Burden Of Chronic Liver Disease Research Articles

Direct and Indirect Economic Burden of Chronic Liver Disease inthe United States.

Chronic liver (CLD) is a major public health concern. We assessed its effects on quality of life and work productivity, as well as its economic burden in the United States. We performed a cross-sectional study of data from the Medical Expenditure Panel Survey (MEPS; 2004-2013). We extracted participants' sociodemographic parameters and medical histories. Subjects with CLD were identified based on Clinical Classification Software codes.MEPS participants were compared between those with and without CLD, and then between employed and unemployed patients with CLD. Outcomes were quality-of-life scores, employment, and health care use. We collected data from 230,406 adult participants (age, ≥18 y) in the MEPS; 1846 had current CLD (36.7% with viral hepatitis and 5.3% with liver cancer). Individuals with CLD were less likely to be employed (44.7% vs 69.6% patients without CLD), were not working owing to illness/disability (30.5% vs 6.6% without CLD), lost more work because of disability (10.2 vs 3.4 d without CLD), and had more health care use, producing greater health care expenses ($19,390 vs $5567/y without CLD) (all P < .0001). Patients with CLD also had more comorbidities and worse self-reported general and mental health status, and reported more health-related limitations in their daily activities than individuals without CLD (all P < .0001). They also indicated more psychologic distress and depressive symptoms and had a lower quality oflife and health utility scores (P < .0001). In multivariate analysis, after adjustment for sociodemographic factors and comorbidities, the presence of CLD was an important predictor of unemployment (odds ratio, 0.60; 95% confidence interval, 0.50-0.70), annual health care expenditure (β = $9503 ± $2028), and impairment in all aspects of health-related quality of life (all P < .0001). In patients with CLD, the presence of liver cancer had the most profound impact on health care expenditures (β= $17,278 ± $5726/y) and physical health (β= -7.2 ± 1.7 for SF-12 physical component) (all P < .005). In a cross-sectional analysis of MEPS participants, we associated CLD with large economic and quality-of-life burdens.

Non-viral liver disease burden in HIV-monoinfected individuals: a longitudinal observational retrospective cohort study

ABSTRACTRecent advances in antiviral therapy have improved outcomes in HIV-positive individuals co-infected with hepatitis B and C virus (HBV/HCV). Our aim was to assess prevalence and predictors of chronic liver disease (CLD) due to the metabolic syndrome (MS), alcohol and antiretrovirals (ARVs) use in HIV-monoinfected individuals. This was a retrospective cohort study (2005–2012). HIV-positive patients with negative HBV/HCV serology and at least two elevated alanine aminotransferase (ALT) levels six months apart were included. Data are presented as mean ± SD or percentage. Despite negative viral serology, 27% (1047/3872) of HIV-positive individuals had persistently elevated ALT. Only 243 (23.2%) were investigated (by imaging in the majority, only 58 undergoing liver biopsy/transient elastography). CLD was identified in 66.2%, this being clinically significant in one in four individuals. Potential CLD risk factors were alcohol (44.2%), hepatotoxic ARVs (74.1%) and MS risk factors (68%) with 68.7% having >1 risk factor. On multivariate logistic regression analysis serum triglyceride (OR 1.482, 95% CI 1.053–2.086, p = .024) was the only independent predictor of CLD. Overall, 4.3% were referred to Hepatology services. In conclusion, less than 6% of HIV-monoinfected individuals with persistently elevated ALT undergo objective assessment of hepatic fibrosis. Despite non-stringent criteria, some degree of non-viral CLD is identified in approximately two-thirds of those investigated, risk factors being synonymous with those for the MS. This increasing yet under-recognised non-viral CLD burden warrants timely recognition to prevent long-term morbidity and mortality.

Hepatocellular Carcinoma: the Impact of NAFLD

The burden of chronic liver diseases including hepatocellular carcinoma (HCC) due to non-alcoholic steatohepatitis (NASH) and metabolic syndrome (MS) is increasing worldwide. Moreover, MS and its components act as co-factors in HCC development in patients with other chronic liver diseases due to high alcohol intake or hepatitis B or C infection. Patients with NASH-related HCC are frequently older; their tumors are more frequently diagnosed in non-cirrhotic livers and at an advanced stage compared to HCC due to other etiologies. Patients with MS appear also to be at risk of post-operative complications after liver resection and transplantation. However, after adjustment for tumor burden and severity of the underlying liver disease, long-term outcomes appear to be similar for NASH-related HCC and HCC due to other etiologies. Research on preventive strategies, screening programs for patients with NASH without cirrhosis but at high risk of HCC development, and new therapeutic strategies are warranted in order to respond to this emerging menace.

The societal burden of chronic liver diseases: results from the COME study

ObjectiveChronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with...

Palliative Care in Decompensated Cirrhosis: The VA Experience

Introduction: The burden of chronic liver disease in US is significant and at present cirrhosis with complications is amongst the top ten killers. Only a small subset of patients referred for liver transplant actually receive it. The remaining often have a progressive disease course characterized by frequent hospitalizations, ICU admissions, invasive interventions for life threatening complications and have to undergo great amount of physical, emotional and financial distress. Prior studies have shown patients ‘at risk of dying' from complications of cirrhosis are candidates for palliative care. Our aim was to investigate how frequently patients with decompensated cirrhosis received referral to palliative care. We also explored timing of such referral Methods: Retrospective chart review was performed and any patient between 18-80 years of age with decompensated cirrhosis (development of one or more complications of ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatocellular cancer) was included. Data was collected on demographic profile, etiology of cirrhosis, labs for MELD and CPT score, number of hospitalizations and invasive interventions and whether referred for liver transplant or if there was ‘end of life discussion' or referral to palliative care. Results: 62 patients (mean age 61) with ESLD were included. Alcohol and Hepatitis C were the predominant etiologies, followed by NASH. The mean MELD score was 18.9. Of these 37% were referred for palliative care while remaining 63% were neither referred to palliative care nor had any ‘end of life' discussion documented in chart. 87% of patients referred for palliative care died. 50% died during an acute hospitalization and for majority of the patients palliative care was involved only in the last few days prior to death. Majority of the patients with decompensated cirrhosis were either not eligible or died while waiting for liver transplant. Conclusion: Patients with ESLD continued to receive curative efforts until the ‘end of life'. For majority of patients palliative or hospice care is either not provided or provided only in the last one or two weeks of life when hope of liver transplant or survival is low. Since only a minority of patients listed for transplant actually receive a transplant, simultaneous provision of curative efforts and palliative care while awaiting liver transplant has the potential to improve quality of life for patients and their families.

Living donor liver transplantation in Taiwan-challenges beyond surgery.

Taiwan has a high prevalence of hepatitis B and C viral infections, and consequently a high burden of chronic liver diseases. Liver transplantation (LT) began in Taiwan in 1984, and living donor liver transplantation (LDLT) in 1994. Education and collaboration between physicians on a national and international scale were important factors in the development of transplantation in East Asia. Technical innovations in donor hepatectomy, vascular and biliary reconstruction, and interventional radiology, perioperative management of transplant patients and development of associated specialties have enabled achievement of excellent results after both adult and pediatric LDLT. The establishment of rigorous protocols to withstand strict medico-legal scrutiny, combined with technical excellence has contributed to excellent surgical outcomes. The socioeconomic development of Taiwan and the first nationwide hepatitis B vaccination program in the world have also contributed to the decrease in disease burden and improvement of quality of healthcare. This article examines the factors enabling the development of LT in Taiwan, the innovations that have contributed to excellent outcomes, and indicates the future prospects of LDLT in Taiwan.

Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations.

BackgroundThe global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations.ResultsDNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008).ConclusionsThese results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0255-3) contains supplementary material, which is available to authorized users.

Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes

Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 700,000 people. Gender-matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long-term outcomes of all three groups, and compared T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver-related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts--when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension. Type 1 diabetes is associated with a previously unrecognized burden of CLD and its complications.

Sticker shock and the price of new therapies for hepatitis C: Is it worth it?

Sticker shock and the price of new therapies for hepatitis C: Is it worth it?

Continuing Medical Education: March 2014

The Contribution of Viral Hepatitis to the Burden of Chronic Liver Disease in the United States The American College of Gastroenterology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American College of Gastroenterology designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The Contribution of Viral Hepatitis to the Burden of Chronic Liver Disease in the United States

Chronic liver disease (CLD) is increasingly recognized as a major public health problem. However, in the United States, there are few nationally representative data on the contribution of viral hepatitis as an etiology of CLD. We applied a previously used International Classification of Diseases, Ninth Revision, Clinical Modification-based definition of CLD cases to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey databases for 2006-2010. We estimated the mean number of CLD visits per year, prevalence ratio of visits by patient characteristics, and the percentage of CLD visits attributed to viral hepatitis and other selected etiologies. An estimated 6.0 billion ambulatory care visits occurred in the United States from 2006 to 2010, of which an estimated 25.8 million (0.43%) were CLD-related. Among adults aged 45-64 years, Medicaid and Medicare recipients were 3.9 (prevalence ratio (PR)=3.9, 95% confidence limit (CL; 2.8, 5.4)) and 2.3 (PR=2.3, 95% CL (1.6, 3.4)) times more likely to have a CLD-related ambulatory visit than those with private insurance, respectively. In the United States, from 2006 to 2010, an estimated 49.6% of all CLD-related ambulatory visits were attributed solely to viral hepatitis B and C diagnoses. In this unique application of health-care utilization data, we confirm that viral hepatitis is an important etiology of CLD in the United States, with hepatitis B and C contributing approximately one-half of the CLD burden. CLD ambulatory visits in the United States disproportionately occur among adults, aged 45-64 years, who are primarily minorities, men, and Medicare or Medicaid recipients.

Vertical transmission of hepatitis C virus: Current knowledge and perspectives.

Hepatitis C virus (HCV) infection is a major global health issue. Infection by the HCV can cause acute and chronic liver diseases and may lead to cirrhosis, hepatocellular carcinoma or liver failure. The World Health Organization estimates that approximately 3% of the world population have been infected with HCV and the worldwide prevalence is between 1% and 8% in pregnant women and between 0.05% and 5% in children. Following the introduction of blood product screening, vertical transmission becomes the leading cause of childhood HCV infection. The prevalence of pediatric HCV infection varies from 0.05% to 0.36% in developed countries and between 1.8% and 5% in the developing world. All children born to women with anti-HCV antibodies should be checked for HCV infection. Though universal screening is controversial, selective antenatal HCV screening on high-risk populations is highly recommended and should be tested probably. Multiple risk factors were shown to increase the possibility of HCV vertical transmission, including coinfections with human immunodeficiency virus, intravenous drug use and elevated maternal HCV viral load, while breastfeeding and HCV genotypes have been studied to have little impact. At present, no clinical intervention has been clearly studied and proved to reduce the HCV vertical transmission risk. Cesarean section should not be recommended as a procedure to prevent vertical transmission, however, breastfeeding is generally not forbidden. The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to reduce the burden of chronic liver disease. Future researches should focus on the interruption of vertical transmission, developments of HCV vaccine and direct-acting antivirals in infancy and early childhood.

Chronic hepatitis C virus infection and atherosclerosis: Clinical impact and mechanisms

Hepatitis C virus (HCV) infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases, which are associated with excess mortality. Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis, heart failure and stroke. In contrast, findings from studies addressing coronary artery disease and HCV have yielded conflicting results. Therefore, meta-analytic reviews and prospective studies are warranted. The pathogenic mechanisms connecting HCV infection, chronic liver disease, and atherogenesis are not completely understood. However, it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls, liver steatosis and fibrosis, enhanced and imbalanced secretion of inflammatory cytokines, oxidative stress, endotoxemia, mixed cryoglobulinemia, perturbed cellular and humoral immunity, hyperhomocysteinemia, hypo-adiponectinaemia, insulin resistance, type 2 diabetes and other components of the metabolic syndrome. Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection. Currently, it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality; moreover, interferon-based treatment appears to decrease the risk of ischemic stroke.

Descriptive epidemiology of chronic liver disease in northeastern Italy: an analysis of multiple causes of death

BackgroundThe analysis of multiple causes of death data has been applied in the United States to examine the population burden of chronic liver disease (CLD) and to assess time trends of alcohol-related and hepatitis C virus (HCV)-related CLD mortality. The aim of this study was to assess the mortality for CLD by etiology in the Veneto Region (northeastern Italy).MethodsUsing the 2008–2010 regional archive of mortality, all causes registered on death certificates were extracted and different descriptive epidemiological measures were computed for HCV-related, alcohol-related, and overall CLD-related mortality.ResultsThe crude mortality rate of all CLD was close to 40 per 100,000 residents. In middle ages (35 to 74 years) CLD was mentioned in about 10% and 6% of all deaths in males and females, respectively. Etiology was unspecified in about half of CLD deaths. In females and males, respectively, HCV was mentioned in 44% and 21% and alcohol in 11% and 26% of overall CLD deaths. A bimodal distribution with age was observed for HCV-related proportional mortality among females, reflecting the available seroprevalence data.ConclusionsMultiple causes of death analyses can provide useful insights into the burden of CLD mortality according to etiology among different population subgroups.

The State of Hepatitis B and C in the Mediterranean and Balkan Countries: Report from a Summit Conference

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Covering the Cover

Covering the Cover

Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence

In efforts to inform public health decision makers, the Global Burden of Diseases, Injuries, and Risk Factors 2010 (GBD2010) Study aims to estimate the burden of disease using available parameters. This study was conducted to collect and analyze available prevalence data to be used for estimating the hepatitis C virus (HCV) burden of disease. In this systematic review, antibody to HCV (anti-HCV) seroprevalence data from 232 articles were pooled to estimate age-specific seroprevalence curves in 1990 and 2005, and to produce age-standardized prevalence estimates for each of 21 GBD regions using a model-based meta-analysis. This review finds that globally the prevalence and number of people with anti-HCV has increased from 2.3% (95% uncertainty interval [UI]: 2.1%-2.5%) to 2.8% (95% UI: 2.6%-3.1%) and >122 million to >185 million between 1990 and 2005. Central and East Asia and North Africa/Middle East are estimated to have high prevalence (>3.5%); South and Southeast Asia, sub-Saharan Africa, Andean, Central, and Southern Latin America, Caribbean, Oceania, Australasia, and Central, Eastern, and Western Europe have moderate prevalence (1.5%-3.5%); whereas Asia Pacific, Tropical Latin America, and North America have low prevalence (<1.5%). The high prevalence of global HCV infection necessitates renewed efforts in primary prevention, including vaccine development, as well as new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival for those who already have evidence of liver disease.

Upper Reference Limits for Aminotransferase Activities and the Prevalence of Elevated Aminotransferase Activities in a Korean Population

Despite suggestions to lower the upper reference limits (URL) for aminotransferase activities to increase the detection of liver disease, there is no generally accepted URL in the general Korean population. We set the URL for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the 97.5th percentile in a population at low risk for liver disease (n=3316; negative HBs antigen, low alcohol intake, normal waist circumference, normal lipid or carbohydrate metabolism, and absence of medication use) derived from the 2007 to 2009 Korean National Health and Nutrition Examination Survey (KNHANES; n=16,608). The URLs for ALT activity were 53 IU/L for men and 30 IU/L for women, and the corresponding limits for AST activity were 37 IU/L for men and 29 IU/L for women. The age-adjusted prevalence of the elevated ALT activity was 8.6% [95% confidence interval (CI), 8.2%-9.1%] in the 2007 to 2009 KNHANES and 6.9% (95% CI, 6.3%-7.5%) in the 2001 KNHANES, a relative increase of 24.6% (P<0.05). This increase was concentrated among those aged 20 to 29, with a relative increase of 66.7%, and those aged 30 to 39, with a relative increase of 54.4%. There was no significant change in the prevalence of elevated AST activity. The URL for ALT activity among the general Korean population is clearly higher than recently proposed thresholds. The trajectory of the increasing prevalence of elevated ALT activity heralds an increased burden of chronic liver disease in the future Korean population.

Impact of restricting access to high-cost medications for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, and its incidence is increasing in the West, including the UK, with the increasing burden of chronic liver disease. Until recently, systemic treatment options for advanced disease were limited. However, randomized clinical trials have demonstrated that the multikinase inhibitor sorafenib prolongs survival in appropriately selected patients, and this drug has become the standard of care for patients with advanced HCC. However, a single-technology appraisal by the NICE recommended that the UK National Health Service should not fund sorafenib on the grounds of cost–effectiveness. A number of other novel agents and combinations are currently in clinical trials, the results of which may further expand the treatment options and indications for systemic therapy in HCC. This review discusses the impact of restricting access to high-cost medications for patients with HCC in the UK, and describes potential strategies and future directions that may improve the cost–effectiveness of such drugs. It also describes the potential impact, pending national guidance, of variations in local funding decision-making on patient outcomes.

Managing systemic symptoms in chronic liver disease

Improved medical management and the changing disease demographic mean that the majority of patients with chronic liver disease are living with the disease rather than dying from it. Historically, the perception has been that the impact of chronic liver disease is related entirely to the consequences of endstage liver disease; however, more recently a number of systemic symptoms have been recognised that can occur at any point in the natural history of chronic liver disease and which can be associated with functional impairment and reduced quality of life. The most characteristic of these systemic symptoms is fatigue, which frequently associates with sleep disturbance and autonomic dysfunction, particularly manifest as abnormality of blood pressure regulation. Cognitive symptoms can occur even in non-cirrhotic patients. Falls can present in patients with autonomic dysfunction, complicated by the presence of peripheral muscle strength problems. Importantly for clinicians managing chronic liver disease, the severity of these systemic symptoms is typically not related to liver disease severity, and therefore despite optimal liver disease management, patients can often continue to experience debilitating symptoms. The similarity in systemic symptoms between different chronic liver diseases (and indeed chronic inflammatory conditions affecting other organs) suggests the possibility of shared pathogenetic processes and raises the possibility of common management strategies, although further research is urgently needed to confirm this. In primary biliary cirrhosis, where our understanding of systemic symptoms is arguably most developed, structured management strategies have been shown to improve the quality of life of patients. It is highly likely that similar approaches will have comparable benefits for other chronic liver disease groups. Here, we review the current understanding of systemic symptoms in chronic liver disease and offer recommendations regarding the successful management of these symptoms. Critical for successful treatment is use of a structured and systematic approach to management in which all contributing factors are addressed in an organised fashion. We believe that such a systematic approach, when applied to research as well as to clinical management, will allow us to reduce the overall burden of chronic liver disease, improve quality of life and enhance functional ability.