Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has posed a major public health concern worldwide.Patients with comorbid conditions are at risk of adverse outcomes following COVID-19.Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection.It could lead to higher rates of inpatient complications and mortality in this patient population.However,studies on COVID-19 outcomes in liver transplant(LT)recipients have yielded inconsistent findings.AIM To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.METHODS We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database.Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classi-fication of Diseases,Tenth Revision coding system.The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic.Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.RESULTS A total of 15720 hospitalized LT recipients were included.Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection.In both cohorts,the median admission age was 57 years.The linear trends for LT hospitalizations did not differ significantly before and during the pandemic(P=0.84).The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020.Compared to the pre-pandemic period,a higher association was noted between LT recipients and in-hospital mortality during the pandemic,with an odds ratio(OR)of 1.69[95% confidence interval(CI):1.55-1.84),P<0.001].The frequency of transplant rejections among hospitalized LT recipients increased from 0.2%to 3.6% between January 2019 and December 2020.LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic[OR:1.53(95%CI:1.26-1.85),P<0.001].CONCLUSION The hospitalization rates for LT recipients were comparable before and during the pandemic.Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations:A propensity-matched analysis of the United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),formally known as nonalcoholic fatty liver disease,is the most common chronic liver disease in the United States.Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019(COVID-19)and death.However,most studies are single-center studies,and nationwide data in the AIM To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic.METHODS We retrospectively analyzed the 2020 National Inpatient Sample(NIS)database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD.A matched comparison cohort of COVID-19 hospit-alizations without MASLD was identified from NIS after 1:N propensity score matching based on gender,race,and comorbidities,including hypertension,heart failure,diabetes,and cirrhosis.The primary outcomes included inpatient mortality,length of stay,and hospitalization costs.Secondary outcomes included the prevalence of systemic complications.RESULTS A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD,with a good comorbidity balance.Overall,there was a higher prevalence of severe disease with more intensive care unit admissions(9.5%vs 7.2%,P=0.007),mechanical ventilation(7.2%vs 5.7%,P=0.03),and septic shock(5.2%vs 2.7%,P<0.001)in the MASLD cohort than in the non-MASLD cohort.However,there was no difference in mortality(8.6%vs 10%,P=0.49),length of stay(5 d vs 5 d,P=0.25),and hospitalization costs(42081.5$vs 38614$,P=0.15)between the MASLD and non-MASLD cohorts.CONCLUSION The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations;however,there was an increased incidence of severe COVID-19 infection.This data(2020)predates the availability of COVID-19 vaccines,and many MASLD patients have since been vaccinated.It will be interesting to see if these trends are present in the subsequent years of the pandemic.

Hepatocellular carcinoma in non-alcoholic steatohepatitis:Current knowledge and implications for management

With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma(HCC) related to non-alcoholic steatohepatitis(NASH) is anticipated to increase exponentially due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.8%. While multiple new mechanisms have been implicated in the development of HCC in NASH; further prospective long-term studies are needed to validate these findings. Recent evidence has shown a significant proportion of patients with non-alcoholic fatty liver disease and NASH progress to HCC in the absence of cirrhosis. Liver resection and transplantation represent curative therapeutic options in select NASHrelated HCC patients but have placed a significant burden to our healthcare resources and utilization. Currently NASH-related HCC is the fastest growing indication for liver transplant in HCC candidates. Increased efforts to implement effective screening and preventative strategies, particularly in non-cirrhotic NASH patients, are needed to reduce the future impact imposed by NASH-related HCC.

Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management

Chronic hepatitis B(CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma(HCC). Liver transplantation(LT) is considered gold standard for treatment of hepatitis B virus(HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin(HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressingviral replication and improving long-term survival. The combination of lamivudine(LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA(ccc DNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.

Non-alcoholic fatty liver and chronic kidney disease:Retrospect,introspect,and prospect

With the growing prevalence of obesity and diabetes in the United States and across the world,a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease(NAFLD)is expected.The risk factors for NAFLD are also associated with the development of chronic kidney disease(CKD).We review the epidemiology,risk factors,genetics,implications of gut dysbiosis,and specific pathogenic mechanisms linking NAFLD to CKD.Mechanisms such as ectopic lipid accumulation,cellular signaling abnormalities,and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population.Transplant evaluation in the setting of both NAFLD and CKD is also reviewed.Potential strategies for surveillance and management include the monitoring of comorbidities,the use of non-invasive fibrosis scoring systems,and the measurement of laboratory markers.Lastly,we discuss the management of patients with NAFLD and CKD,from preventative measures to experimental interventions.

Liver injury in COVID-19:The hepatic aspect of the respiratory syndrome-what we know so far

The 2019 novel coronavirus disease(COVID-19)pandemic due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed a serious threat to global public health.Although primarily,the infection causes lung injury,liver enzyme abnormalities have also been reported to occur during the course of the disease.We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury.The present review summarizes available information on the spectrum of liver involvement,the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection,and the prognostic significance of the presence of liver injury.Hopefully,this review will enable clinicians,especially the hepatologists,to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19.

Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations:A ten-year United States study

BACKGROUND Chronic liver disease is associated with various neuropsychiatric conditions.There are currently no large studies assessing and comparing the prevalence of psy-chiatric illnesses based on patient profiles and the etiology of cirrhosis.AIM To examine the trends of hospitalizations among psychiatric conditions in cirrhosis.METHODS We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis.The outcomes included the prevalence,trends,and associations of psychiatric diagnoses in these hospitalizations.Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized.RESULTS The prevalence of generalized anxiety disorder(GAD)in liver cirrhosis hospitalizations increased from 0.17%in 2009 to 0.92%in 2019(P<0.001).The prevalence of depression increased from 7%in 2009 to 12%in 2019(P<0.001).Attention deficit hyperactivity disorder(ADHD)prevalence increased from 0.06%to 0.24%.The prevalence of schizophrenia increased from 0.59%to 0.87%(P<0.001).Schizoaffective disorder prevalence increased from 0.10%to 0.35%(P<0.001).Posttraumatic stress disorder(PTSD)prevalence displayed increasing trends from 0.36%in 2009 to 0.93%in 2019(P<0.001).The prevalence of suicidal ideation increased from 0.23%to 0.56%in 2019.Cirrhosis related to alcoholic liver disease[adjusted odds ratios(aOR)1.18,95%CI 1.08-1.29,P<0.001]and non-alcoholic fatty liver disease(NAFLD)(aOR 1.14,95%CI 1.01-1.28,P=0.025)was associated with depression more than other causes.Alcohol-and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders.Females had a higher association with GAD(aOR 2.56,95%CI 2.14-3.06,P<0.001),depression(aOR 1.78,95%CI 1.71-1.84,P<0.001),bipolar disorder(aOR 1.64,95%CI 1.52-1.77,P<0.001]and chronic fatigue(aOR 2.31,95%CI 1.31-4.07,P<0.001)when compared to males.Blacks,Hispanics,and Asian/Native Americans had a significantly lower association with GAD,depression,bipolar disorder,PTSD,and ADHD when compared to the white race.CONCLUSION The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade.Females had a higher association with psychiatric disorders compared to males.Blacks,Hispanics,and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients:A propensity-matched analysis from the United

BACKGROUND Alcohol-associated cirrhosis(AC)contributes to significant liver-related mortality in the United States.It is known to cause immune dysfunction and coagulation abnormalities.Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019(COVID-19).The specific association between AC and COVID-19 mortality remains inconclusive,given the lack of robust clinical evi-dence from prior studies.AIM To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States.METHODS We conducted a retrospective cohort study using the National Inpatient Sample(NIS)database 2020.Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC.A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities.Primary outcomes included median length of stay,median inpatient charges,and in-hospital mortality.Secondary outcomes included a prevalence of systemic complications.RESULTS A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC.There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC(P>0.05).There was an increased prevalence of septic shock(5.7%vs 4.1%),ventricular fibrillation/ventricular flutter(0.4%vs 0%),atrial fibrillation(13.2%vs 8.8%),atrial flutter(8.7%vs 4.4%),first-degree atrioventricular nodal block(0.8%vs 0%),upper extremity venous thromboembolism(1.5%vs 0%),and variceal bleeding(3.8%vs 0%)in the AC cohort compared to the non-AC cohort(P<0.05).There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC,with an odds ratio of 0.97(95%confidence interval:0.78-1.22,P=0.85).Predictors of mortality included advanced age,cardiac arrhythmias,coagulopathy,protein-calorie malnutrition,fluid and electrolyte disorders,septic shock,and upper extremity venous thromboembolism.CONCLUSION AC does not increase mortality in patients hospitalized with COVID-19.There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Use of direct-acting antiviral agents in hepatitis C virusinfected liver transplant candidates

Since the advent of direct acting antiviral(DAA) agents, chronic hepatitis C virus(HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant(LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response(SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

Presentation, patterns and predictive value of baseline liver tests on outcomes in COVID-19 patients without chronic liver disease

BACKGROUND Coronavirus disease 2019(COVID-19)infection is known to cause abnormal hepatic enzymes.The long term consequences of such elevations are uncertain.AIM To assessed the prevalence and prognostic value of initial liver enzymes in a large cohort of COVID-19 patients.METHODS We reviewed electronic medical records of 10614 COVID-19 patients without known chronic liver disease who were admitted to our health system from March 1,2020,to April 30,2020.We analyzed baseline demographics and liver chemistries.The primary outcome was in-hospital mortality,and the secondary outcome was a composite of in-hospital mortality or need for mechanical ventilation.RESULTS Subjects with abnormal liver tests had increased risks of mortality and composite outcome when compared to patients with normal measurements on unadjusted analysis and after adjustment for demographic factors.CONCLUSION In our diverse patient population,liver enzyme abnormalities are associated with increased mortality and the need for mechanical ventilation in subjects without chronic liver disease.Cholestasis patients are at the greatest risk for poor outcomes.

Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence

The coronavirus disease 2019(COVID-19)pandemic has swept through nations,crippled economies and caused millions of deaths worldwide.Many people diagnosed with COVID-19 infections are often found to develop liver injury,which,in a small portion of patients,progresses to severe liver disease.Liver injury in the form of elevated transaminases,hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease.Those who already have insult to the liver from chronic disease,such as nonalcoholic fatty liver disease(NAFLD)may be at the greatest disadvantage.The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities.About 25%of the global population has NAFLD.With such a widespread prevalence of NAFLD,understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance.In this review,we present an overview of COVID-19 infection in patients with NAFLD.

NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States

Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney trans-plantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggres-sive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Re-current nonalcoholic steatohepatitis after LT is not uncom-mon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.