Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C.

INTRODUCTION AND OBJECTIVES: Cause of mortality in patients with chronic liver diseases (CLDs) may differ based on underlying etiology of liver disease. Our aim was to assess different causes of death in patients with the most common types of CLD using a national database from the United States. MATERIALS AND METHODS: Death data from 2008 and 2018 from the National Vital Statistics System (NVSS) by the National Center for Health Statistics (NCHS) were used. The rank of cause-of-death for each etiology of CLDs was assessed. Causes of death were classified by the ICD-10 codes. Liver-related deaths included liver cancer, cirrhosis and CLDs. RESULTS: Among a total of 2,826,531 deaths in 2018, there were 85,807 (3.04%) with underlying CLD (mean age at death 63.0 years, 63.8% male, 70.8% white). Liver-related mortality was the leading cause of death for all types of CLD [45.8% in non-alcoholic fatty liver disease (NAFLD), 53.0% in chronic hepatitis C (CHC), 57.8% in chronic hepatitis B (CHB), 81.8% in alcoholic liver disease (ALD)]. This was followed by death from cardiac causes (NAFLD 10.3%, CHC 9.1%, CHB 4.6%, ALD 4.2%) and extrahepatic cancer (NAFLD 7.0%, CHC 11.9%, CHB 14.9%, ALD 2.1%). Although liver cancer was the leading cause of cancer death, lung, colorectal and pancreatic cancer were also common causes of cancer death. CONCLUSIONS: Among deceased patients with CLD, underlying liver disease was the leading cause of death. Among solid cancers, liver cancer was the leading cause of cancer-related mortality.

Australia could miss the WHO hepatitis C virus elimination targets due to declining treatment uptake and ongoing burden of advanced liver disease complications.

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia's progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

Changes in clinical scenarios, management, and perspectives of patients with chronic hepatitis C after viral clearance by direct-acting antivirals.

INTRODUCTION: Hepatitis C virus (HCV) causes a systemic infection inducing hepatic and extrahepatic diseases. These latter involve cardiovascular system, kidney, brain, endocrine, glucose, and lipid metabolism, and the immune system. HCV infection is associated with an increased risk of morbidity and mortality for both hepatic and extrahepatic events. Direct-acting antivirals (DAA), introduced in the most recent years for HCV treatment, are effective in up to 99% of cases and have changed the clinical scenarios and management of these patients. AREAS COVERED: The literature on the impact of HCV clearance by DAA on both hepatic and extrahepatic disease outcomes has been analyzed and discussed in this review in order to summarize the full therapeutic potential and its weaknesses. EXPERT OPINION: Patients achieving HCV clearance have improved hepatic and extrahepatic diseases, quality of life and survival. They have lower incidence of cardiovascular disease, type 2 diabetes, kidney damage, and immuno-mediated manifestations. However, the improvements are related to the degree of pre-treatment organ damage. Therefore, a significant percentage of patients with advanced disease remains at risk of morbidity and mortality and must be monitored in the post-treatment. In addition, data emphasize the importance of starting treatment during the early stages of HCV infection.

Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study.

BACKGROUND: Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan. METHODS: A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT). RESULTS: The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child-Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child-Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl. CONCLUSIONS: Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

Alcohol Intake and Mortality in Patients With Chronic Viral Hepatitis: A Nationwide Cohort Study.

INTRODUCTION: We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. METHODS: A total of 364,361 men and women aged 40-84 years who underwent health screening examination between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. RESULTS: In participants without chronic viral hepatitis, the fully adjusted hazard ratios (HRs) for all-cause mortality comparing light, moderate, and heavy drinkers with nondrinkers were 0.92 (95% confidence interval [CI] 0.87-0.98), 1.08 (95% CI 1.01-1.16), and 1.51 (95% CI 1.33-1.72), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.19 (95% CI 1.05-1.36), 1.23 (95% CI 1.06-1.43), and 1.69 (95% CI 1.28-2.24), respectively (P value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared with participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 10.85, 95% CI 9.74-12.09) and extrahepatic cancer mortality (HR 1.37, 95% CI 1.26-1.49). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. DISCUSSION: Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.

Cost-effectiveness analysis of chronic hepatitis C treatment in the prison population in Spain.

OBJECTIVES: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. MATERIAL AND METHOD: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. RESULTS: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. DISCUSSION: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management.

Alcohol use disorders and the risk of progression of liver disease in people with hepatitis C virus infection - a systematic review.

Liver cirrhosis and other chronic liver diseases are usually compartmentalized into separate categories based on etiology (e.g., due to alcohol, virus infection, etc.), but it is important to study the intersection of, and possible interactions between, risk factors. The aim of this study is to summarize evidence on the association between alcohol use disorders (AUDs) and decompensated liver cirrhosis and other complications in patients with chronic Hepatitis C virus (HCV) infection. A systematic search of epidemiological studies was conducted using Ovid Medline databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Relative Risk estimates were combined using random-effects meta-analyses. The proportion of cases with liver disease progression that could be avoided if no person with a chronic HCV infection had an AUD was estimated using an attributable fraction methodology. A total of 11 studies fulfilled the inclusion criteria, providing data from 286,641 people with chronic HCV infections, of whom 63,931 (22.3%) qualified as having an AUD. Using decompensated liver cirrhosis as the outcome for the main meta-analysis (n = 7 unique studies), an AUD diagnosis was associated with a 3.3-fold risk for progression of liver disease among people with a chronic HCV infection (95% Confidence Interval (CI): 1.8-4.8). In terms of population-attributable fractions, slightly less than 4 out of 10 decompensated liver cirrhosis cases were attributable to an AUD: 35.2% (95% CI: 16.2-47.1%). For a secondary analyses, all outcomes related to liver disease progression were pooled (i.e., liver deaths or cirrhosis in addition to decompensated liver cirrhosis), which yielded a similar overall effect (n = 13 estimates; OR = 3.7; 95% CI: 2.2-5.3) and a similar attributable fraction (39.3%; 95% CI: 21.9-50.4%). In conclusion, AUDs were frequent in people with chronic HCV infections and contributed to worsening the course of liver disease. Alcohol use and AUDs should be assessed in patients who have liver disease of any etiology, and interventions should be implemented to achieve abstinence or to reduce consumption to the greatest possible extent.

Mortality from liver diseases attributable to hepatitis B and C in the EU/EEA - descriptive analysis and estimation of 2015 baseline.

Background: WHO has set target to reduce mortality attributable to hepatitis B (HBV) and hepatitis C (HCV) by 65% by 2030, with 2015 as baseline. We aimed to describe the European Union/European Economic Area (EU/EEA) baseline mortality from liver diseases, as defined by WHO Core-10 indicator through ICD-10 codes, and estimate mortality attributable to HBV and HCV.Methods: Age-standardised mortality rates per 100,000 for hepatocellular carcinoma (HCC, ICD-10 C22.0), chronic liver disease (CLD, ICD-10 K72-K75) and chronic viral hepatitis B and C (CHB/CHC, ICD-10 B18.1-B18.3) were calculated by gender, age-group and country using 2015 Eurostat data. Because aetiology fraction (AF) estimates were lacking for HCC and CLD as defined by C10, number of deaths in EU/EEA countries in 2015 from liver cancer (ICD-10 C22) and 'cirrhosis and other chronic liver diseases' (ICD-10 B18-B18.9, I85-I85.9, I98.2, K70-K70.3, K71.7, K74-K74.9, K75.2, K75.4-K76.2, K76.4-K76.9 and K77.8) were adjusted by corresponding AF estimates from Global Burden of Disease publications.Results: In 2015, there were wide variations across countries in mortality rates from HCC, CLD and CHB/CHC. A 2015 mortality baseline of 63,927 deaths attributable to HBV and HCV is proposed, that includes 55% of liver cancer and 45% of 'cirrhosis and other chronic liver diseases' deaths.Conclusions: The HBV and HCV attributable mortality in the EU/EEA is high. Greater efforts are needed to identify HBV and HCV infections at an early stage and link cases to care to reduce mortality from liver diseases. Country-specific AF estimates are needed to accurately estimate HBV, HCV associated mortality.

High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder.

Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.

Primary cultures of aspiration residual specimens predict outcomes of hepatocellular carcinoma patients receiving curative treatment.

The utility of primary culture originated from the residual aspiration specimens to predict outcomes of hepatocellular carcinoma patients receiving curative treatment was investigated. A total of 105 American Joint Committee on Cancer TNM stage I or II patients were included. The culture results were determined at the 28th of culture and were divided into rapid proliferation of cancer cells alone, rapid proliferation of both cancer cells and cancer-associated fibroblasts, rapid proliferation of cancer-associated fibroblasts alone, slow proliferation, and no outgrowth of plating specimens. Our results showed that outgrowths of cultured cells from plated particles were achieved in 98.1% of patients. Sixty-nine patients (65.7%) showed rapid proliferation of cultured cells (11 rapid proliferation of cancer cells alone, 17 rapid proliferation of both cancer cells and cancer-associated fibroblasts, and 41 rapid proliferation of cancer-associated fibroblasts alone). There was no significant difference in the incidence of recurrence or survival between patients with normal and abnormal serum alpha-fetoprotein levels, chronic hepatitis B and chronic hepatitis C, TNM stage I and stage II, histological high-grade and low-grade hepatocellular carcinoma, and between patients treated by operative resection and local abrasion. Only patients with rapid proliferation of cancer cells ± rapid proliferation of cancer-associated fibroblasts showed significantly higher incidence of recurrence than patients with other growth types (P = .0482), but there was no significant difference in survival between two groups. In conclusion, primary culture using this method is clinically feasible and can be applied to predict recurrence of hepatocellular carcinoma patients receiving curative treatment.

Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study.

BACKGROUND & AIMS: Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS: We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR). RESULTS: Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality. CONCLUSIONS: Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies. LAY SUMMARY: Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.

A hallmark for the development and progression of chronic liver diseases is the persistent dysregulation of signaling pathways related to inflammatory responses, which eventually promotes the development of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The two major etiological agents associated with these complications in immunocompetent patients are hepatitis B virus (HBV) and hepatitis C virus (HCV), accounting for almost 1.4 million liver disease-associated deaths worldwide. Although both differ significantly from the point of their genomes and viral life cycles, they exert not only individual but also common strategies to divert innate antiviral defenses. Multiple virus-modulated pathways implicated in stress and inflammation illustrate how chronic viral hepatitis persistently tweaks host signaling processes with important consequences for liver pathogenesis. The following review aims to summarize the molecular events implicated in the sensing of viral nucleic acids, the mechanisms employed by HBV and HCV to counter these measures and how the dysregulation of these cellular pathways drives the development of chronic liver disease and the progression toward HCC.

Elevated Fatty Liver Index as a Risk Factor for All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis C Virus-Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study).

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality. APPROACH AND RESULTS: After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17-3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], P = 0.004), advanced fibrosis (1.77 [1.00-3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], P < 10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74-4.79], P < 10-3 ). CONCLUSIONS: An elevated FLI (≥60) is a risk factor for all-cause mortality in HIV-HCV-coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.

Hepatitis C Virus Epidemiology and the Impact of Interferon-Free Hepatitis C Virus Therapy.

The public health impact of hepatitis C virus (HCV) infection has been realized only recently. Globally, 71 million people are living with HCV chronic infection. HCV prevalence is higher in some regions and countries, as well as in some subpopulations such as people who inject drugs, prisoners, or people living with HIV. In 2017, an estimated 580,000 people died from HCV, largely because of long-term complications of the disease. The advent of direct-acting antivirals (DAAs), which are highly effective in treating the infection and are well tolerated, led the World Health Organization (WHO) in 2016 to call for the elimination of HCV by 2030, which would be possible by meeting the numerical targets laid down by the organization. However, at present, only 12 countries are on track. Overall, only 20% of people with HCV have been diagnosed and only 7% of people diagnosed have initiated treatment, with major differences among countries. Underdiagnoses, a general lack of awareness, poor surveillance, and the prices of diagnostics and treatment remain major barriers to achieving the elimination goals. Comprehensive strategies, which include innovative models of care and the removal of reimbursement restrictions for treatment, are needed to overcome these public health and health system obstacles.

Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short- and long-term IFN-free antiviral treatment.

Background: New direct-acting antiviral drugs can eradicate hepatitis C virus (HCV) infection in over 90% of patients and can even reduce the risk of complications in advanced fibrosis/cirrhosis. The aims of this study were to evaluate (1) changes in fibrosis during and after antiviral treatment and (2) incidence of hepatocarcinoma and mortality in various fibrosis stages.Methods: This is a longitudinal monocentric prospective study. Blood and instrumental examinations were evaluated at baseline, at the end of therapy, and 1 and 2 years following treatment.Results: Two hundred and ninety-six patients with chronic HCV were evaluated, of whom 115 were experienced, 181 were treatment-naïve, and 2 had previous hepatocellular carcinoma (HCC) and were therefore excluded from the study. At baseline, stiffness values were 13.46 ± 9.97 kPa. Out of the 294 HCV patients enrolled, 100 had lymphoproliferative disorders and were evaluated separately. This group of patients showed stiffness values pertaining to the F0-F2 group (mean stiffness values were 6.07 ± 1.68 kPa). All other patients showed stiffness values pertaining to the F3-F4 group (mean stiffness values were 17.93 ± 10.23). No statistically significant difference was found between stiffness at baseline compared to the end of treatment (EOT), while significant differences were found between the baseline, 1 year (p = .05), and 2 year follow-ups (p < .01). Significant differences were found between baseline and EOT, as well as 1 and 2 years after the end of treatment (p < .001) in the F3-F4 group. Four out of 140 patients with baseline cirrhosis developed HCC during the post-treatment follow-up, 1 of whom died.Conclusions: Non-invasive methods provide important prognostic information, particularly concerning the observed regression of fibrosis and could be extremely useful for monitoring patients with long life expectancies after direct-acting antiviral treatment.

Análisis coste-efectividad del tratamiento de la hepatitis C crónica en población reclusa en España / Cost-effectiveness analysis of chronic hepatitis C treatment in the prison population in Spain

OBJETIVOS: Evaluar, en presos con hepatitis C crónica (HCc) pendientes de tratamiento, el coste-efectividad de tratarlos con antivirales de acción directa (AAD) frente a no tratarlos, y analizar el impacto clínico y económico del tratamiento sobre las complicaciones hepáticas y la mortalidad. MATERIAL Y MÉTODO: Se desarrolló un modelo de Markov para simular el tratamiento y proyectar la progresión de la enfermedad de una cohorte estimada de 4.408 reclusos con HCc tratados con AAD en dos años (el 50% cada año) frente a ningún tratamiento. En los tratados, se asoció una respuesta viral sostenida del 95%. Las características de los pacientes, las probabilidades de transición, las utilidades y los costes (farmacológicos y estados de salud) se obtuvieron de publicaciones científicas. El modelo estimó costes y resultados en salud, la relación coste-utilidad incremental (RCUI), a partir de los costes totales y años de vida ajustados por calidad (AVAC) y los eventos clínicos evitados. La perspectiva fue la del Sistema Nacional de Salud (SNS) y se aplicó una tasa de descuento anual (el 3%) para costes y resultados en salud. La robustez de los resultados se evaluó mediante un análisis de sensibilidad. RESULTADOS: En la población tratada, el modelo estimó una reducción del 92% de los casos de cirrosis descompensada y del 83% de carcinoma hepatocelular, se evitaron 132 trasplantes hepáticos y disminuyó el 88% la mortalidad hepática. El tratamiento consiguió 5,0/AVAC adicionales (21,2 frente al 16,2), con un coste incremental de 3.473 euros (24.088 € frente a 20.615 €) por paciente y una RCUI de 690 €/AVAC ganado. DISCUSIÓN: Considerando el umbral de disponibilidad a pagar utilizado en España (22.000-30.000 €/AVAC), el tratamiento con AAD en los presos con HCc es una estrategia altamente coste-efectiva, reduce la transmisión, aumenta la supervivencia y reduce las complicaciones hepáticas, así como los costes asociado a su manejo

OBJECTIVES: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. MATERIAL AND METHOD: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. RESULTS: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. DISCUSSION: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma.

With the increasing use of direct-acting antivirals (DAA) for treatment of chronic hepatitis C virus (HCV) infection, we looked at the impact of DAA use and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and HCV. This is a retrospective analysis of 969 HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Median overall survival of the cohort was 24.2 months. 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (67.4%). HCV-positive and HCV-negative patients had similar survival, 20.7 months vs 17.4 months (p = 0.22). Patients receiving DAA therapy had an overall survival of 71.8 months vs 11.6 months for patients without (p < 0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months vs. 26.7 months in the non SVR12 group (p < 0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location, cancer treatment type, receiving DAA treatment and achieving SVR12 had independent influence on survival (p < 0.05). This suggests DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.

Monitoring liver transplant rates in persons diagnosed with hepatitis C: a data linkage study, England 2008 to 2017.

IntroductionLiver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease.AimsTo describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage.MethodsThis is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates.ResultsOf 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3-6.8 years). Liver transplant rates were lower 2014-17 compared with 2011-13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55-0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry.ConclusionIn the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.

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.

Acute cellular rejection in hepatitis C recipients following liver transplantation in the era of direct-acting antivirals: chronological analysis of the United Network for Organ Sharing database.

INTRODUCTION: Interferon (IFN) treatment for liver transplant (LT) recipients with hepatitis C virus (HCV) increases acute cellular rejection (ACR) and worsens graft and patient survival. It is unknown if direct-acting antivirals (DAAs) affect rejection rates or post-transplant survival. METHOD: The United Network for Organ Sharing STAR files of December 2017 (n = 25,916) were analyzed. RESULTS: Compared with non-HCV-LT, HCV-LT survival was worse in the IFN-era (2007-2008) and IFN+DAA-era (2011), but not in the DAA-era (2014-2015). ACR6m rate has been less frequent in newer eras and was lower in HCV-LT than in non-HCV-LT in both the DAA-era (6.9% vs. 9.3%, P < 0.001) and in the IFN+DAA-era (8.8% vs. 11.8%, P = 0.001), but not in the IFN-era (10.8% vs. 11.0%, P = 0.39). HCV-LT recipients who had ACR6m had worse 2-year survival than those without ACR6m, in the IFN-era (80.0% vs. 88.4%, P < 0.0001) and in the IFN+DAA-era (81.4% vs. 89.2%, P < 0.01) but not in the DAA-era (90.4% vs. 93.2%, P = 0.085). Cox proportional hazard model identified ACR6m as independent risk factor for mortality in HCV-LT in the IFN-era (HR = 1.88, P ≤ 0.001) and in the IFN+DAA-era (HR = 1.84, P = 0.005), but not in the DAA-era (P = n.s.). CONCLUSIONS: Two-year survival of HCV-LT recipients were significantly better in the DAA-era; these were associated with reduced rate and impact of ACR6m.