Assessing the rate of non-linkage to care and identifying barriers in individuals living with hepatitis B. Results of the LINK-B study.

BACKGROUND & AIMS: Hepatitis B infection is the most frequent cause of chronic hepatitis and liver cancer worldwide. Active searching for individuals with chronic hepatitis B has been proposed as a strategy to achieve the elimination of this virus. The primary aim of this study was to link to specialists HBsAg-positive individuals detected in a laboratory database and to characterize individuals who were not linked to care. METHODS: We performed a retrospective-prospective evaluation of all HBsAg-positive serum samples identified in the central laboratory of the Northern Barcelona area between January 2018 and June 2022. After reviewing the patients' clinical charts, all those not linked to care were given an appointment with a specialist. RESULTS: Medical records of 2765 different HBsAg-positive serum samples were reviewed and 2590 individuals were identified: 844 (32.6%) were not linked to a specialist, 653 were candidates for linkage, and 344 attended the specialist visit. The two main reasons why they were not under specialist care were administrative issues, such as living in another region (12.1%) and lacking contact details (4.1%), and low life expectancy (2.8%). Individuals who did not attend their scheduled visit were mainly young [38.1 ± 12.9 vs. 44.0 ± 14.0 (p < .001)], non-White European [75.3% vs. 58.1% (p < .001)] and men [70.7% vs. 56.4% (p < .001)]. CONCLUSIONS: One in every three HBsAg-positive individuals in our setting was not currently under specialist care. Of particular note, half of them had never attended a specialist consultation, an essential step for evaluating the disease and starting therapy in some countries.

Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years.

OBJECTIVE: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. METHODS: An economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. RESULTS: SOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197M€. CONCLUSION: SOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Impact of hepatitis D reflex testing on the future disease burden: A modelling analysis.

Chronic hepatitis D (CHD) is a severe form of viral hepatitis that leads to liver cirrhosis and hepatocellular carcinoma. CHD is underdiagnosed, and this study aimed to assess the impact of hepatitis D reflex testing in HBsAg-positive individuals in Spain over the next 8 years. Two scenarios were compared: the current situation (7.6% of HBsAg-positive patients tested for anti-HDV) and reflex testing for all positive samples. A decision tree model was designed to simulate the CHD care cascade. Implementing reflex testing would increase anti-HDV detection to 5498 cases and HDV-RNA to 3225 cases. Additionally, 2128 more patients would receive treatment, with 213 achieving undetectable HDV-RNA levels. The cost per anti-HDV case detected would be €132. In the median time of the analysis, liver complications (decompensated cirrhosis, HCC and liver-related deaths) would be reduced by 35%-38%, implying an estimated cost savings of 36 million euros associated with the management of such complications. By 2030, implementing anti-HDV reflex testing would reduce the clinical and economic burden of CHD by 35%-38%.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels).

BACKGROUND: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Long-term Patient-Centered Outcomes in Cirrhotic Patients With Chronic Hepatitis C After Achieving Sustained Virologic Response.

BACKGROUND & AIMS: Achieving sustained virologic response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis. METHODS: Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry (clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV. RESULTS: Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p < .05 for 16 out of 20 studied PROs]. After achieving SVR and registry enrollment, significant PRO improvements were noted from pre-treatment levels in 11/20 domains for those with DCC (+4% to +21%) and 19/20 PRO domains in patients with CC (+3% to +17%). Patients with baseline DCC had higher rates of hepatocellular carcinoma and mortality (P < .05). In patients with CC, the PRO gains persisted up to 168 weeks (3.5 years) of registry follow-up. In patients with DCC, the improvements lasted for at least 96 weeks but a declining trend after year 2. CONCLUSIONS: Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.

Etiologies and Features of Acute Viral Hepatitis in Spain.

BACKGROUND AND AIM: Etiologies of acute viral hepatitis in high-income countries change with migration of populations, lifestyle changes, and emergence of new pathogens. We analyzed etiologies, characteristics, and outcomes of patients with acute viral hepatitis at a tertiary hospital in Spain. METHODS: We analyzed data from all patients with acute hepatitis (n = 100; 71% male; median age, 42 years; 72% Spanish nationals), older than 16 years, diagnosed in the emergency department of an academic hospital in Barcelona, Spain, from January 2014 through December 2018. Blood samples were collected and patients with serum levels of alanine aminotransferase more than 10-fold the upper limit of normal and markers viral infection were considered to have acute viral hepatitis. We collected clinical information from patients, and samples were analyzed for IgM antibody to hepatitis B (HB) core antigen, HB surface antigen, antibody against hepatitis C virus (HCV), HCV RNA, IgM against hepatitis E virus (HEV), HEV RNA, and IgM against hepatitis A virus (HAV). Patients were followed until resolution of infections or evidence of chronic infection. RESULTS: The most common etiologies of acute hepatitis were HBV infection (28%), HEV infection (18%), HCV infection (17%), and HAV infection (14%). The main risk factors of the cohort were sexual risk contact and intravenous drug use; 79% of cases of HAV had sexual risk behavior. Twenty-nine percent of patients with acute HAV infection and 29% of patients with HBV infection were immigrants to Spain. Fifty-four patients were hospitalized; jaundice and HCV infection were associated with hospital admission. Three patients died (2 from acute liver failure related to acute HBV infection or HBV and HDV co-infection). Chronic infections developed in 5/28 patients (18%) with acute HBV infection and 7/17 patients (41%) with acute HCV infection. CONCLUSIONS: Despite universal vaccination against HBV in Spain, HBV remains the most frequent cause of acute viral hepatitis in our emergency department. Almost one-third of cases of acute HBV and HAV infections were immigrants, possibly from countries with suboptimal vaccination programs. A high proportion of patients with acute hepatitis have HEV infection (18%); acute HAV infection was associated with sexual risk behavior.

Nucleos(t)ide analogue therapy: The role of tenofovir alafenamide.

Chronic hepatitis B virus (HBV) infection remains an important global health problem, and may be difficult to manage in clinical practice. Nucleos(t)ide analogues (NAs) with a high barrier to resistance (entecavir [ETV], tenofovir disoproxil fumarate [TDF] and tenofovir alafenamide [TAF]) are the most frequently used HBV treatments because of their long-term effectiveness and tolerability. ETV may be less effective in patients with lamivudine-resistant strains, and TDF is associated with impaired renal function and reductions in bone mineral density. TAF, a new tenofovir prodrug, has been developed to overcome the less favourable safety profile of TDF. TAF is more stable in plasma, and higher tenofovir levels are achieved within cells at lower doses than with TDF. Several registration and real-life studies, performed up to week 144 of treatment, have shown that TAF is at least as effective as TDF, with higher rates of ALT normalization and significantly fewer kidney disturbances and changes in bone mineral density. No emergence of drug resistance has been found with TAF use. The main limitation to prescribing TAF is its price. The European Association for the Study of the Liver has suggested selecting TAF or ETV instead of TDF in patients >65 years old and in those with a risk of osteoporosis or renal abnormalities, and to prescribe TAF rather than ETV in patients previously exposed to NAs.

Deciphering transplant outcomes of expanded kidney allografts donated after controlled circulatory death in the current transplant era. A call for caution.

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank < 0.001). Besides standard ECD classification, dialysis vintage, older age, and previous cardiovascular recipient events together with low class-II-HLA match, long cold ischemia time and combining a diabetic donor with a cDCD predicted graft loss (C-Index 0.715, 95% CI 0.675-0.755). External validation showed good prediction accuracy (C-Index 0.697, 95%CI 0.643-0.741). Recipient older age, male gender, dialysis vintage, previous cardiovascular events, and receiving a cDCD independently predicted patient death. Benefit/risk assessment of undergoing KT was compared with concurrent waitlisted candidates, and despite the fact that undergoing KT outperformed remaining waitlisted, remarkably high mortality rates were predicted if KT was undertaken under the worst risk-prediction model. Strategies to increase the donor pool, including cDCD transplants with highly expanded donor and recipient candidates, should be performed with caution.

The Screening Guidelines for Hepatitis C Virus Infection as a milestone in the path towards hepatitis C virus elimination.

The publication of the Screening Guidelines for Hepatitis C Virus Infection represents a significant milestone in the path towards eliminating this infectious condition. As early as 2015, the National Health System Plan for Tackling Hepatits C (Plan estratégico para el abordaje de la hepatitis C - PEAHC) pointed out the need to define a screening policy. The Health Ministry has managed to bring together all the actors involved, and to create a technical document that represents a benchmark in the definition of the actions needed to identify and bring treatment closer to a significant number of patients diagnosed with hepatitis C who remain untreated.

Role of Biomarkers in Guiding Cure of Viral Hepatitis B.

Chronic hepatitis B (CHB) virus infection is a global public health threat affecting approximately 257 million individuals worldwide. Hepatitis B surface antigen (HBsAg) loss has been the classic endpoint to define functional cure and decrease the large pool of individuals with CHB. Current treatments with nucleos(t)ide analogues persistently suppress hepatitis B virus (HBV) deoxyribonucleic acid in most CHB patients, but rarely achieve functional cure. New viral biomarkers, such as quantitative HBsAg, hepatitis B core-related antigen, and HBV ribonucleic acid, and combinations of these markers have the potential role of guiding HBV cure by enabling selection of the best candidates for therapy, identifying individuals with a higher likelihood of achieving HBsAg loss, and helping in the design of studies with new drugs. However, some of the assays used to analyze these markers require standardization and improvements in the level of detection. Analysis of host biomarkers to assess the host immune response to HBV is also important, as the natural course of CHB is determined by the interplay between viral replication and the immune response. These biomarkers are, however, in an early phase of development.

Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort. METHODS: We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset. RESULTS: The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) [total, with or without cirrhosis]). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038). CONCLUSION: In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF. LAY SUMMARY: In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.

Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.

Unexpected long-lasting anti-HEV IgM positivity: Is HEV antigen a better serological marker for hepatitis E infection diagnosis?

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. The minimum criterion for diagnosis of acute infection is detection of anti-HEV antibodies, although there are scant data on IgM duration. Our aim was to assess the persistence of HEV markers after acute self-limited hepatitis E. HEV serological tests (IgM by Mikrogen and Wantai and HEV-Ag) and HEV RNA were carried out in two cohorts: (a) patients with prior acute hepatitis E (ALT >10 x ULN plus positive IgM ± HEV RNA) currently self-limited and (b) 50 blood donors with positive HEV RNA. Among 25 cases of prior acute hepatitis E, after a median follow-up of 34 months, all presented undetectable HEV RNA. However, anti-HEV IgM remained detectable in 14 (56%) by Mikrogen, 6 (24%) by Wantai and none for HEV-Ag. Anti-HEV IgM tested positive in 80%-100% within the second year and 17%-42% over 3 years later, by Wantai and Mikrogen, respectively. Among HEV RNA-positive donors, 12 (25%) tested positive for either IgM by Mikrogen or Wantai, 9 (18%) for both and 18 (36%) for HEV-Ag. HEV-Ag positivity was more likely as HEV RNA was higher (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7). Overall, HEV-Ag performed best, with a positive predictive value of 100% and diagnostic accuracy of 57%. Anti-HEV IgM exhibited unexpectedly long persistence after a self-limited acute hepatitis E. HEV-Ag had the best performance and could be especially useful in settings where HEV RNA is not available.

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues.

Management of chronic hepatitis B (CHB) is still considered a challenge in clinical practice. Patients must be carefully evaluated before starting therapy. This includes virology and laboratory assessments, an estimation of fibrosis by invasive and/or noninvasive methods, and an estimation of the risk of hepatocellular carcinoma (HCC). Nucleos(t)ide analogues (NAs) with a high barrier to resistance (tenofovir disoproxil fumarate [TDF], entecavir [ETV] and tenofovir alafenamide [TAF]) are the most frequently used treatments because of their good long-term efficacy and tolerability. None of these options has been shown to be more effective than the other, but certain factors should be considered when selecting the best therapy for specific populations. Most patients achieve a virological and biochemical response to these agents, with a low rate of emerging resistance during long-term treatment. However, the rate of hepatitis B surface antigen (HBsAg) loss is low and in most cases NAs therapy is lifelong. Safety concerns for long-term NA use have become a priority in the management of CHB, in particular, the risk of impaired kidney function and bone marrow density loss described with TDF regimens. The risk of HCC is not completely eliminated by NAs. Thus, patients at higher risk should be identified and provided with appropriate surveillance.

Immune-related hepatitis related to checkpoint inhibitors: Clinical and prognostic factors.

BACKGROUND & AIMS: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). METHODS: This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. RESULTS: Twenty-eight cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001). CONCLUSIONS: Immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.

Management of chronic liver disease-associated severe thrombocytopenia in Spain: a view from the experts.

BACKGROUND: chronic liver disease (CLD) patients often present thrombocytopenia (TCP) and when severe, it may prevent them from undergoing necessary invasive procedures due to an increased bleeding risk. The lack of scientific evidence makes it impossible to determine key aspects of the current management and associated healthcare burden of these patients in Spain. PURPOSE: to gain insight into the current situation of patients with CLD-associated severe TCP undergoing invasive procedures in Spain, based on the experience of clinical experts. METHODS: national Delphi study involving 32 medical experts. RESULTS: the estimated prevalence of CLD-associated severe TCP is approximately 5,967, with an annual incidence of 1,148 new patients. Patients undergo a median of 1 (0-3) invasive procedures/year. Platelet transfusions (PTs) are the standard option to raise platelet counts and are associated with significant burden. The achievement of target platelet levels (≥ 50 x 109/l) after a transfusion is not routinely measured. The lack of effectiveness and short life span of transfused platelets can lead to procedure cancellations and bleeding events, which potentially affect patient outcomes. Adverse events occur in 1-25 % of patients, including mild (febrile and allergic reactions) and severe events (e.g., transfusion-related acute lung injury). Between 5-15 % of patients are unfit to receive PTs and approximately 3 % are treated off-label with thrombopoietin receptor agonists. CONCLUSIONS: this study provides a snapshot of the current situation in Spain, highlighting that the current management is poorly standardized and suboptimal in some cases. The results suggest the benefit of developing a consensus document to address some of these shortcomings and to advance in the search for alternatives to PTs.

Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020). / Documento de consenso de la Asociación Española para el Estudio del Hígado sobre el tratamiento de la infección por el virus de la hepatitis B (2020).

Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.

Treating chronic hepatitis delta: The need for surrogate markers of treatment efficacy.

Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible "trial endpoints") that could be used across different clinical trials.

Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis.

BACKGROUND & AIMS: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis. METHODS: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events. RESULTS: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir. CONCLUSIONS: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis. LAY SUMMARY: Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.