Burden Of Chronic Liver Disease Research Articles

Assessment of fatigue and its impact in chronic liver disease

Patient reported outcomes (PROs) such as health related quality of life (HRQL) are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD such as primary biliary cholangitis (PBC), chronic hepatitis C viral infection (HCV) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also experience fatigue causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with PBC, HCV and MASLD. As such, a panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue highlighting that fatigue is comprised of peripheral (neuromuscular failure, often in conjunction with sub-maximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one’s ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for HCV and MASLD can improve levels of fatigue and HRQL, but current treatments for PBC do not seem to affect levels of fatigue. We conclude that obtaining PRO data to include HRQL and fatigue are essential for determining the comprehensive burden of CLD and its potential treatments. Impact and ImplicationsFatigue is a complex phenomenon associated with both a peripheral cause (neuromuscular failure and sub-maximal cardiorespiratory function) and a central cause (central nervous system dysfunction). Although fatigue is common among patients with CLD, it does not always correlate with the severity of the liver disease, but fatigue is related with significant decreases in patients’ health related quality of life (HRQL). Appreciating the impact of fatigue using validated self-report measurements is important to better understand the burden of CLD and the effectiveness of treatment.

Electronic sanitary database: a new potential tool to identify occult chronic liver disease in general population

Chronic liver disease (CLD) is a leading global cause of mortality, morbidity, and healthcare resource utilization. However, the burden of CLD is underestimated because the course of the disease is often asymptomatic until clinical decompensation and the development of life-threatening complications. In this study, we assessed the use of available blood tests from electronic medical records for identifying individuals with undiagnosed CLD in the general population. We analyzed a total of 202,529 blood tests obtained from 99,848 adults recorded in the Electronic Health Records of the Padova Teaching Hospital. Transaminases levels > 1.5 times the normal value indicated occult CLD, while platelet counts < 120,000/μL identified occult cirrhosis. We characterized patients using Italian Medical Exemptions (IME), excluding oncologic cases. Overt and occult cirrhosis prevalence was 1% and 4.18%, respectively, while overt and occult CLD affected 2.85% and 4.61% of the population. The epidemiology of patients with overt and occult cirrhosis was similar but significantly different from that of the controls. Among subjects aged 60–70 years, working disability was twofold higher in those with occult cirrhosis compared to those with overt cirrhosis. Occult CLD and cirrhosis had higher prevalence rates than diagnosed cases in the general population. Electronic medical record data may serve as a valuable tool for CLD identification, potentially reducing cirrhosis development and clinical decompensation. This, in turn, may lead to a decrease in the economic impact on the healthcare system.

Preventive hepatology at AIIMS Rishikesh: Delivering comprehensive and integrated care for liver diseases in Northern state of India.

Globally, liver diseases accounts for 4% of all deaths. Annually, over 2 million deaths occur due to preventable causes of chronic liver diseases and liver cancer like fatty liver diseases (alcoholic or non alcoholic) and viral hepatitis B and C. The burden of chronic liver diseases are increasing, and the epidemiology and demographics of people affected by these diseases are changing. Policy changes, vaccination, screening, lifestyle changes and public health awareness is the key to curb down liver disaeses. To achieve the ultimate goal of reducing mortality and linkage to care for those who need specialized care for liver disease, it is vital to have dedicated preventive hepatology clinics in sync with existing liver or gastroenterology clinics at tertary care level.

Viral hepatitis B and C infections in adolescents born pre- and post-hepatitis B vaccine introduction in Calabar, Nigeria

Hepatitis B and C Virus (HBV, HCV) infections are major contributors to the burden of chronic liver diseases globally. In a bid to curb the HBV infection, the Nigerian Government introduced the HBV vaccine into the National Program on Immunization (NPI) in 2004.This study aimed to determine the prevalence and associated factors of HBV and HCV infections among adolescents in secondary schools in Calabar, Cross River State, South-South Nigeria, in the pre- and post-vaccination era. This was a school-based, cross-sectional study. Six hundred and sixty secondary school adolescents, aged 10-20 years, were recruited using multi-staged sampling technique. Hepatitis B Surface Antigen (HBsAg) and HCV antibody screening were done respectively on the study participants using rapid chromatographic immunoassay method. The relationship between sociodemographic variables and Hepatitis B infection were described. A p-value of less than 0.05 was considered significant. The mean age of the participants was 14.85±2.11 years. Six participants were positive for HBsAg, giving an overall prevalence of 0.9%. The positive adolescents were from public schools, and the age group mostly positive was 16 years and above (2.1%). None of the screened adolescents was positive for HCV antibody. Though the prevalence of HBV infection was low, most of those positive were delivered before the introduction of the HBV vaccine into the NPI schedule. Modalities to vaccinate young people delivered before the introduction of Hepatitis B vaccine into the NPI schedule should be developed.

Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.

The burden of chronic liver disease is rising substantially worldwide. Fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the common pathway leading to cirrhosis, and limited treatment options are available. There is increasing evidence suggesting the role of cellular stress responses contributing to fibrogenesis. This Review provides an overview of studies that analyse the role of cellular stress in different cell types involved in fibrogenesis, including hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells and macrophages.

The burden of chronic liver disease in west Africa: a time for action

The burden of chronic liver disease in west Africa: a time for action

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed. To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population. This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023. Regular statin use. Primary outcomes were liver disease and HCC development as well as liver-associated death. A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02). This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

The future of Hepatology Communications

The future of Hepatology Communications

Liver Function Tests in Hepatitis C Patients of Local Population of Lahore

Hepatic fibrosis is a chronic disease that results from hepatitis C infection. The tests used to screen for chronic liver disease are known as serum biochemical liver tests (LTs) (alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase). Objectives: To determine the prevalence and etiologies of abnormal LTs in the population of Lahore, Pakistan. To determine whether there is any correlation of HCV infection and viral load to the clinical parameters such as ALT, AST, ALP, bilirubin, patient's age and gender. Methods: Liver function tests (ALT, AST, and Bilirubin) were carried out using standard kits and a regular chemical analyzer in a photometric manner. Results: In our research, we gathered information from 80 patients, out of whom 27 women and 53 men. HCV was more common in the adult population aged 30 years or older and in men than in women. These individuals had elevated levels of several biochemical markers as ALT, AST, and ALP. Conclusions: Based on the results of this research and our investigation, we saw instances of viral hepatitis being diagnosed in asymptomatic patients with abnormal LFTs. The findings of the present investigation showed that men and patients under the age of 30 in Lahore had a significant frequency of abnormal LTs. Test results reveal biochemical markers at particularly elevated levels. Implementing initiatives to lessen the potential burden of chronic liver disease may benefit from knowing the estimated prevalence and etiologies of aberrant LTs (CLD).

WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN.

Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

Infectious hepatitis

Infectious hepatitis describes inflammation of the liver due to transmissible viruses. The five most common viruses recognised are classed alphabetically as A, B, C, D and E. These different viruses cannot be differentiated clinically, but a focused history and examination can provide clues towards aetiology, guide appropriate investigations and allow for identification of complications. Hepatitis A and E are typically enterically transmitted and generally follow a mild and self-limiting course. Hepatitis B, C and D are parenterally transmitted and collectively account for a large burden of chronic liver disease globally. This article will cover clinical assessment and management of patients with viral hepatitis A–E. Although there are numerous other types of infectious hepatitis, labelled ‘non-A–E hepatitis’, they are rare and not routinely tested for in clinical practice so are not covered in this article. We will also not cover viruses with more systemic effects which can cause hepatitis but are not specific to the liver, such as Epstein– Barr virus and cytomegalovirus.

Nonalcoholic Fatty Liver Disease: Current Global Burden.

The map and global disease burden of chronic liver diseases are markedly changing, with nonalcoholic fatty liver disease (NAFLD) becoming the most common cause of liver diseases coinciding with the current epidemics of obesity, type 2 diabetes, and metabolic syndrome. Understanding the incidence and prevalence of NAFLD is critical because of its linkage to a significant economic burden of hospitalization and changing patterns in consequences, such as liver transplantation. Moreover, the long-term average health care expenses of NAFLD patients have exceeded those of other liver diseases. To lessen the imminent burden of NAFLD, immediate actions to raise worldwide awareness and address metabolic risk factors are required. This review summarizes key data about the global disease burden of NAFLD, modifiable and nonmodifiable risk factors, and current preventive approaches.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

BackgroundThe development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease.MethodsThis study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program.DiscussionThis study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country.Trial registrationThis study is registered on Clinicaltrials.gov (NCT03789825).

Financial burden in adults with chronic liver disease: A scoping review.

The economic burden of chronic liver disease is rising; however, the financial impact of chronic liver disease on patients and families has been underexplored. We performed a scoping review to identify studies examining financial burden (patient/family health care expenditures), financial distress (material, behavioral, and psychological consequences of financial burden), and financial toxicity (adverse health outcomes of financial distress) experienced by patients with chronic liver disease and their families. We searched MEDLINE, Embase, Cochrane Library, and the Web of Science online databases for articles published since the introduction of the Model for End-Stage Liver Disease score for liver transplantation allocation in February 2002 until July 2021. Final searches were conducted between June and July 2021. Studies were included if they examined the prevalence or impact of financial burden or distress among patients with chronic liver disease and/or their caregivers. A total of 19 observational studies met inclusion criteria involving 24,549 patients and 276 caregivers across 5 countries. High rates of financial burden and distress were reported within the study populations, particularly among patients with hepatic encephalopathy, hepatocellular carcinoma, and liver transplantation recipients. Financial burden and distress were associated with increased pre- and posttransplantation health care utilization and poor health-related quality of life as well as caregiver burden, depression, and anxiety. None of the included studies evaluated interventions to alleviate financial burden and distress. Observational evidence supports the finding that financial burden and distress are underrecognized but highly prevalent among patients with chronic liver disease and their caregivers and are associated with poor health outcomes. There is a critical need for interventions to mitigate financial burden and distress and reduce financial toxicity in chronic liver disease care.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases.

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

Prevalence and risk factors of Hepatitis D virus antibody among asymptomatic carriers of Hepatitis B virus: a community survey.

Hepatitis D virus (HDV) can cause a chronic infection in the presence of hepatitis B surface antigen and contribute to the burden of chronic liver disease especially in regions where chronic hepatitis B virus (HBV) infection is endemic. To determine the prevalence and risk factors of HDV among asymptomatic carriers of HBsAg in Cross River State, Nigeria. This was a cross-sectional study conducted among apparently healthy adults resident in Cross River State, Nigeria. A structured questionnaire was used to collect socio-demograhic data and risk factors for HBV/HDV infection. Participants blood samples were screened for HBsAg. Samples that were HBsAg positive were further screened for anti-HDVIgM. Statistical analysis was performed using statistical package for social sciences (SPSS) version 20. A total of 90 HBsAg positive samples were assayed. The prevalence of anti-HDV IgM was 5.6% (95% CI 1.1-10.1). The HDV positive subjects were mostly females (80%), reported family size of >5 members (80%), had female circumcision (75%) and took injections from Non-certified health care practitioners (NCHCPs). None of the assessed risk factors were significantly associated with HDV infection (p >0.05). Hepatitis D virus is moderately prevalent amongst asymptomatic HBsAg carriers in Cross River State, Nigeria.

Review article: post-TIPSS hepatic encephalopathy-current knowledge and future perspectives.

In light of the global rise in the burden of chronic liver diseases and liver cirrhosis, the number of patients suffering from decompensation events is expected to increase. Transjugular intrahepatic portosystemic shunts (TIPSS) provide effective long-term symptom control and may prolong transplant-free survival in portal hypertension-driven recurrent ascites and variceal bleeding. New-onset or recurrent hepatic encephalopathy (HE) after TIPSS insertion (post-TIPSS HE) represents the most severe post-interventional complication. To provide insight into the epidemiology and risk factors for post-TIPSS HE and scrutinize the current state of the art in treatment and drug therapy options. We conducted a literature search on post-TIPSS HE in patients with liver cirrhosis. Post-TIPSS HE occurs in up to 54.5% of cases and particularly early recurrent HE is associated with a dismal prognosis. In recent years, several risk factors for the development of post-TIPSS HE have been identified. These include not only parameters reflecting liver function (model for end-stage liver disease score/Child-Pugh score) as well as cognitive dysfunction caused by minimal HE but also extrahepatic factors such as sarcopenia and common medications such as proton pump inhibitors. In addition, new data on the benefit of rifaximin and of smaller stent grafts emerged and may improve the prevention of post-TIPSS HE. Careful selection of TIPSS candidates is of utmost importance to reduce the risk of post-TIPSS HE. In this narrative review, we provide a concise overview of the current epidemiology and risk factors of the treatment options for post-TIPSS HE.

Old-fashioned and newly discovered biomarkers: the future of NAFLD-related HCC screening and monitoring

Nonalcoholic fatty liver disease (NAFLD) is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis (NASH), which may progress into cirrhosis and hepatocellular carcinoma (HCC). HCC represents the most common liver cancer, and it is a leading cause of death worldwide with an increasing trend for the future. Due to late diagnosis, non-responsiveness to systemic therapy, and high cancer heterogeneity, the treatment of this malignancy is challenging. To date, liver biopsy and ultrasound (US) are the gold standard procedures for HCC diagnosis and surveillance, although they are not suitable for mass screening. Therefore, it is impelling to find new, less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence. Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset. Furthermore, epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions. The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs (ctDNAs), microRNAs (miRNAs), and noncoding RNAs (ncRNAs), which are involved in several pathological processes that feature cancer, including cell growth, survival, and differentiation, thus representing appealing biomarkers for HCC. Therefore, this review discusses the current options for HCC surveillance, focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.

Silymarin for Treating Toxic Liver Disease: International Consensus Recommendations

Silymarin for Treating Toxic Liver Disease: International Consensus Recommendations

Global burden of NAFLD and chronic liver disease among adolescents and young adults.

The causes of chronic liver disease (CLD) among adults have changed. Data are lacking on trends among youth. We determined the trends and changes in the global burden of CLD among adolescents and young adults using Global Burden of Disease (GBD) data (2009-2019). The GBD study estimation methods were used to assess CLD prevalence, incidence, and deaths (21 GBD regions). Annual percent change (APC) calculation by joinpoint regression modeling. Age groups were 15-19, 20-24, and 25-29 years old. Globally in 2019, the 15-29 group accounted for 17.2% (0.29 billion) of CLD prevalent cases, 11.2% (n = 232,072) CLD incident cases, and 3.8% (n = 55,515) CLD deaths. Between 2009 and 2019, CLD prevalence rate increased annually among 25-29 (APC = +0.41%, p < 0.001); remained stable among 20-24 (APC = +0.02%, p = 0.582); and decreased among 15-19 (APC = -2.13%, p < 0.001). CLD prevalence increases were driven by the proportion with NAFLD (15-19: 40.8% to 52.9%, p < 0.001); 20-24: 57.6% to 62.7%, p < 0.001); and 25-29: 66.9% to 70.1%, p < 0.001); the proportion with HBV decreased across all age groups. NAFLD prevalence worsening trend (APC ≥ 0%) was global. Overall CLD death rate decreased annually in all age groups, driven by the decrease in the proportion with HBV [aged 15-19 (from 5.90% to 5.20%, p < 0.001); aged 20-24 (from 18.62% to 16.37%, p < 0.001); and aged 25-29 (from 28.69% to 25.28%, p < 0.001)]; from 2015 to 2019, CLD death rate for HCV (APC = +1.46%) and NAFLD (APC = +2.26%) increased. Over the past decade, the causes of CLD among 15-29-year-olds have shifted: viral hepatitis remains the most common cause of CLD deaths, but the global burden of HBV incidence is decreasing, whereas NAFLD is the main driver for increased CLD incidence.