than others. Levels of CD62p, a marker of platelet activation, were also increased in this group of patients. Positive correlations between platelet aggregation rate and liver inflammation or liver fibrosis were also noted, indicating a significant role of platelet in the progression of liver disease. The level of tumor necrosis factor-alpha, which is known to trigger platelet activation, was markedly higher in the active hepatitis group (P < .005). Based on the findings in our study, platelet activation plays a vital role in the progression of chronic hepatitis B virus infection. Antiplatelet therapy may provide a new means of hepatitis B infection treatment.

Recurrent Disease After Liver Transplantation

Liver transplantation is an effective treatment for many different types of acute and chronic liver disease. Many diseases recur following liver transplantation. This review provides an update in the latest clinical developments in recurrent disease after liver transplantation. Low-dose corticosteroids are associated with a reduction in recurrent autoimmune hepatitis following liver transplantation. “De novo” autoimmune hepatitis should be considered and treated as a form of allograft rejection. Tacrolimus has been reported to increase the risk of recurrent primary sclerosing cholangitis following liver transplantation. Autoimmune liver diseases such as primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis notably recur after transplant although the clinical significance of recurrent disease remains unclear. The clinical presentation, diagnosis, and management of recurrent autoimmune liver disease are variable and retransplantation is uncommonly needed. With the indications for liver transplantation constantly expanding, recurrence of original disease remains an important topic requiring further study.

The Reliability of Fibro-test in Staging Orthotopic Liver Transplant Recipients with Recurrent Hepatitis C.

Background and Aims: Liver biopsy remains the gold standard for staging of chronic liver disease following orthotopic liver transplantation. Noninvasive assessment of fibrosis with Fibro-test (FT) is well-studied in immunocompetent populations with chronic hepatitis C virus infection. The aim of this study is to investigate the diagnostic value of FT in the assessment of hepatic fibrosis in the allografts of liver transplant recipients with evidence of recurrent hepatitis C.Methods: We retrospectively compared liver biopsies and FT performed within a median of 1 month of each other in orthotopic liver transplantation recipients with recurrent hepatitis C.Results: The study population comprised 22 patients, most of them male (19/22), and with median age of 62 years. For all patients, there was at least a one-stage difference in fibrosis as assessed by liver biopsy compared to FT, while for the majority (16/22) there was at least a two-stage difference. The absence of correlation between the two modalities was statistically demonstrated (Mann-Whitney U test, p = 0.01). In detecting significant fibrosis (a METAVIR stage of F2 and above), an FT cut-off of 0.5 showed moderate sensitivity (77%) and negative predictive value (80%), but suboptimal specificity (61%) and positive predictive value (58%).Conclusions: In post-transplant patients with recurrent hepatitis C, FT appears to be inaccurately assessing the degree of allograft fibrosis, therefore limiting its reliability as a staging tool.

Retrospective study of the outcome of liver transplantation in Egyptian patients with chronic hepatitis C virus infection

Aim To assess the outcome of living-related-donor liver transplantation for chronic hepatitis C infection in Egyptian patients including hepatitis C recurrence, fibrosis progression, and improved survival. Patients and methods This retrospective study included 104 adult Egyptian patients with chronic liver disease due to chronic hepatitis C, who underwent living-donor liver transplantation at Wadi El-Neel Hospital, Cairo, Egypt, during the period from January 2005 to January 2014. All data regarding comprehensive history taking, clinical examination, laboratory evaluation, model for end-stage liver disease score, fibrosis-4 score, liver biopsy, histopathology examination, and radiological evaluation before and after transplant were collected and analyzed. Moreover, the data of regimen of immunosuppression and regimen of antiviral therapy after transplant were collected and analyzed. Results There were 75 males and 29 females. Their ages ranged from 30 to 74 years, with an average of 51.62 years old. Of 104 cases, 90 were of class C, whereas 13 cases of class B, and only one case was class A Pugh–Child classification. Of 104 cases, 31 missed follow-up owing to follow-up in another hospital within their city. Recurrence of hepatitis C virus infection after liver transplantation occurred in 73 (70.19%) cases. Sustained virological response was observed in 40 (54.79%) cases, and relapse was observed in 33 (31.73%) cases after antiviral treatment. Second relapse after treatment occurred in 33 (31.73%) of 73 cases and received antiviral therapy course again, with sustained virological response in 15 (45.45%) cases out of 33, relapse again was seen in seven (21.21%) of 33 cases, and 11 (42.4%) of 33 cases were nonresponders. According to clinical outcomes in the studied cases, eight (7.7%) died, five (4.8%) cases had decompensated liver disease, five (4.8%) cases underwent retransplantation, two (19%) cases had liver fibrosis, and one case (0.96%) had hepatocellular carcinoma.

Retraction: Pathological Roles of Interleukin-22 in the Development of Recurrent Hepatitis C after Liver Transplantation.

Retraction: Pathological Roles of Interleukin-22 in the Development of Recurrent Hepatitis C after Liver Transplantation.

Modelling Recurrent Primary Biliary Cholangitis and Primary Sclerosing Cholangitis as Infectious Diseases Following Liver Transplantation

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are idiopathic and progressive autoimmune hepatobiliary disorders that lead to liver failure and a need for liver transplantation in a proportion of individuals with poorly controlled disease. It is currently thought that an environmental agent triggers disease in a genetically susceptible host and to date, xenobiotics, bacteria and a human betaretrovirus have all been linked with PBC. However, there is no consensus on which agents predominates. These disease processes are poorly understood and there are disparate hypotheses concerning the pathogenesis. One theory suggests that the disease is mediated by autoimmunity, whereas others have speculated that they are infectious disease processes that only manifests in individuals with diminished immunity. Clinically, the triggers of disease are difficult to study because of the indolent onset and chronic nature of the disorders. Notably, observations from liver transplantation provide a unique insight into the development of PBC and PSC. Both biliary disorders may reoccur in up to 30%-50% of patients following liver transplantation and many of the factors that influence recurrence have been well described. Prior to transplantation, immunosuppression is not routinely used to treat PBC and PSC because specific treatments have not been shown to have utility or have caused undue side effects. Following transplantation, recurrence occurs earlier and tends to be more aggressive in those treated with more potent immunosuppressive agent such as tacrolimus as compared to cyclosporine, which also has broad antiviral activity. The development of cholestasis within the first year following liver transplantation was found to be predictive of recurrence years later, a finding that parallels observations in patients with recurrent viral hepatitis following liver transplantation. Herein, we discuss the observations from liver transplant recipients with recurrent autoimmune liver disease and model our findings in comparison with patients that develop recurrent infectious disease. These studies help provide a framework and understanding of the processes associated with autoimmune liver diseases in general.

PIN2 EFFECTIVENESS AND SAFETY OF DIRECT-ACTING ANTIVIRALS FOR HEPATITIS C VIRUS INFECTED PATIENTS AFTER LIVER TRANSPLANTATION. RESULTS IN REAL CLINICAL PRACTICE.

Recurrent hepatitis C virus (HCV) infection is observed after liver transplantation (LT) among HCV-infected patients. Clinical trials have displayed that direct-acting antivirals (DAAs) have increased response and safety rate across different HCV-infected patient populations, including LT recipients. The objective is to evaluate real-life effectiveness and safety of DAAs therapy in HCV-infected LT recipients. Prospective, observational study in HCV-infected patients undergoing LT, who initiated DAAs treatment from 2015 to 2018. Exclusion criteria: patients from penitentiary centers, pediatrics, hepatic retransplatation. Effectiveness main variable: sustained virological response 12 weeks post-treatment (SVR12). Safety variable: treatment withdrawal secondary to severe adverse events. Covariates: gender, age, HIV coinfection, previous treatment, hepatic transplantation, cirrhosis, fibrosis, viral genotype, baseline viral load and antiviral treatment. Statistical method: intention-to-treat descriptive analysis, comparing LT patients with no-LT patients. Statistical signification calculated with Fisher exact or Mann-Whitney tests. Study authorised by the Health System Investigation Committee. 1313 patients were included, 43 of them LT-recipients: 69.7% males; 61.7 years mean age; 67.1% genotype 1; 11.7% cirrhotics (F4), 11.6% F3 fibrosis grade, 32.6% F2; 41.9% with hepatocellular carcinoma; 44.9% HCV-treatment-experienced; 42.1% null-responders and 21.1% recidivants to previous treatments; 62.8% treated with ledispasvir/sofosbuvir±ribavirin; 48.9% treatment length for 12 weeks and 48.9% for 24 weeks. A high treatment-experienced patients rate was observed in LT-recipients vs no-LT-recipients (44.2% vs 24.5%; p=0.006); similar genotype or fibrosis grade in both cohorts (p>0.05). Effectiveness results in LT-recipients vs no-LT-recipients: 0.00% vs 1.26% recidivants (p=0.97); 0.00% vs 0.31% null-responders (p=0.30); 100.0% vs 96.06% SVR12 (p=0.36). No patient experimented treatment withdrawal in both cohorts (LT-recipient or no-LT-recipient) due to severe adverse events (p>0.99). DAAs are safe and effectives in the treatment of recurrent HCV infection after liver transplantation, even with unfavorable baseline response factors, as previous antiviral treatment. Results are very similar to those observed among no-LT-recipients.

Toward Zero Hepatitis C Virus-Related Mortality as a Prerequisite for the Release of Resources in a Center for Follow-up of Liver Transplant

Taking charge of a liver transplanted (LT) patient implies not only to follow up the transplanted organ (eg, immunosuppression and cancer risk) but also to deal with the prevailing patient’s active problems.The recurrence of hepatitis C on the graft has historically been one of the main active problems to be addressed, leading to 30% to 40% mortality per se in these patients and has involved many resources in the hepatological centers responsible for the follow-up.We verified how much the availability of the new drugs with direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) has impacted the mortality within the assisted population, changing its characteristics and addressing new clinical issues in the LT-patients.We performed a retrospective comparison between 230 LT patients followed up during pre-DAA era (group 1, with 88 HCV RNA-positive) and 244 patients observed from 2014 onward when DAAs became available (group 2, with 79 HCV RNA-positive).Fifty-two antiviral therapies were performed in group 1 with 18 sustained virologic response (SVR) (35%) and 53 treatments, of which 37 were retreatments, in group 2 with 51 SVR (96%), P = .0001. Deaths for HCV-related causes were 19 of 33 (57%) in group 1 and 7 of 24 (24%) in group 2, P = .01. The Kaplan-Meier showed a dramatic reduction in excess mortality in HCV-LT patients after the availability of DAAs.These results suggest that HCV is no longer the main active problem of follow-up in liver transplants, therefore the resources can be relocated to take care of other clinical aspects.