Timely Albumin Infusion May Improve Resource Utilization in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis.

Spontaneous bacterial peritonitis is a life-threatening complication of cirrhosis that can increase healthcare utilization. The impact of albumin administration timing on hospital resource utilization and its optimal timing is unclear, despite its efficacy in improving survival for cirrhosis patients with spontaneous bacterial peritonitis. A retrospective study was conducted to evaluate the influence of the timing of albumin administration on the length of stay and total hospital cost for patients with cirrhosis and spontaneous bacterial peritonitis who require fluid resuscitation. The study utilized de-identified data from Cerner Health Facts® data. Adult inpatients with a diagnosis of cirrhosis and SBP receiving ≥1 antibiotic and fluid resuscitation between January 1, 2009, and April 30, 2018, were included and stratified by albumin administration timing: ≤24 hours from hospital admission ("timely albumin") or >24 hours of admission or no albumin ("non-timely albumin"). We used a Kaplan-Meier curve with log-rank test to evaluate the association between timing of albumin administration and time to hospital discharge and a generalized linear model to examine the association between albumin timing and total hospital costs. We identified 1,308 hospitalizations, of which 301 contained valid cost data. The timely albumin group had a median time to discharge of 6.95 days compared to 7.78 days in the non-timely group (p = 0.02). Cost model showed that receiving timely albumin incurred 16% lower costs (p = 0.027) than patients in the non-timely albumin group. Timely albumin administration with an antibiotic regimen may shorten the length of stay and lower costs, thereby reducing hospital resource utilization in patients with cirrhosis and spontaneous bacterial peritonitis requiring fluid resuscitation.

Cost-effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece.

Aim: This study assessed the clinical impact and cost-effectiveness of switching from tenofovir disoproxil fumarate (TDF) to either tenofovir alafenamide (TAF) or entecavir (ETV) in a Greek chronic hepatitis B (CHB) population. Patients & methods: A Markov model from the perspective of a third-party payer in Greece quantified the health and economic benefits of switching from TDF to either TAF or ETV over a lifetime horizon. Results: Over a lifetime, patients who switch from TDF to TAF versus patients who switch from TDF to ETV had an overall lower incidence of compensated cirrhosis (0.4% lower), decompensated cirrhosis (0.04% lower) and hepatocellular carcinoma (0.25% lower). Chronic kidney disease and end-stage renal disease were also lower in patients who switch to TAF; major osteoporotic fractures were similar for both groups. While total costs were higher for switching from TDF to TAF versus TDF to ETV due to the higher cost of TAF, switching from TDF to TAF versus ETV was cost effective with an incremental cost-effectiveness ratio of €17,113 per quality-adjusted life year. Conclusion: Switching from TDF to TAF in patients living with CHB is a cost effective strategy to reduce adverse liver disease outcomes, while improving bone- and renal-related safety outcomes.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

BACKGROUND: Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. METHODS: A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. RESULTS: Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. CONCLUSIONS: This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. METHODS AND FINDINGS: We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. DISCUSSION: PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

[Assessment of body mass index in patients with chronic hepatitis C who received an effective antiviral therapy].

AIM: To evaluate the body mass index (BMI) in patients with chronic hepatitis C (CHC) with different stages of liver fibrosis and steatosis who received effective antiviral therapy (AVT). MATERIALS AND METHODS: The study included 278 CHC patients with a sustained virologic response (SVR) at the end of treatment. In addition to assessing the investigational data to determine the clinical status of the patient, we calculated BMI (following the World Health Organization guidelines) and determined the severity of liver fibrosis (F) and steatosis (S) using transient elastography. The patients were assessed at the start of antiviral therapy, after ≥6 months from the moment SVR was confirmed, and then every 12 to 24 months. RESULTS: By the end of the study, the mean patient age was 49 years, 53% of them were men, and 34% of the patients were obese. Excessive weight gain was registered in 17% (n=48) of the cases, with 60% newly diagnosed with Class 1 to 2 obesity. Both before the start of AVT and years after reaching SVR, the mean BMI corresponded to the reference pre-obesity values, the liver steatosis was significantly more often absent in normal BMI; on the contrary, fatty liver (predominantly S2 to S3) was registered in individuals with elevated BMI (p<0.0001). After the long-term period following a successful therapy, Stage F4 liver fibrosis patients were mainly diagnosed with obesity (80% versus 44% before AVT; p=0.0010). CONCLUSION: The high proportion of patients with elevated BMI and liver steatosis seen years after a successful CHC therapy indicates a continued risk of progression of chronic liver disease. Such patients should be advised on how important it is to change their lifestyle to reduce overweight and prevent weight gain. We also need long-term assessments of how liver steatosis changes over time and what are the outcomes associated with post-SVR increase in BMI.

Assessment of liver fibrosis in patients with rheumatoid arthritis treated with methotrexate: Utility of fibroscan and biochemical markers in routine clinical practice.

OBJECTIVES: To study the prevalence of liver fibrosis (LF) measured by FibroScan and APRI index in patients with rheumatoid arthritis (AR) undergoing treatment with methotrexate (MTX). METHODS: We included 59 patients with RA on MTX. Medical records, FibroScan measures and serological markers of liver damage were compared on the basis of cumulative methotrexate dose. RESULTS: Mean treatment duration was 82.4±65.1 months and mean cumulative dose was 5214.5±4031.9mg. Five patients met LF criteria by fibroscan, while only one patient had a suggestive APRI score. No statistically significant differences were found in terms of LF measured by both APRI and fibroScan between patients with cumulative doses above and below 4000mg. There was also no relationship between LF and treatment duration. CONCLUSIONS: The occurrence of LF in patients with RA on MTX is a multifactorial process that does not seem directly related to its cumulative dose. FibroScan may be a useful technique in clinical practice to screen for this complication.

Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C.

OBJECTIVE: The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). SUBJECTS: This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. METHODS: Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. RESULTS: Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). CONCLUSIONS: Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.

Low-Cost Predictors for Liver Function and Clinical Outcomes after Sustained Virological Response in Patients with HCV-Related Cirrhosis and Thrombocytopenia.

Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the benefits of treating hepatitis C virus cirrhotic patients, but there is still some need for clarification concerning the real impact on the long-term evolution after achieving sustained virological response; there is no general consensus in the literature about identifying the patients that do not improve post-treatment. Materials and Methods: Our retrospective analysis investigated the long-term (2 years) evolution of 46 patients with cirrhosis with thrombocytopenia, previously infected with VHC, treated and who obtained an SVR after DAA treatment. Results: Despite the overall improvement, 8.7% patients developed hepatocellular carcinoma and 6.5% patients ascites/upper GI bleeding. We found that FIB-4, MELD and AFP changes at 1 year were the most significant predictors for these outcomes. Additionally, a drop in leukocyte count after 1 year seemed to indicate a risk for hepatocellular carcinoma, but this was not consistent. Conclusions: It might be beneficial to intensify the surveillance for post-treatment adverse liver effects for the patients with these marker changes at 1 year.

Glycomics-based serum markers as reliable tool for assessment of viral response after treatment with direct-acting antiviral drugs in hepatitis C virus infection.

OBJECTIVES: Patients with chronic hepatitis C virus (HCV) infection have a genuine risk of developing liver fibrosis and cirrhosis, potentially resulting in hepatocellular carcinoma (HCC), a risk that remains even after sustained viral response (SVR). Glycomics-based biomarkers are an attractive tool to closely monitor these patients during and after antiviral treatment, as alterations in the abundance of N-glycans reflect an altered state of the liver. This study assessed serum glycomics for the evaluation of inflammation-related fibrosis regression during and after treatment of HCV with DAAs. METHODS: The GlycoFibroTest and GlycoCirrhoTest were analyzed in the sera 36 HCV-infected patients with advanced fibrosis (F3) or established cirrhosis (F4), before (week 0), during (week 12) and after (week 24) a twelve-week oral administration of DAAs therapy - using an optimized glycomic technology on a DNA sequencer. RESULTS: All patients achieved SVR after treatment and two of them developed HCC in the subsequent five years. A significant decrease of the GlycoFibroTest (p < 0.0001) was seen after 12 weeks, consistent with other measured biomarkers (APRI, FIB-4, FibroTest). Statistical analysis was performed in IBM SPSS Statistics version 28.0, using the non-parametric Friedman's test with a statistical significance α level of 0.05. CONCLUSION: This study suggests that the GlycoFibroTest is a serum biomarker for viral response in HCV patients. The rapid decrease of the glycomics-based biomarker probably reflects the amelioration of liver inflammation as underlying process, rather than the improvement of liver fibrosis itself.

Assessment of factors affecting response of direct-acting antivirals in chronic hepatitis C patients.

Background: Hepatitis C virus (HCV) is a universally prevalent pathogen and a major cause of liver-related morbidity and mortality worldwide. The evolution of antiviral therapy for HCV has rapidly progressed from interferon (IFN)-based therapies to IFN-free combinations of direct-acting antivirals (DAAs). Aims: This study aims to assess the response of DAAs in chronic hepatitis C (CHC) patients and to study the various factors affecting the response of DAAs in CHC. Settings and Design: This longitudinal observational study spanning over a year was conducted in the Medicine department of a tertiary care teaching hospital. Materials and Methods: The study was conducted on 400 adult CHC patients, diagnosed by a positive anti-HCV antibody test and a detectable viral load (HCV RNA) by real time polymerase chain reaction (RT-PCR), registered for treatment with DAAs. The first 400 patients satisfying the eligibility criteria were enrolled by non-probability consecutive sampling. All the participants were treated as per the National Viral Hepatitis Control Programme (NVHCP) guidelines. Repeat HCV viral load was done at or after 12 weeks of completion of anti-viral therapy to ascertain sustained virological response (SVR). Various factors which might predict treatment response were analyzed. Statistical Analysis Used: The continuous variables were expressed as mean and standard deviation, while the categorical variables were summarized as frequencies and percentages. The Student's independent t-test was employed for the comparison of continuous variables. The Chi-square or Fisher's exact test, whichever is appropriate, was employed for the comparison of categorical variables. Multivariate Logistic Regression was used to identify the independent predictors of treatment nonresponse. A P < 0.05 was considered statistically significant. Results: The mean age of the subjects was 42.3 ± 15.23 years with a male-to-female ratio of 1.96:1. Most of the patients (80.5%) were non-cirrhotic; among 19.5% cirrhotic, 13% were compensated while 6.5% were decompensated cirrhotic. The overall SVR done at or after 12 weeks of completion of treatment was 88.75%. Age, gender distribution, occupation, socioeconomic status, educational status, body mass index, treatment regimen, duration of treatment, and baseline viral load did not alter the treatment response. Among comorbidities, only diabetes mellitus (DM) and human immunodeficiency virus (HIV) co-infection adversely affected the treatment response (P = 0.009 and P < 0.001, respectively). Intravenous (IV) drug abuse was significantly associated with treatment failure (P < 0.001). The presence of liver cirrhosis (P < 0.001), thrombocytopenia (P < 0.001), elevated transaminases (alanine transaminase: P = 0.021, aspartate transaminase: P < 0.001), and previous treatment experience (P = 0.038) were other significant predictors of treatment failure. Conclusions: DAAs are highly efficacious drugs in the treatment of CHC with a high rate of treatment response. Significant predictors of CHC treatment failure included comorbidities especially DM and HIV co-infection, IV drug abuse, presence of liver cirrhosis, thrombocytopenia, elevated transaminases, and previous treatment experience. However, independent predictors of treatment nonresponse observed in this study were thrombocytopenia, IV drug abuse, and liver cirrhosis.

Résumé Contexte: Le virus de l'hépatite C (VHC) est un agent pathogène universellement répandu et une cause majeure de morbidité et de mortalité liées au foie dans le monde. L'évolution de la thérapie antivirale pour le VHC a rapidement progressé des thérapies à base d'interféron (IFN) à des combinaisons sans IFN de médicaments à action directe antiviraux (AAD). Objectifs: Cette étude vise à évaluer la réponse des AAD chez les patients atteints d'hépatite C chronique (HCC) et à étudier les différents facteurs affectant la réponse des AAD dans les CHC. Cadres et conception : Cette étude observationnelle longitudinale s'étalant sur un an a été menée dans le département de médecine d'un hôpital universitaire de soins tertiaires. Matériels et méthodes: L'étude a été menée sur 400 patients adultes atteints d'HCC, diagnostiqués par un test d'anticorps anti-VHC positif et une charge virale détectable (ARN du VHC) par réaction en chaîne par polymérase en temps réel, inscrit pour le traitement par DAA. Les 400 premiers patients répondant aux critères d'éligibilité ont été enrôlés par échantillonnage consécutif non probabiliste. Tous les participants étaient traités conformément aux directives du programme national de contrôle de l'hépatite virale. La charge virale répétée du VHC a été effectuée à ou après 12 semaines d'achèvement traitement antiviral pour déterminer la réponse virologique soutenue (RVS). Divers facteurs susceptibles de prédire la réponse au traitement ont été analysés. Analyse statistique utilisée: les variables continues ont été exprimées sous forme de moyenne et d'écart-type, tandis que les variables catégorielles ont été résumés sous forme de fréquences et de pourcentages. Le test t indépendant de Student a été utilisé pour la comparaison des variables continues. Le chi carré ou Le test exact de Fisher, selon le cas, a été utilisé pour la comparaison des variables catégorielles. La régression logistique multivariée a été utilisée identifier les prédicteurs indépendants de la non-réponse au traitement. A P < 0.05 était considéré comme statistiquement significatif. Résultats: L'âge moyen des sujets était de 42.3 ± 15.23 ans avec un ratio hommes-femmes de 1.96:1. La plupart des patients (80.5%) étaient non cirrhotiques ; parmi 19.5% de cirrhose, 13% étaient compensés alors que 6.5% étaient cirrhotiques décompensés. La RVS globale effectuée à 12 semaines ou après la fin du traitement était 88.75%. Âge, répartition par sexe, profession, statut socio-économique, niveau d'instruction, indice de masse corporelle, schéma thérapeutique, durée du traitement, et la charge virale de base n'a pas modifié la réponse au traitement. Parmi les comorbidités, seuls le diabète sucré (DM) et l'immunodéficience humaine la co-infection par le virus (VIH) a affecté négativement la réponse au traitement (P = 0.009 et P < 0.001, respectivement). L'abus de drogues par voie intraveineuse (IV) a été significativement associée à l'échec du traitement (P < 0.001). La présence de cirrhose du foie (P < 0.001), thrombocytopénie (P < 0.001), élévation les transaminases (alanine transaminase: P = 0.021, aspartate aminotransférase: P < 0.001) et l'expérience de traitement antérieure (P = 0.038) étaient d'autres facteurs prédictifs significatifs d'échec thérapeutique. Conclusions: les AAD sont des médicaments très efficaces dans le traitement de l'HCC avec un taux de traitement élevé réponse. Les facteurs prédictifs significatifs d'échec du traitement des CHC comprenaient les comorbidités, en particulier la co-infection par le diabète et le VIH, l'abus de drogues par voie intraveineuse, la presence de cirrhose du foie, de thrombocytopénie, d'élévation des transaminases et d'antécédents de traitement. Cependant, des prédicteurs indépendants du traitement les non-réponses observées dans cette étude étaient la thrombocytopénie, l'abus de drogues intraveineuses et la cirrhose du foie. Mots-clés: Cirrhose, antiviraux à action directe, virus de l'hépatite C, toxicomanie par voie intraveineuse, réponse virologique soutenue, thrombocytopénie.

Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study.

INTRODUCTION: Low-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting. METHODS: A Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%. RESULTS: Among people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL. CONCLUSION: Initiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.

Incidence of, Risk Factors for, and Outcomes After Ascites in a Population-Based Cohort of Older Americans.

BACKGROUND: The incidence of, risk factors for, and outcomes after the development of ascites are poorly described for contemporary patients with cirrhosis. METHODS: We examined data for a 20% random sample of US Medicare enrollees with cirrhosis and Part D prescription coverage from 2008 to 2019, excluding patients with heart failure and diuretic use prior to cirrhosis. Among 63,364 persons with cirrhosis, we evaluated the incidence of ascites using an Aalen-Johansen estimator. We evaluated risk factors for ascites, mortality, and mortality after ascites using multistate modeling. We determined the associations with each outcome for an array of medication exposures including nonselective beta-blockers, antiviral therapy, statins, rifaximin, anticoagulants, and metformin. RESULTS: The cumulative incidence of ascites was 5.1%, 9.5%, and 10.7% and 1, 3, and 5 years overall. The corresponding data for ascites requiring paracentesis were 1%, 2.1%, and 2.4%. Persons aged < 65 years, with alcohol-related cirrhosis, varices, or HE, are most likely to develop ascites. The risk of ascites was higher for persons taking any NSBB (including carvedilol) but lower for those taking atorvastatin (but not other statins) and antiviral therapy for Hepatitis C. Incident ascites was associated with increased risk of death, HR 27.6 95%CI(21.7-35.1). Survival following ascites was 1.08 years (interquartile range, IQR, 0.26-2.75), 0.38 years (IQR0.1-1.3) for those requiring paracentesis. Lipophilic statins were the only medications associated with lower mortality after ascites requiring paracentesis. CONCLUSIONS: Ascites is associated with a high risk of death. Very few candidate therapies are associated with the reduction in the risk of ascites and mortality after ascites development.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Tigecycline population pharmacokinetics in critically ill patients with decompensated cirrhosis and severe infections.

OBJECTIVES: Physiopathological changes in advanced cirrhosis could alter tigecycline pharmacokinetics (PK), thus affecting serum drug concentrations and compromising target attainment. We aimed to describe tigecycline PK in patients with decompensated cirrhosis and severe bacterial infections, identify the sources of PK variability and assess the performance of different dosing regimens to optimize the PK/pharmacodynamic (PD) target. METHODS: Serum concentrations and covariates were obtained from patients with severe infections under tigecycline treatment. A population PK analysis was performed using non-linear mixed-effects modelling and the final model was used to simulate tigecycline exposure to assess the PTA. RESULTS: Twenty critically ill patients were enrolled in the study. Data were best described by a two-compartment linear model. Mean ± SD parameter estimates for clearance (CL), intercompartmental clearance (Q), central and peripheral volumes of distribution (V1 and V2) were 14.8 ± 11 L/h, 38.4 ± 24 L/h, 63.7 ± 14 L and 233 ± 30 L, respectively. MELD score significantly influenced tigecycline CL, and total serum proteins significantly affected V1. Monte Carlo simulations showed that tigecycline elimination is hampered as MELD score values increase, consequently requiring lower drug doses. Patients with hypoproteinaemia would have lower peak tigecycline concentrations but similar steady-state concentrations compared with patients with normoproteinaemia. CONCLUSIONS: Our study confirms that tigecycline dose adjustment is needed in severe hepatic dysfunction and suggests using the MELD score for dose optimization since it is identified as a covariate that significantly influences tigecycline CL. Dosing regimens are recommended to reach several PK/PD targets considering this clinical variable and any MIC within the susceptibility range.

Assessment of the Biological Activities of Egyptian Purslane (Portulaca oleracea) Extract after Incorporating Metal Nanoparticles, in Vitro and in Vivo Study.

OBJECTIVE: Egyptian Purslane (Portulaca oleracea) is rich in omega-3 fatty acids and a wide range of vitamins and phyto-constituents that were absorbed slowly due to their high molecular weights. Therefore, this study was designed to accelerate the absorption of these phyto-constituents and hence increase their bioavailability by incorporating silver (Ag-NPs) and zinc oxide nanoparticles (ZnO-NPs) due to their impressive properties. METHODS: The major phyto-constituents and different biological activities were quantified in aqueous extract before and after incorporating metal nanoparticles (M-NPs). The efficiency of ZnO-P. nano-extract was studied on cell cycle and apoptosis of human hepatocellular carcinoma (HEPG-2) cells. Then, both Ag- and ZnO-P. nano-extracts were studied against hepatic fibrosis induced by thioacetamide (TAA) in rats through undergoing different hematological and biochemical measurements in addition to the histopathological examination in hepatic tissues compared to the extract itself. RESULTS: The ZnO-P. nano-extract showed significantly (P<0.05) higher antioxidant and scavenging activity due to the existence of higher total polyphenolic content. Also, it exhibited a significantly (P<0.05) higher inhibitory effect on acetyl cholinesterase (AChE) activity and higher cytotoxic activity against HEPG-2 cells. Therefore, ZnO-P. nano-extract was studied against the cell cycle and apoptosis of HEPG-2 cells compared to the extract itself. It was found that ZnO-P. nano-extract was safer than Ag-P. nano-extract. Both Ag- and ZnO- P. nano-extracts were studied against the hepatic fibrosis induced by thioacetamide (TAA) compared to the native extract. It was noticed that ZnO-P. nano-extract exhibited an ameliorative effect against hepatic fibrosis by decreasing levels of inflammatory and fibrotic markers significantly (P<0.05) more than Ag-P. nano-extract. Furthermore, it improved the antioxidant status of the hepatic tissue in addition to restoring the histopathological architecture of liver tissue. CONCLUSION: ZnO-P. nano-extract showed higher in vitro and in vivo biological activities than Ag-P. nano-extract and native P. extract itself.

Eficacia y seguridad de sofosbuvir / velpatasvir en pacientes adultos postrasplante de medula ósea con infección crónica por el virus de la hepatitis C, con grado de fibrosis hepática F0 y sin tratamiento previo / Efficacy and safety of sofosbuvir/velpatasvir in adult post-bone marrow transplant patients with chronic hepatitis C virus infection, with liver fibrosis grade F0 and without prior treatment

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de sofosbuvir/velpatasvir (SOF/VEL) en pacientes adultos postrasplante de medula ósea con infección crónica por el virus de la hepatitis C (VHC), con grado de fibrosis hepática FO y sin tratamiento previo. Así, la Dra. Estefanía Liza Baca especialista en Gastroenterología del Hospital Nacional Edgardo Rebagliati Martins, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso fuera del petitorio del producto SOFNEL. ASPECTOS GENERALES: La infección crónica por el virus de la hepatitis C (VHC) sigue siendo un problema de salud pública, a nivel mundial, con 71 millones de personas viviendo con el VHC. De ellos, aproximadamente, de 290 000 a 399 000 pacientes por año fallecen por complicaciones asociadas, incluyendo cirrosis hepática, carcinoma hepatocelular y falla hepática (OMS 2021; 2017). En el Perú, la prevalencia de infección crónica por el VHC no se conoce con exactitud; sin embargo, de acuerdo a algunos estudios seroepidemiológicos realizados en el país, se ha estimado entre 0.25 % a 1 % aproximadamente, con una tasa de mortalidad por el VHC de 0.04 por 100 000 habitantes (Colichon Yerosh et al. 2004; Dávalos Moscol 2009; Farfán y Cabezas 2003; Sanchez et al. 2000). Algunos pacientes con infección crónica por el VHC presentan comorbilidades u otras condiciones (i.e. trasplante de células madre) que pueden acelerar la progresión de la enfermedad a problemas hepáticos graves como: cirrosis, cáncer hepático y necesidad de trasplante hepático. El objetivo de la terapia antiviral en pacientes con infección crónica por el VHC es disminuir el ARN del VHC a niveles indetectables (AASLD 2021; EASL 2020), definido mediante el logro de una respuesta viral sostenida a las 12 semanas después del tratamiento (RVS12) (Chopra 2020). La ribavirina y el interferón pegilado han sido tradicionalmente los \ tratamientos para la infección crónica por el VHC; sin embargo, en los últimos años, el """" " " I desarrollo de los agentes antivirales de acción directa (AAD) y AAD pangenotípicos han ido 1 desplazando su uso, debido a mejores tasas de RVS (e.g. SOFNEL) con mejores perfiles de seguridade. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad de SOFNEL en pacientes adultos postrasplante de medula ósea con infección crónica por el VHC, con grado de fibrosis hepática FO y sin tratamiento previo. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), el Scottish Intercollegiate Guidelines Network (SIGN), el Institute for Quality and Efficiency in Healthcare (IQWiG por sus siglas en alemán), la International Database of GRADE Guideline, el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Guidelines International Network (GIN), National Health and Medical Research Council (NHMRC), la Cancer Guidelines Database, el New Zealand Guidelines Group (NZGG), el Instituto de Evaluación Tecnológica en Salud (IETS), el Instituto de Efectividad Clínica y Sanitaria (IECS), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la OMS, el Ministerio de Salud del Perú (MINSA) y el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en estudios del hígado, infectología y trasplante de medula ósea, tales como: la American Association for the Study of Liver Disease (AASLD), la European Association for the Study of the Liver (EASL), la Infectious Diseases Society of America (IDSA), American Society for Blood and Marrow Transplantation, Finalmente, se realizó una búsqueda en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica hasta diciembre de 2021, se identificó una GPC elaborada por la European Association for the Study of the Liver en el 2020 (EASL 2020). No se identificaron ETS, ECA o RS de ECA o estudios observacionales comparativos que respondieran a la pregunta PICO de interés del presente dictamen. En tal sentido se optó por incluir el ECA que sirvió de base para la aprobación de SOFNEL ante la Food and Drug Administration y la European Medicine Agency. Así, se incluyó al ECA ASTRAL-1 publicado por Feld et al. en el 2015. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de SOFNEL para pacientes adultos postrasplante de medula ósea con infección crónica por el VHC, con grado de fibrosis hepática FO y sin tratamiento previo, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Emerging Role of Interleukins for the Assessment and Treatment of Liver Diseases.

BACKGROUND: The most common liver diseases are fibrosis, alcoholic liver disease, nonalcoholic fatty disease, viral hepatitis, and hepatocellular carcinoma. These liver diseases account for approximately 2 million deaths per year worldwide, with cirrhosis accounting for 2.1% of the worldwide burden. The most widely used liver function tests for diagnosis are alanine transaminase, aspartate transaminase, serum proteins, serum albumin, and serum globulins, whereas antivirals and corticosteroids have been proven to be useful for the treatment of liver diseases. A major disadvantage of these diagnostic measures is the lack of specificity to a particular tissue or cell type, as these enzymes are common to one or more tissues. The major adverse effect of current treatment methods is drug resistance. To overcome these issues, interleukins have been investigated. The balance of these interleukins determines the outcome of an immune response. Interleukins are considered interesting therapeutic targets for the treatment of liver diseases. In this review, we summarize the current state of knowledge regarding interleukins in the diagnosis, treatment, and pathogenesis of different acute and chronic liver diseases. OBJECTIVE: To understand the role of interleukins in the assessment and treatment of different types of liver diseases. METHODS: A literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: Interleukins, Acute Liver Failure, Alcoholic Liver Disease, Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, Hepatocellular Carcinoma, Inflammation, Liver injury, Hepatoprotective effect. Clinical trial data on these interleukins have been searched on Clinicaltrials.gov. RESULTS: Existing literature and preclinical and clinical trial data demonstrate that interleukins play a crucial role in the pathogenesis of liver diseases. CONCLUSION: Our findings indicate that IL-1, IL-6, IL-10, IL-17, IL-22, IL-35, and IL-37 are involved in the progression and control of various liver conditions via the regulation of cell signaling pathways. However, further investigation on the involvement of these interleukins is necessary for their use as a targeted therapy in liver diseases.