Burden of compensated and decompensated cirrhosis: real world data from an Italian population-based cohort study.

OBJECTIVE: To quantify the annual healthcare resource utilization, costs and mortality rate for a large cohort of Italian patients with compensated (CC) and decompensated cirrhosis (DC). PATIENTS AND METHODS: A population-based cohort study was conducted through the data-linkage of mortality for all-cause, hospitalizations and outpatient drugs and service databases of the Campania Region. All adults hospitalized with cirrhosis diagnosis (2007-2015) were grouped in CC and DC (prevalent patients) on January 1, 2016 and followed for 1-year. Incident patients with DC (2015) were also retrieved and followed from discharge date up to 1-year. Negative binomial regression was used to estimate Incidence Rate Ratios (IRRs) for predictors of all-cause hospitalizations. Costs were evaluated from the Italian National Health Service perspective and expressed in euro patient/year. RESULTS: A total of 21,433 prevalent cirrhotic patients (57.1% CC and 42.9% DC) and 1,371 incident patients with DC were identified. During a 1-year, 21.5% of prevalent patients with CC were admitted for acute events, 26.8% of those with DC and 55.4% of incident patients with DC. Ascites (IRR=1.71;95% CI: 1.37-2.14) and hepatic encephalopathy (IRR=1.35; 95% CI: 1.04-1.77) at index admission were strong predictors of hospitalizations in incident DC patients. The 1-year mortality rate was respectively 5.8% and 10.1% for prevalent patients with CC and DC and 35.6% for incident patients with DC. Direct costs amounted to 3,194€ patient/year for the prevalent CC group and 4,001€ patient/year for the DC group and 13,806 € patient/year for incident individuals with DC. CONCLUSIONS: The burden of cirrhosis dramatically differs between CC and DC patients, especially after the first decompensation episode. Ascites and hepatic encephalopathy at index admission were strong predictors of hospitalizations in incident DC patients.

Innovative strategies for reducing the burden of chronic liver disease.

Alcohol consumption is increasing in the UK, bringing an increased incidence of cirrhosis, which in turn can lead to hepatic encephalopathy. This complication of cirrhosis can be devastating for patients and their families, and incurs a large health economic burden to the NHS. Cirrhosis is, of course, preventable. As disease prevention is at the heart of the NHS Long Term Plan, it can be used as the basis of a 10-year plan to avoid the complications of chronic liver disease.

Outcomes of treatment with CHOP and EPOCH in patients with HIV associated NHL in a low resource setting.

BACKGROUND: The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates, treatment response rates and adverse events in patients with HIV associated NHL treated with CHOP and dose adjusted-EPOCH regimens at the Uganda Cancer Institute. METHODS: A retrospective study of patients diagnosed with HIV and lymphoma and treated at the Uganda Cancer Institute from 2016 to 2018 was done. RESULTS: One hundred eight patients treated with CHOP and 12 patients treated with DA-EPOCH were analysed. Patients completing 6 or more cycles of chemotherapy were 51 (47%) in the CHOP group and 8 (67%) in the DA-EPOCH group. One year overall survival (OS) rate in patients treated with CHOP was 54.5% (95% CI, 42.8-64.8) and 80.2% (95% CI, 40.3-94.8) in those treated with DA-EPOCH. Factors associated with favourable survival were BMI 18.5-24.9 kg/m2, (p = 0.03) and completion of 6 or more cycles of chemotherapy, (p < 0.001). The overall response rate was 40% in the CHOP group and 59% in the DA-EPOCH group. Severe adverse events occurred in 19 (18%) patients in the CHOP group and 3 (25%) in the DA-EPOCH group; these were neutropenia (CHOP = 13, 12%; DA-EPOCH = 2, 17%), anaemia (CHOP = 12, 12%; DA-EPOCH = 1, 8%), thrombocytopenia (CHOP = 7, 6%; DA-EPOCH = 0), sepsis (CHOP = 1), treatment related death (DA-EPOCH = 1) and hepatic encephalopathy (CHOP = 1). CONCLUSION: Treatment of HIV associated NHL with curative intent using CHOP and infusional DA-EPOCH is feasible in low resource settings and associated with > 50% 1 year survival.

Cost-Effectiveness of Rifaximin Treatment in Patients with Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis of the liver causing neuropsychiatric abnormalities. Clinical manifestations of overt HE result in increased health care resource utilization and effects on patient quality of life. While lactulose has historically been the mainstay of treatment for acute HE and maintenance of remission, there is an unmet need for additional therapeutic options with a favorable adverse event profile. Compared with lactulose alone, rifaximin has demonstrated proven efficacy in complete reversal of HE and reduction in the incidence of HE recurrence, mortality, and hospitalizations. Evidence suggests the benefit of long-term prophylactic therapy with rifaximin; however, there is a need to assess the economic impact of rifaximin treatment in patients with HE. OBJECTIVE: To assess the incremental cost-effectiveness of rifaximin ± lactulose versus lactulose monotherapy in patients with overt HE. METHODS: A Markov model was developed in Excel with 4 health states (remission, overt HE, liver transplantation, and death) to predict costs and outcomes of patients with HE after initiation of maintenance therapy with rifaximin ± lactulose to avoid recurrent HE episodes. Cost-effectiveness of rifaximin was evaluated through estimation of incremental cost per quality-adjusted life-year (QALY) or life-year (LY) gained. Analyses were conducted over a lifetime horizon. One-way deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in results. RESULTS: The rifaximin ± lactulose regimen provided added health benefits despite an additional cost versus lactulose monotherapy. Model results showed an incremental benefit of $29,161 per QALY gained and $27,762 per LY gained with rifaximin ± lactulose versus lactulose monotherapy. Probabilistic sensitivity analyses demonstrated that the rifaximin ± lactulose regimen was cost-effective ~99% of the time at a threshold of $50,000 per QALY/LY gained, which falls within the commonly accepted threshold for incremental cost-effectiveness. CONCLUSIONS: The clinical benefit of rifaximin, combined with an acceptable economic profile, demonstrates the advantages of rifaximin maintenance therapy as an important option to consider for patients at risk of recurrent HE. DISCLOSURES: This analysis was funded by Salix Pharmaceuticals, a division of Bausch Health US. Salix and Xcenda collaborated on the methods, and Salix, Xcenda, Jesudian, and Ahmad collaborated on the writing of the manuscript and interpretation of results. Bozkaya and Migliaccio-Walle are employees of Xcenda. Ahmad reports speaker fees from Salix Pharmaceuticals, unrelated to this study. Jesudian reports consulting and speaker fees from Salix Pharmaceuticals, unrelated to this study. The results from this model were presented at AASLD: The Liver Meeting 2014; November 7-11; Boston, MA.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy is a major neuropsychiatric complication of liver disease that affects 30% to 40% of cirrhotic patients. Hepatic encephalopathy is characterized by a brain dysfunction that is associated with neurologic complications. Those complications are associated with cognitive impairments, which negatively impacts patients' physical and mental health. In turn, hepatic encephalopathy poses a substantial economic and use burdens to the health care system. This article reviews the multidimensional aspects of the health care burden posed by hepatic encephalopathy.

Long-Term Management: Modern Measures to Prevent Readmission in Patients with Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a frequent indication for hospitalization and represents a common manifestation of portal hypertension and decompensated liver disease that contributes to hospital readmissions. Multiple new techniques are being evaluated to assist in preventing readmissions in these high-risk patients. Techniques to improve medication adherence are paramount. The use of telemedicine and on-demand patient assessment is likely to diminish hospitalizations for HE. Wearable technology has the potential to assist in HE diagnosis and prevent HE progression, with an anticipated diminution in hospital readmissions. This article discusses current and potential future techniques to improve outcomes in these vulnerable patients.

[Prognostic significance and economic burden of hepatic encephalopathy in liver cirrhosis in German hospitals based on G-DRG data]. / Mortalität und ökonomische Auswirkungen der hepatischen Enzephalopathie bei Leberzirrhose in deutschen Krankenhäusern auf der Basis von G-DRG-Kostendaten.

INTRODUCTION: Hepatic encephalopathy (HE) represents a frequent complication of liver cirrhosis with negative effects on patients' lives. The prevalence of clinical HE is estimated to be between 30-45 %. Regardless of its clinical and prognostic relevance HE is considered to be underdiagnosed. METHODS: Beyond a systematic analysis of mortality of HE, we investigated the economic impact and reimbursement situation for HE in patients with liver cirrhosis in Germany. For the retrospective analysis, anonymized data (2011-2015) concerning expenses and diagnoses (§â€Š21-4 KHEntgG) were obtained from 74 participating hospitals of the Diagnosis Related Groups (DRG) Project of the German Gastroenterological Association (DGVS). Furthermore, results were compared with case data from all German hospitals provided by the German Federal Authority on Statistics (Statistische Bundesamt (Destatis), Wiesbaden). RESULTS: In participating hospitals 59 093 cases with liver cirrhosis were identified of which 14.6 % were coded as having HE. Hospital mortality was threefold increased compared to cirrhosis-patients without HE (20.9 versus 7.5 %). Cases with cirrhosis as well as the proportion with HE increased over time. Compared to all patients with cirrhosis, reimbursement for HE patients produced a deficit (of up to 634 € for HE grade 4). DISCUSSION: Mortality is threefold increased in patients with cirrhosis when an additional HE is diagnosed. Hospitals participating in the DGVS-DRG-project coded 2 % more HE cases among their cirrhosis cases than the rest of hospitals either because of a selection bias for greater disease severity or because of better coding quality. At present, reimbursement for HE patients on the basis of F-DRG-system produced a deficit.

A validated risk model for prediction of early readmission in patients with hepatic encephalopathy.

INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a common complication in cirrhotics and is associated with an increased healthcare burden. Our aim was to study independent predictors of 30-day readmission and develop a readmission risk model in patients with HE. Secondary aims included studying readmission rates, cost, and the impact of readmission on mortality. MATERIALS AND METHODS: We utilized the 2013 Nationwide Readmission Database (NRD) for hospitalized patients with HE. A risk assessment model based on index hospitalization variables for predicting 30-day readmission was developed using multivariate logistic regression and validated with the 2014 NRD. Patients were stratified into Low Risk and High Risk groups. Cox regression models were fit to identify predictors of calendar-year mortality. RESULTS: Of 24,473 cirrhosis patients hospitalized with HE, 32.4% were readmitted within 30 days. Predictors of readmission included presence of ascites (OR: 1.19; 95% CI: 1.06-1.33), receiving paracentesis (OR: 1.43; 95% CI: 1.26-1.62) and acute kidney injury (OR: 1.11; 95% CI: 1.00-1.22). Our validated model stratified patients into Low Risk and High Risk of 30-day readmissions (29% and 40%, respectively). The cost of the first readmission was higher than index admission in the 30-day readmission cohort ($14,198 vs. $10,386; p-value <0.001). Thirty-day readmission was the strongest predictor of calendar-year mortality (HR: 4.03; 95% CI: 3.49-4.65). CONCLUSIONS: Nearly one-third of patients with HE were readmitted within 30 days, and early readmission adversely impacted healthcare utilization and calendar-year mortality. With our proposed simple risk assessment model, patients at high risk for early readmissions can be identified to potentially avert poor outcomes.

Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010-2014 National Inpatient Sample.

BACKGROUND: Hepatic encephalopathy (HE) is associated with substantial morbidity and mortality, contributing significant burden on healthcare systems. AIM: We aim to evaluate trends in clinical and economic burden of HE among hospitalized adults in the USA. METHODS: Using the 2010-2014 National Inpatient Sample, we identified adults hospitalized with HE using ICD-9-CM codes. Annual trends in hospitalizations with HE, in-hospital mortality, and hospital charges were stratified by the presence of acute liver failure (ALF) or cirrhosis. Adjusted multivariable regression models were evaluated for predictors of in-hospital mortality and hospitalization charges. RESULTS: Among 142,860 hospitalizations with HE (mean age 59.3 years, 57.8% male), 67.7% had cirrhosis and 3.9% ALF. From 2010 to 2014, total number of hospitalizations with HE increased by 24.4% (25,059 in 2010 to 31,182 in 2014, p < 0.001). Similar increases were seen when stratified by ALF (29.7% increase) and cirrhosis (29.7% increase). Overall in-hospital mortality decreased from 13.4% (2010) to 12.3% (2014) (p = 0.001), with similar decreases observed in ALF and cirrhosis. Total inpatient charges increased by 46.0% ($8.15 billion, 2010 to $11.9 billion, 2014). On multivariable analyses, ALF was associated with significantly higher odds of in-hospital mortality (OR 5.37; 95% CI 4.97-5.80; p < 0.001) as well as higher mean inpatient charges (122.6% higher; 95% CI + 115.0-130.3%; p < 0.001) compared to cirrhosis. The presence of ascites, hepatocellular carcinoma, and hepatorenal syndrome was associated with increased mortality. CONCLUSIONS: The clinical and economic burden of hospitalizations with HE in the USA continues to rise. In 2014, estimated national economic burden of hospitalizations with HE reached $11.9 billion.

Nationwide estimates and risk factors of hospital readmission in patients with cirrhosis in the United States.

BACKGROUND: The burden of cirrhosis on the healthcare system is substantial and growing. Our objectives were to estimate the readmission rates and hospitalization costs as well as to identify risk factors for 90-day readmission in patients with cirrhosis. METHODS: We conducted a weighted analysis of the 2014 Nationwide Readmission Database to identify adult patients with cirrhosis-related complications in the United States and assessed readmission rates at 30, 60 and 90 days post-index hospitalization. Predictors of 90-day readmissions were identified using weighted regression models adjusting for patient and hospital characteristics; the national estimate of hospitalization costs was also calculated. RESULTS: Of the 58 954 patients admitted with cirrhosis-related complications in 2014, 14 910 (25%) were readmitted within 90 days because of cirrhosis-related complications. The main causes of readmission were ascites (56%), hepatic encephalopathy (47%) and bleeding oesophageal varices (9%). Independent predictors of 90-day readmissions were male sex (adjusted OR [aOR]: 1.08, 95% CI, 1.04-1.13), age <60 (aOR: 1.27, 95% CI, 1.22-1.32), privately insured (aOR: 0.74, 95% CI, 0.70-0.77), having ≥3 comorbid conditions (aOR: 1.27, 95% CI, 1.14-1.42) and being discharged against medical advice (aOR: 1.41, 95% CI, 1.25-1.59). The weighted cumulative national cost estimate of the index admission was $1.8 billion, compared to $0.5 billion for readmission. CONCLUSIONS: A quarter of patients admitted with cirrhosis-related complications were readmitted within 90 days, representing a significant economic burden related to readmission of this population. Interventions and resource allocations to reduce readmission rates among cirrhotic patients is critical.

Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and Pharmacoeconomic Impact of Rifaximin.

BACKGROUND: Hepatic encephalopathy (HE), a common neurologic complication in cirrhosis, is associated with substantial disease and economic burden. Rifaximin is a non-systemic antibiotic that reduces the risk of overt HE recurrence and overt HE-related hospitalizations. OBJECTIVE: Our objective was to provide an overview of the direct HE-related costs and cost benefits of rifaximin, lactulose, and rifaximin plus lactulose. METHODS: A systematic review of PubMed and relevant meeting abstracts was conducted to identify publications since 1 January 2007 reporting economic data related to HE and rifaximin and/or lactulose. Further, a public database and published literature were used to estimate current costs of hospitalization for overt HE, and potential cost savings of HE-related hospitalizations with rifaximin. The methodological quality of included studies was evaluated using the Drummond checklist. RESULTS: A total of 16 reports were identified for inclusion in the systematic review. Globally, HE-related direct costs ranged from $US5370 to $US50,120 annually per patient. Rifaximin was associated with shorter hospital stays and reduced healthcare costs. Rifaximin also has the potential to reduce overt HE-related hospitalization risk by 50% compared with lactulose. Rifaximin was shown to have a favourable pharmacoeconomic profile compared with lactulose (based on the incremental cost-effectiveness ratio). CONCLUSIONS: In addition to its clinical benefits (e.g. reduction in the risk of recurrence of overt HE, overt HE-related hospitalizations, favourable adverse event profile), economic data are favourable for the use of rifaximin in patients with a history of overt HE.

Considerations for the cost-effective management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric complication commonly associated with liver disease, namely cirrhosis. The inability of the liver to metabolize ammonia results in a buildup of ammonia, which can cross the blood-brain barrier and cause significant neurocognitive impairment. Up to 80% of patients with cirrhosis will experience HE and a large proportion of these patients are at high risk of recurrent HE. There are several factors to consider when developing a cost-effective approach to managing HE, such as patient compliance, the adverse event (AE) profile of drug therapy, efficacy of drug therapy, and relative cost-benefits of drug therapy. Pharmacologic agents used for HE treatment and prevention are commonly associated with gastrointestinal AEs, namely diarrhea. While these AEs are mild in nature, they can be bothersome and lead to patient noncompliance, which increases the patient's risk of HE. Furthermore, the complex dosing schedule and self-titration requirement of lactulose, a first-line agent, can be confusing to a patient. A patient's noncompliance with self-titration may result in underuse, increasing the patient's risk of HE, or overuse, increasing the patient's risk of severe AEs. HE imposes a significant economic burden to the patient, patients' caregivers, healthcare systems, and society. HE not only negatively impacts a patient's morbidity and mortality, but also impacts the patient's psychological and social functioning and overall quality of life. HE can impact the patient's ability to work, resulting in reduced productivity and lost wages. A patient with HE may require hospitalization, which accounts for a substantial proportion of costs associated with HE. Given the social and financial burden of HE, cost-effective management of HE is crucial. Early prevention is important to minimize the societal and economic costs associated with HE.

[Clinical outcomes and hospital costs of hepatic encephalopathy: an analysis of "real life" data from Marche Region.] / Valutazione degli outcome clinici e dei costi ospedalieri dell'encefalopatia epatica conclamata: un'analisi sui dati "real life" della Regione Marche.

Hepatic encephalopathy (HE) describes a spectrum of potentially reversible neuropsychiatric changes observed in patients with hepatic dysfunction and/or portosystemic shunt. The aim of this study is to compare data from clinical trials and observational studies with Italian real-world (RW) data as for clinical outcomes; other aim is to evaluate economic burden of hepatic encephalopathy related to hospitalization for overt HE. The work is based on data from the Health Information Systems (SIS) of Marche Region, Italy (about 1.5 million patients) available for the period 2008-2014. 450 subjects were identified (62% men, mean age 68 years) with a first episode of overt HE (OHE) in the three-year period 2010-2012. The mortality in the index hospitalization was equal to 32.2%; the 2-year mortality rate for a specific cause was 24.3% while that for all cases was 33.1%. The proportion of patients discharged alive from the hospitalization index that in the following two years incurs in rehospitalization, correlated with OHE is on average 66.6%. These figures largely exceed those identified in clinical trials or observational studies. Assuming that the incidence of OHE cases observed in the Marche region is representative of the national one we could estimate a charge to the NHS equal to about € 200 million for hospital assistance in the first year from the OHE event.

Hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy.

AIM: To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission predictors. METHODS: We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from January 1, 2011 to December 31, 2013 (n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariate analyses were performed to describe variables associated with readmission. RESULTS: One hundred thirty-two patients (59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient visit. CONCLUSION: Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems.

Natural history of covert hepatic encephalopathy: An observational study of 366 cirrhotic patients.

AIM: To explore the natural history of covert hepatic encephalopathy (CHE) in absence of medication intervention. METHODS: Consecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE (OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed. RESULTS: A total of 366 patients (age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients (35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin < 30 g/L (HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine > 133 µmol/L (HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C (HR = 0.084, P < 0.001) and OHE history (HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE. CONCLUSION: CHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.

Optimal treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute or chronic liver disease with symptoms encompassing a continuum from mild confusion to coma. Both covert and overt HE have a significant impact on quality of life and healthcare related costs. The pathophysiology of HE is multifactorial and there is general consensus that ammonia and inflammation act synergistically to cause astrocyte swelling and cerebral edema. Current management strategies include the identification of precipitating factors and the initiation of pharmacologic therapies aimed at modulating intestinal flora and reducing levels of ammonia and other gut-derived toxins. Lactulose and rifaximin are two commonly used treatments for the management of HE. This article will review the optimal management of hepatic encephalopathy.

Benzodiazepine-associated hepatic encephalopathy significantly increased healthcare utilization and medical costs of Chinese cirrhotic patients: 7-year experience.

BACKGROUND AND OBJECTIVES: In cirrhosis, hypersensitivity to benzodiazepines (BZD) and precipitating hepatic encephalopathy (HE) have been reported. The aim of this study was to evaluate the safety, economic impact and modifiable factors that are associated with the excess risk of BZD-associated HE in cirrhotic patients. METHODS: Between July 2005 and March 2012, 1,612 Chinese cirrhotic patients with and without using long-t 1/2-BZD or short-t 1/2-BZD were enrolled and followed up for 6 months. RESULTS: Among BZD users, the per-person HE-related healthcare utilization and medical costs were found to have progressively increased from 2005 to 2012. Cirrhotic BZD users had a higher percentage of smoking, alcohol drinking, simultaneous consumption of non-BZD drugs, and had a higher incidence of non-cirrhotic chronic illness than non-BZD users. Multivariate analysis indicated that hypoalbuminemia (<3 g/dL), long-acting (t 1/2 > 12-h), high-dosage (>1.5 defined daily dose equivalents) and long-duration (>2-months) BZD use, carrier of variant genotypes (AG + GG) of GABRA 1 (rs2290732) and having the wild genotype (TT) of GABRG 2 (rs211037) were significant predictors of the development of BZD-associated HE in cirrhotic patients. Additionally, synergistic effects of the above significant predictors on BZD-associated HE risk could be identified. CONCLUSIONS: Our study confirms the clinical and economic impact of BZD-associated HE in cirrhotic BZD-users. Accordingly, extra caution is needed when treating cirrhotic BZD users with the above risk factors in order to avoid the BZD-associated HE in cirrhotic patients.

Antibiotics for the treatment of hepatic encephalopathy.

The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE.

In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a major complication of cirrhosis that causes substantial mortality and utilization of resources. METHODS: We analyzed 5 cycles of the Nationwide Inpatient Sample, conducted between 2005 and 2009, to determine national estimates of incidence, prevalence, inpatient mortality, severity of illness, and resource utilization for inpatients with HE. RESULTS: The yearly inpatient incidence of HE ranged from 20,918 (2005) to 22,931 (2009) (P = .2226), comprising approximately 0.33% of all hospitalizations in the United States. Over the 5-year period of analysis, mortality of inpatients with HE remained relatively stable, at 14.13%-15.61% (P = .062); however, the proportion of patients with major and extreme severity of illness increased (P < .0001). The average length of inpatient stay increased from 8.1 to 8.5 days (P = .019). The average total inpatient charges increased from $46,663 to $63,108 per case (P < .0001). Furthermore, total national charges related to HE increased from $4676.7 million (2005) to $7244.7 million (2009). In multivariate analysis, independent predictors of inpatient mortality included the number of diagnoses per admission (odds ratio [OR] = 1.022; 95% confidence interval [CI], 1.016-1.029 per diagnosis), number of procedures per admission (OR = 1.192 per procedure; 95% CI, 1.177-1.208), and major or extreme severity of illness (OR = 3.16; 95% CI, 2.84-3.50). The most important predictors of cost, charge, and length of stay were admission to a large, urban hospital; use of Medicaid or Medicaid as the payer; major or extreme severity of illness; number of diagnoses at discharge; and procedures per admission (P < .05). CONCLUSIONS: Resource utilization increased from 2005 to 2009 for patients discharged from US hospitals with the diagnosis of HE. The inpatient mortality rate, however, remained stable, despite a trend toward more severe disease.

Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the Americas.

BACKGROUND: Globally, hepatitis C virus (HCV) infects ∼3% of the population. The objective of this study was to review published work and determine the direct medical costs for diseases associated with HCV infection globally, with the exception of the US. METHODS: A systematic literature search was conducted to identify studies reporting the costs of hepatitis C sequelae between January 1990 and January 2011. Over 400 references were identified, of which 45 were pertinent. The costs were compiled, converted to US dollars, and adjusted to 2010 costs using the medical component of the consumer price index. RESULTS: The median cost of liver transplants was estimated at $139,070 ($15,430-$443,700), refractory ascites at $16,740 ($8990-$35,940), hepatocellular carcinoma (HCC) at $15,310 ($3370-$84,710), decompensated cirrhosis at $14,660 ($3810-$48,360), variceal hemorrhage at $12,190 ($3550-$46,120), hepatic encephalopathy at $9180 ($5370-$50,120), diuretic sensitive ascites at $3400 ($1320-$7470), compensated cirrhosis at $820 ($50-$2890), and chronic hepatitis C at $280 ($90-$1860). The variation among studies was mainly due to the methodology used to assess cost, local cost and government reimbursement, and country-specific treatment protocols. LIMITATIONS: All costs were adjusted to 2010 US dollars using the US medical component of the consumer price index (CPI) which may not reflect the change in medical costs in other countries. In addition, the costs, in the local currency were converted to US dollars in the year of the study. However, medical expenses may not vary with exchange rate, leading to artificial variations. Finally, there was no assessment of the quality of individual studies, which resulted in the same weighting to all studies. CONCLUSIONS: Hepatitis C imposes a high economic burden globally. Knowing the burden of HCV sequelae is useful for policy decisions as well as serving as a basis for determining the value of HCV screening and treatment.