Harnessing Oleanolic Acid as A Modulator of Metabolic Nuclear Receptors (preprint)

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to those NRs modulation, OA exhibited prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Idiopathic or Drug Induced Autoimmune HepatitisCan We Draw a Line? (preprint)

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Aging Exacerbates Oxidative Stress and Liver Fibrosis in an Ani-Mal Model of Down Syndrome (preprint)

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Changes in the Epidemiology of Hepatocellular Carcinoma in Carinthia, Austria, 2012–2023 (preprint)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths and remains a major burden on health-care systems worldwide. The incidence of HCC continues to rise globally, despite preventative efforts being made. Aims: This study aimed to investigate epidemiological changes observed in the aetiology and survival outcomes of HCC patients at Klinikum Klagenfurt am Wörthersee between 2012 and 2023. Methods: This was a retrospective, single-centre cohort observational study. Two time-periods (2012-2017 and 2018-2023) were created to enable comparison between the respective intervals. Results: More patients were diagnosed with HCC during the second time-period, proving that the incidence of HCC is rising or the referral patterns changing. The median age of diagnosis was 72.5 years (SD 8.6). Patients were on average 2 years younger in the second time-period compared to the first (p = 0.042). Alcohol remained the leading underlying aetiology of HCC and no statistically significant change was seen over time (p = 0.353). Nevertheless, a clear upward trend in the number of NASH cases was evident over time (n = 15, n = 28 respectively). Nearly half of the patient population did not have a raised AFP at the time of diagnosis. The survival time for HCC patients remained similar between time-periods, with a median overall survival time of 20.5 months (95% CI 16.8-24.2, p = 0.841), despite improvements in management strategies and the availability of new systemic treatments but more advanced stage HCC was documented in the second period. An increasing number of HCC patients without liver cirrhosis were identified during the second time-period (n = 22, n= 47 respectively, p = 0.005). NASH was the most common underlying aetiology in patients without liver cirrhosis (50%), compared to alcohol use in being the primary cause in cirrhotic patients (p < 0.001). Conclusion: HCC continues to be an important health concern in our society. The number of HCC patients without liver cirrhosis is steadily increasing, with NAFLD/ NASH, due to underlying life-style diseases playing an important aetiological role. Continued efforts should be made to prevent HCC and to screen at-risk population groups. Preventative strategies and screening techniques should be adjusted in light of the changing epidemiological landscape of HCC.

Oral Intake of Inosine 5'-Monophosphate (IMP) in Mice Promotes the Absorption of Exogenous Fatty Acids and Their Conversion into Triglycerides though Enhancing the Phosphorylation of AMPK in Liver, leading To Lipohyperplasia (preprint)

Inosine 5'-monophoaphate (IMP) allows animals to sense umami. Intake of IMP in C57/KsJ-db/db (db/db) mice induced lipohyperplasia causing the liver cirrhosis, however, how to that of in normal mammals injure health is still unclear. Thus, we had investigated that intake of IMP in C57BL/6J mice effected its metabolic functions. We found that intake of 255 M/d IMP in C57BL/6J mice for 4 months induced hyperlipidemia and body fat rate raised. In mechanism, the expressions of ACC1 and phosphorylated ACC2 in hepatocytes were increased though IMP promoting phosphorylation of AMPK. The increased ACC1 promoted the conversion of acetyl-CoA into TG. These TG were transported out of hepatocytes to avoid NAFLD, causing a deficiency of acetyl-CoA in liver, and then the increased phosphorylated ACC2 promoted cytoplasm fatty acids into mitochondria to convert into acetyl-CoA though the fatty acids β-oxidation pathway, causing a deficiency of fatty acids. Therefore, liver enhanced the absorption of exogenous fatty acids, which were converted into TG caused lipohyperplasia. Moreover, intake of IMP in normal mice induced complement system weaken in liver causing mild inflammation. Our data not only alerted that humans avoid excessive intake of IMP, but also provided novel insights into the adipose of metabolic dysfunctions.

Endoscopic Submucosal Dissection for Treatment of Early-Stage Cancer or Precancerous Lesion of the Upper Gastrointestinal Tract in Patients with Liver Cirrhosis (preprint)

(1) Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the standard method for treating early-stage cancer or precancerous lesions in the upper gastrointestinal tract, however it may be difficult in patients with liver cirrhosis due to coagulation dysfunction or presence of gastroesophageal varices. We aimed to demonstrate the safety and efficacy of ESD in these population. (2) Methods: We retrospectively collected the clinical data and analyzed. Patients inclusion criteria: 1) patients with liver cirrhosis; 2) patients who underwent ESD; 3) patients diagnosed of early-stage cancer or precancerous lesions in the upper gastrointestinal tract. (3) Results: Eight patients were enrolled from April 2019 to April 2023, of whom 3 were male and 5 female, with age ranging from 43 to 70 years old. Seven lesions were located in the stomach, and the other one lesion in the esophagus. ESD was performed successfully in all patients, and the resected lesion size ranged from 2 to 6 cm. Only one patient encountered postoperative complication, chest pain and fever. No recurrence of noticed during a follow-up of 6 to 36 months. (4) Conclusions: ESD is safe and effective for treating upper gastrointestinal early-stage cancer or precancerous lesions in patients with liver cirrhosis.

Global epidemiology of cirrhosis - aetiology, trends and predictions.

Cirrhosis is an important cause of morbidity and mortality in people with chronic liver disease worldwide. In 2019, cirrhosis was associated with 2.4% of global deaths. Owing to the rising prevalence of obesity and increased alcohol consumption on the one hand, and improvements in the management of hepatitis B virus and hepatitis C virus infections on the other, the epidemiology and burden of cirrhosis are changing. In this Review, we highlight global trends in the epidemiology of cirrhosis, discuss the contributions of various aetiologies of liver disease, examine projections for the burden of cirrhosis, and suggest future directions to tackle this condition. Although viral hepatitis remains the leading cause of cirrhosis worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated cirrhosis are rising in several regions of the world. The global number of deaths from cirrhosis increased between 2012 and 2017, but age-standardized death rates (ASDRs) declined. However, the ASDR for NAFLD-associated cirrhosis increased over this period, whereas ASDRs for other aetiologies of cirrhosis declined. The number of deaths from cirrhosis is projected to increase in the next decade. For these reasons, greater efforts are required to facilitate primary prevention, early detection and treatment of liver disease, and to improve access to care.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

Multidisciplinary teams, efficient communication, procedure services, and telehealth improve cirrhosis care: A qualitative study.

BACKGROUND: Cirrhosis care and outcomes are improved with access to subspecialty gastroenterology and hepatology care. In qualitative interviews, we investigated clinicians' perceptions of factors that optimize or impede cirrhosis care. METHODS: We conducted 24 telephone interviews with subspecialty clinicians at 7 Veterans Affairs medical centers with high- and low-complexity services. Purposive sampling stratified Veterans Affairs medical centers on timely post-hospitalization follow-up, a quality measure. We asked open-ended questions about facilitators and barriers of care coordination, access to appointments, procedures, transplantation, management of complications, keeping up to date with medical knowledge, and telehealth use. RESULTS: Key themes that facilitated care were structural: multidisciplinary teams, clinical dashboards, mechanisms for appointment tracking and reminders, and local or virtual access to transplant and liver cancer specialists through the "specialty care access network extension for community health care outcomes" program. Coordination and efficient communication between transplant and non-transplant specialists and between transplant and primary care facilitated timely care. Same-day access to laboratory, procedural, and clinical services is an indicator of high-quality care. Barriers included lack of on-site procedural services, clinician turnover, patient social needs related to transportation, costs, and patient forgetfulness due to HE. Telehealth enabled lower complexity sites to obtain recommendations for complex patient cases. Barriers to telehealth included lack of credit (eg, VA billing equivalent), inadequate staff, lack of audiovisual technology support, and patient and staff discomfort with technology. Telehealth was optimal for return visits, cases where physical examination was nonessential, and where distance and transportation precluded in-person care. Rapid telehealth uptake during the COVID-19 pandemic was a positive disruptor and facilitated use. CONCLUSIONS: We identify multi-level factors related to structure, staffing, technology, and care organization to optimize cirrhosis care delivery.

Trends in aetiology-based hospitalisation for cirrhosis before and during the COVID-19 pandemic in the United States.

BACKGROUND AND AIMS: Patients with pre-existing cirrhosis and exposure to coronavirus disease-19 (COVID-19) may portend a poor prognosis. We evaluated the temporal trends in aetiology-based hospitalisations and potential predictors of in-hospital mortality in hospitalisation with cirrhosis before and during the COVID-19 pandemic. METHODS: Based on the US National Inpatient Sample 2019-2020, we determined quarterly trends in aetiology-based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in-hospital mortality in hospitalisation with cirrhosis. RESULTS: We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID-19 era. Hospitalisation rates for alcohol-related liver disease (ALD)-related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%-5.1%), with a notably higher rate during the COVID-19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)-related cirrhosis decreased steadily with a trend of -1.4% of QPC (95% CI: -2.5% to -0.1%). Quarterly trends in the proportion of ALD- (QPC: 1.7%, 95% CI: 0.9%-2.6%) and nonalcoholic fatty liver disease-related (QPC: 0.7%, 95% CI: 0.1%-1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID-19 era and COVID-19 infection were independent predictors of in-hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV-related cirrhosis, ALD-related cirrhosis was associated with a 40% higher risk of in-hospital mortality. CONCLUSION: In-hospital mortality in cirrhosis was higher in the COVID-19 era than in the pre-COVID-19 era. ALD is the leading aetiology-specific cause of in-hospital mortality in cirrhosis with an independent detrimental impact of the COVID-19 infection.

A Comparative Study of Acute Alcoholic Hepatitis vs. Non-Alcoholic Hepatitis Patients from a Cohort with Chronic Alcohol Dependence.

The rate of alcoholic hepatitis (AH) has risen in recent years. AH can cause as much as 40-50% mortality in severe cases. Successful abstinence has been the only therapy associated with long-term survival in patients with AH. Thus, it is crucial to be able to identify at-risk individuals in order to implement preventative measures. From the patient database, adult patients (age 18 and above) with AH were identified using the ICD-10 classification from November 2017 to October 2019. Liver biopsies are not routinely performed at our institution. Therefore, patients were diagnosed with AH based on clinical parameters and were divided into "probable" and "possible" AH. Logistic regression analysis was performed to determine risk factors associated with AH. A sub-analysis was performed to determine variables associated with mortality in AH patients. Among the 192 patients with alcohol dependence, there were 100 patients with AH and 92 patients without AH. The mean age was 49.3 years in the AH cohort, compared to 54.5 years in the non-AH cohort. Binge drinking (OR 2.698; 95% CI 1.079, 6.745; p = 0.03), heavy drinking (OR 3.169; 95% CI 1.348, 7.452; p = 0.01), and the presence of cirrhosis (OR 3.392; 95% CI 1.306, 8.811; p = 0.01) were identified as characteristics more commonly found in the AH cohort. Further, a higher inpatient mortality was seen in those with a probable AH diagnosis (OR 6.79; 95% CI 1.38, 44.9; p = 0.03) and hypertension (OR 6.51; 95% CI 9.49, 35.7; p = 0.02). A higher incidence of mortality was also noted among the non-Caucasian race (OR 2.72; 95% CI 4.92; 22.3; p = 0.29). A higher mortality rate despite a lower incidence of alcohol use among non-Caucasian patients may indicate healthcare disparities.

BLOOD COAGULATION DISORDERS IN PATIENTS WITH LIVER CIRRHOSIS INFECTED COVID-19.

OBJECTIVE: The aim: To investigate the features of coagulation homeostasis in patients with liver cirrhosis (LC) in COVID-19 infection. PATIENTS AND METHODS: Materials and methods: At the clinical base of the Department of Propaedeutics of Internal Medicine, 32 patients with LC infected with COVID-19 were examined - 1 Group of patients. The study also included 30 patients with LC who were not infected with COVID-19 (2 Group of patients). RESULTS: Results: The analysis of the obtained data indicates disorders of the hemostasis system in patients with LC without the COVID-19 infection (Group 2), as well as in patients with LC at the time of being infected with COVID-19. The violation of the protein synthesis function of the liver is manifested through a decrease in the level of fibrinogen in blood serum (up to 2.0±0.5 gr/l in patients of Group 1 at the time of admission for inpatient care) and up to 21.9±0.5 gr/l in patients of group ІІ - р<0.05. This was accompanied by an acceleration of prothrombin time, thrombin time and activated partial thromboplastic time in patients with LC, as well as an increase in the level of antithrombin III. The level of D-dimer was reduced both in patients of group II and in patients of group I at the time of being infected with COVID-19. CONCLUSION: Conclusions: Changes in coagulation homeostasis characteristic of hypocoagulation syndrome have been established in patients with LC. COVID-19 infection in patients with LC leads to hypercoagulation, especially in patients with complicated stage of LC (ascites, encephalopathy, hepatorenal syndrome).

Telephone-Only Visits Preserved Hepatocellular Cancer Screening Rates in Patients with Cirrhosis Early in the COVID-19 Pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic required an immediate and large-scale transition to telemedicine. Telemedicine includes phone visits and video visits. Studies suggest that hepatocellular cancer (HCC) screening rates fell at the beginning of the COVID-19 pandemic. If left unaddressed, HCC morbidity/mortality may increase following the pandemic due to inadequate screening. AIMS: To assess the impact of phone-only visits on HCC screening rates in patients with cirrhosis. METHODS: Utilizing ICD-10 codes, 2 cohorts of patients with cirrhosis were identified. The pre-pandemic cohort had index visit between 1/1/2019 and 6/30/2019 (n = 290). The pandemic cohort (n = 112) was evaluated between 4/7/2020 and 6/7/2020. Each cohort was followed for 6 months from their index visit to determine HCC screening rate. Demographics and socioeconomic data from the American Community Survey database were compiled and compared between the cohorts. RESULTS: HCC screening rates in the pre-pandemic and pandemic cohorts were 72.4% and 69.6%, respectively, p = 0.67. No differences in HCC screening rates were observed between the two cohorts when stratified by demographic and socioeconomic factors. CONCLUSIONS: Use of phone-only visits was associated with adherence to HCC screening similar to that seen with in-person visits. The lack of influence on screening rates by racial/socioeconomic factors suggest telephone-only visits do not exacerbate healthcare disparities. In times of public health of crisis, telephone-only visits may provide the necessary access to hepatology care to ensure HCC screening regimens remain in-place for at-risk patients.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.

Challenges of hepatitis B treatment in rural Sub-Saharan Africa: Treatment initiation and outcomes from a public hospital-based clinic in Kono, Sierra Leone.

Despite a high prevalence, there are few successful models for de-centralizing diagnosis and treatment of chronic hepatitis B virus (HBV) infection among rural communities in Sub-Saharan Africa. We report baseline characteristics and 1 year retention outcomes for patients enrolled in a HBV clinic integrated within chronic disease services in a rural district hospital in Sierra Leone. We conducted a retrospective cohort study of patients with HBV infection enrolled between 30 April 2019 and 30 April 2021. Patients were eligible for 1 year follow-up if enrolled before 28 February 2020. Treatment eligibility at baseline was defined as cirrhosis (diagnosed by clinical criteria of decompensated cirrhosis, ultrasonographic findings or aspartate-aminotransferase-to-platelet ratio >2) or co-infection with HIV or HCV. Retention in care was defined as a documented follow-up visit at least 1 year after enrolment. We enrolled 623 individuals in care, median age of 30 years (IQR 23-40). Of 617 patients with available data, 97 (15.7%) had cirrhosis. Treatment was indicated among 113 (18.3%) patients and initiated among 74 (65.5%). Of 39 patients eligible for 1 year follow-up on treatment at baseline, 20 (51.3%) were retained at 1 year, among whom 12 (60.0%) had documented viral suppression. Among the 232 patients not initiated on treatment eligible for 1 year follow-up, 75 (32.3%) were retained at 1 year. Although further interventions are required to improve outcomes, our findings demonstrated feasibility of retention and treatment of patients with HBV infection in a rural district in Sub-Saharan Africa, when integrated with other chronic disease services.

Viral Hepatitis and Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

Outcomes of COVID-19 among patients with liver disease.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease with multi-organ involvement, including impaired liver function. It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction, especially those with a more severe disease course. The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2, a cell-surface receptor for cellular entry, that is expressed in the liver. According to previous research, liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients, and elevated liver transaminases were found in about 20% of these patients, alkaline phosphatase in 6.1%, and gamma-glutamyl transferase in 21.1%. COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases (CLDs) and also in those without previous liver disorders. The majority of COVID-19 patients who develop liver injury are men, the elderly, and those with a higher body mass index. Compared to the general population, COVID-19 is associated with significant morbidity and mortality in patients with liver disease (cirrhosis and liver transplantation recipients). However, some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.