Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Association of metabolic dysfunction-associated fatty liver disease with gastrointestinal infections: insights from National Inpatient Sample Database.

OBJECTIVES: The study aimed to compare the risk of gastrointestinal infections among patients with and without metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This was a population-based, retrospective, observational study using data from the National Inpatient Sample (NIS), the largest all-payer US inpatient care database. SETTING: Hospitalisation of adults aged ≥18 years old admitted in 2020 was identified using the NIS. Patients were stratified by the presence and absence of MAFLD. PARTICIPANTS: 26.4 million adults aged ≥18 years old were included in the study. Patients younger than 18 and those with missing demographic or mortality data were excluded. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was to assess the overall risk of gastrointestinal infections in patients with and without MAFLD. Secondary outcomes were demographics and comorbidities stratified by the presence or absence of gastrointestinal infection, and the risk of specific gastrointestinal pathogens. RESULTS: Of 26.4 million patients admitted in 2020, 755 910 (2.85%) had the presence of MAFLD. There was a higher prevalence of bacterial gastrointestinal infections in patients with MAFLD than those without (1.6% vs 0.9%, p<0.001). The incidence of Clostridioides difficile (1.3% vs 0.8%, p<0.001), Escherichia coli (0.3% vs 0.01%, p<0.001), and Salmonella (0.07% vs 0.03%, p<0.001) was higher in patients with MAFLD. The presence of MAFLD was associated with higher odds of developing gastrointestinal infections (adjusted OR (aOR) -1.75, 95% CI -1.68 to 1.83, p<0.001). After adjusting for confounders, results remained statistically significant (aOR -1.36, 95% CI - 1.30-1.42, p<0.001). CONCLUSION: Even after adjusting for confounding factors, our study demonstrates an increased risk of gastrointestinal infections in patients with MAFLD, specifically of C. difficile, E. coli, and Salmonella. The immune and microbiota changes seen within MAFLD potentially contribute to the increased risk of gastrointestinal infections.

Recent Trends in Palliative Care Utilization in Patients With Decompensated Liver Disease: 2016-2020 National Analysis.

Background: Patients with end-stage liver disease (ESLD) have a poor quality of life, which often worsens as disease severity increases. Palliative care (PC) has emerged as a management option in ESLD patients, especially for those who are not candidates for a liver transplant. Objective: To assess the associated factors and trends in PC utilization in recent years. Design: We used the 2016-2020 National Inpatient Sample (NIS) database of the United States to identify patients with decompensated cirrhosis who suffered in-hospital mortality. Information regarding patient demographics, hospital characteristics, etiology and decompensations, Elixhauser comorbidities, and interventions was collected. The multivariate regression model was used to identify factors associated with PC use. Results: Out of 98,160 patients, 52,645 patients (53.6%) received PC consultations. PC utilization increased from 49.11% in 2016 to 56.85% in 2019, with a slight decrease to 54.47% in 2020. Patients with PC use had decreased incidence of blood transfusions (28.85% vs. 36.53%, p < 0.001), endoscopy (18% vs. 20.26%, p 0.0001), liver transplantation (0.28% vs. 0.69%, p < 0.001), and mechanical ventilation (46.22% vs. 56.37%, p < 0.001). African American, Hispanic, and Asian/Pacific Islander patients had 29%, 27%, and 23% lower odds of receiving PC than White patients. Patients in the two lowest income quartiles had 12% and 22% lower odds of receiving PC compared with the highest quartile. Conclusions: PC utilization in patients with ESLD is associated with decreased invasive procedures, shorter lengths of stay, and lower hospitalization charges. Minorities, as well as patients in the lower income quartiles, were less likely to receive PC.

Vaccine-Preventable Illness Leads to Adverse Outcomes in Liver Transplant Recipients.

BACKGROUND: Liver transplant recipients (LTR) and patients with chronic liver disease (CLD) are at an increased risk of infections. AIMS: The objective of our study was to assess the incidence, and impact of vaccine preventable illness (VPI) on outcomes in LTR. METHODS: National Inpatient Sample (NIS) 2016-2020 was used to identify adults (age > 18) hospitalized LTR using ICD-10 codes. Data were collected on patient demographics, hospital characteristics, etiology of liver disease, hepatic decompensations and outcomes. Patients were stratified into two groups based on the presence or absence of VPI. Multivariate logistic regression analysis was performed to identify the association between VPI and outcomes. RESULTS: Out of 170,650 hospitalized LTR, 13.5% of the patients had VPI. The most common VPI was noted to be influenza (10.7%), followed by pneumococcal infection (2.7%). Incidence of mortality (6.9% vs. 1.6%, p < 0.001), ICU admissions (14.3% vs. 3.4%, p < 0.001), and acute kidney injury (AKI) (43.7% vs 37.35%, p < 0.001) was higher in the VPI group. CONCLUSION: More than 13% of the LT hospitalizations had concomitant VPI. VPI in LTR was associated with worse outcomes. Our data suggests the need to identify factors associated with reduced vaccination rates and identify strategies to improve vaccination rates and responses in these patients.

FIB-4 Reliability in Patients With Severe Obesity: Lower Cutoffs Needed?

BACKGROUND: Liver biopsy is the gold standard to evaluate hepatic fibrosis; however, it has many drawbacks, especially in patients with severe obesity. Noninvasive testing such as the FIB-4 score is increasingly being used as the initial screening tool to identify patients at risk for advanced fibrosis. The broader applicability of FIB-4 and the precision of its cutoff values remain uncertain in metabolic dysfunction-associated steatotic liver disease and patients with severe obesity. Our study explored the correlation between FIB-4 scores and intraoperative liver biopsy in patients with severe obesity undergoing bariatric surgery. METHODS: A total of 632 patients with severe obesity underwent preoperative vibration-controlled transient elastography and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, vibration-controlled transient elastography, and liver biopsy results. ANOVA 1-way test, χ2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The proposed FIB-4 cutoffs for F0-1, F2, F3, and F4 were 0.62 (CI: 0.59, 0.64), 0.88 (0.74, 1.01), 1.24 (0.94, 1.54), and 1.53 (0.82, 2.24), respectively. Area under the curve (AUC) methods were used to compare traditional to proposed cutoff values. RESULTS: Applying the traditional FIB-4 cutoffs to approximate advanced fibrosis yielded an AUC of 0.5748. Use of the proposed FIB-4 cutoffs increased the AUC to 0.6899. The proposed FIB-4 cutoffs correctly identified 40 patients with biopsy-proven advanced fibrosis (F3-F4), all of which would have been missed using traditional cutoffs. CONCLUSION: Our study revealed that the use of the currently accepted FIB-4 cutoffs as the screening modality for identifying patients with advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease is insufficient and will result in missing patients with histologically confirmed advanced fibrosis. Use of the revised FIB-4 scores should be considered to diagnose patients with severe obesity at high risk of liver disease progression.

Unusual sites of hepatocellular carcinoma metastasis: Case report.

Hepatocellular carcinoma is an increasingly frequent cause of cancer-related death. The majority of patients with hepatocellular carcinoma are asymptomatic. In rare cases, patients may present with symptoms of extrahepatic metastases. Early identification can lead to timely treatment and prevent poor outcomes. We report three cases of patients with hepatocellular carcinoma with unusual sites of metastasis, including clival, mandible, and cardiac involvement.

Frailty as a risk-stratification tool in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS).

Objectives: The concept of frailty has gained importance, especially in patients with liver disease. Our study systematically investigated the effect of frailty on post-procedural outcomes in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). Methods: We used National Inpatient Sample(NIS) 2016-2019 data to identify patients who underwent TIPS. Hospital frailty risk score (HFRS) was used to classify patients as frail (HFRS>=5) and non-frail (HFRS<5). The relationship between frailty and outcomes such as death, post-procedural shock, non-home discharge, length of stay (LOS), post-procedural LOS, and total hospitalization charges (THC) was assessed. Results: A total of 13,700 patients underwent TIPS during 2016-2019. Of them, 5,995 (43.76%) patients were frail, while 7,705 (56.24%) were non-frail. There were no significant differences between the two groups based on age, gender, race, insurance, and income. Frail patients had higher mortality (15.18% vs. 2.07%, p<0.001), a higher incidence of non-home discharge (53.38% vs. 19.08%, p<0.001), a longer overall LOS (12.5 days vs. 3.35,p<0.001), longer post-procedural stay (8.2 days vs. 3.4 days, p<0.001), and higher THC ($240,746.7 vs. $121,763.1, p<0.001) compared to the non-frail patients. On multivariate analysis, frail patients had a statistically significant higher risk of mortality (aOR-3.22, 95% CI-1.98- 5.00, p<0.001). Conclusion: Frailty assessment can be beneficial in risk stratification in patients undergoing TIPS.

Impact of COVID-19 pandemic on alcohol-related hepatitis admissions: Analysis of nationwide data 2016-2020.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic was a public health crisis affecting medical, social, and psychological wellness. In a previous study, we reported a rise in alcohol-related hepatitis (ARH) cases between 2019 and 2020 in the central valley of California. Our goal in the current study was to assess the impact of COVID-19 on ARH at a national level. MATERIALS AND METHODS: We used data from the 2016 to 2020 National Inpatient Sample. All adult patients diagnosed with ARH (ICD10 K70.1 and K70.4) were included. Information was collected regarding patient demographics, hospital characteristics, and severity of hospitalization. We analyzed the annual percentage changes (PC) between 2016-2019 and 2019-2020 to assess the impact of COVID-19 on hospitalizations. Multivariate logistic regression analysis was performed to identify factors associated with increased ARH admissions between 2016 and 2020. RESULTS: A total of 823,145 patients were admitted with ARH. The total number of cases increased from 146,370 in 2016 to 168,970 in 2019 (annual percentage change (PC) 5.1%), while the cases increased to 190,770 in 2020 (PC 12.4%). The PC in women was 6.6% between 2016 and 2019, which increased to 14.2% between 2019 and 2020. In men, PC increased by 4.4% between 2016 and 2019 to 12.2% between 2019 and 2020. On multivariate analysis, after adjusting for patient demographics and hospital characteristics, there was 46% increased odds of admission with ARH in 2020, compared to 2016. The total number of deaths increased from 8725 in 2016 to 9190 in 2019 (PC 1.7%), while the total number of deaths increased to 11,455 in 2020 (PC 24.6%). CONCLUSIONS: A sharp rise in the cases of ARH between 2019 and 2020 was noted, which aligned with the COVID-19 pandemic. Not only did total hospitalization increase, but an increase in mortality was also noted, reflecting higher severity in the patients admitted during the COVID-19 pandemic.

Alcohol-related hepatitis: A review article.

Alcohol-related hepatitis (ARH) is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by significant alcohol use. It ranges in severity from mild to severe and carries significant morbidity and mortality. The refinement of scoring systems has enhanced prognostication and guidance of clinical decision-making in the treatment of this complex disease. Although treatment focuses on supportive care, steroids have shown benefit in select circumstances. There has been a recent interest in this disease process, as coronavirus disease 2019 pandemic led to substantial rise in cases. Although much is known regarding the pathogenesis, prognosis remains grim due to limited treatment options. This article summarizes the epidemiology, genetics, pathogenesis, diagnosis and treatment of ARH.

A Complex Diagnosis of Ampullary Adenocarcinoma Presenting As Decompensated Cirrhosis.

Neoplasms arising from the ampulla of Vater are exceedingly rare, and there is a paucity of literature regarding their diagnosis and management. Ampullary cancer typically presents with jaundice and signs of biliary obstruction. We present a case of ampullary adenocarcinoma with concomitant choledocholithiasis that proved complex and diagnostically challenging.

Refractory gastric ulcer bleeding responsive to long-term octreotide.

Upper gastrointestinal tract bleeding is a common condition that can cause hemodynamic instability and death if left untreated. Endoscopic hemostasis is often successful; however, some patients may develop refractory bleeding. Pharmacologic management with octreotide is beneficial in patients with variceal bleeding and has been shown in some studies to be effective in refractory bleeding due to angiodysplasia. There is a paucity of literature regarding the usage of long-term octreotide in refractory bleeding secondary to a peptic ulcer. We present a case of a bleeding gastric ulcer that was refractory to endoscopic management but responsive to long-term octreotide therapy.

Development of Liver Cancers as an Unexpected Consequence of Anabolic Androgenic Steroid Use.

Although the relationship between androgens and hepatocellular tumor development has been noted since 1975, cases involving hepatocellular carcinoma (HCC) or cholangiocarcinoma development in patients on chronic androgen therapy or anabolic androgenic steroid (AAS) use are few, and far between. We present three cases of patients who developed hepatic and bile duct malignancies in the setting of AAS use and testosterone supplementation, arising from a single tertiary referral center. Additionally, we review the literature for the mechanisms behind the possible androgen-mediated malignant transformation of these liver and bile duct tumors.

Soaring rates of alcohol-related hepatitis in the latter phase of the COVID-19 pandemic: A new normal?

Background: Studies have reported that the COVID-19 pandemic has led to an increase in alcohol consumption and alcohol-associated health problems in the general population. Our previous study documented a rise in severe alcohol-related hepatitis cases requiring inpatient admission in our hospital system in the early pandemic (2019 vs. 2020). This study assesses the rates of severe alcohol-related hepatitis in the latter part of the pandemic (2021). Methods: We performed a retrospective chart review via an electronic medical record to evaluate the number of cases of alcohol-related hepatitis in patients presenting to three community hospitals in Fresno, California, between 2019 (pre-pandemic) and 2021. A total of 547 patients were included in the study. We compared the demographics, clinical course, and outcomes of patients with alcohol-related hepatitis pre-pandemic (2019), early pandemic (2020), and during the later phase of the pandemic (2021). Results: The number of cases increased from 131 in 2019 to 201 in 2020 and 215 in 2021 (53% and 64% increase, respectively). The number of young patients (age <40 years) increased from 30 in 2019 to 61 in 2020 and 71 in 2021 (103% and 136% increase, respectively) (p = 0.13). The number of admissions of women increased from 24 in 2019 to 55 in 2020 and 67 in 2021 (129% and 179% increase, respectively) (p = 0.026). Deaths during hospitalization increased from 20 in 2019 to 26 in 2021 (p = 0.674). The number of rehospitalizations within 3 months increased 4.5 times from 18 in 2019 to 80 in 2021 (p < 0.001). Conclusion: Our study revealed that the admissions for alcohol-related hepatitis remained significantly above the pre-pandemic levels through the end of 2021. We believe this sustained increase in cases of alcohol-related hepatitis in our hospital system reflects a much larger national problem. Alcohol-related hepatitis is associated with significant morbidity, mortality, and societal cost. Urgent public health interventions are needed at a national level to prevent this rise in cases from becoming a new normal.

A tough pill to swallow: Two cases of statin-induced necrotizing autoimmune myopathy manifesting as dysphagia and transaminitis.

Although 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors are well tolerated, a small subset of patients may develop autoimmune myopathy, classified as immune-mediated necrotizing myopathy. Statin-induced immune-mediated necrotizing myopathy can present as proximal muscle weakness and in some cases as dysphagia and respiratory distress. We present two cases of patients taking statins who developed dysphagia and muscle weakness found to have statin-induced immune-mediated necrotizing myopathy. Both patients were treated with immunosuppressive therapy: one did well clinically, while the other had an aggressive form of statin-induced immune-mediated necrotizing myopathy and succumbed to the disease. Although statin-induced immune-mediated necrotizing myopathy is rare, early treatment to induce remission of this disabling condition should be initiated to prevent morbidity and mortality.

Long-term clinical outcomes of patients with COVID-19 and chronic liver disease: US multicenter COLD study.

BACKGROUND: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited. METHODS: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19. RESULTS: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31-462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n=1332), patients with CLD with COVID-19 had worse long-term survival [p<0.001; hazards ratio (HR): 1.69; 95% CI: 1.19-2.41] and higher rate of hospitalization (p<0.001, HR: 2.00, 1.62-2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p=0.05, HR: 2.45, 1.01-2.11), Hispanic ethnicity (p=0.003, HR: 1.94, 1.26-2.99), and severe COVID-19 requiring mechanical ventilation (p=0.028, HR: 1.74, 1.06-2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n=470) of patients with CLD and history of COVID-19, of whom, 70% (n=326) had received the COVID-19 vaccine. CONCLUSIONS: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems.

Iron Man: Non-HFE Hemochromatosis Without Significant Fibrosis.

Hemochromatosis is a genetic disorder marked by abnormally high levels of intestinal iron absorption leading to severe end-organ damage. It is classically associated with HFE gene mutations, including C282Y and H63D, but in recent years, many non-HFE mutations along with novel variants have been discovered, particularly among non-Whites. We describe a case of an elderly Japanese patient who was evaluated for markedly elevated ferritin found to have hemochromatosis, with no hepatic fibrosis while being negative for HFE and common non-HFE gene mutations.

Hepatitis E infection: A review.

Hepatitis E virus (HEV) is a small non-enveloped virus that is transmitted via the fecal-oral route. It is a highly common cause of acute hepatitis, particularly in low to middle income regions of Asia, Africa, and Central America. Most cases are self-limited, and symptomatic patients usually present with acute icteric hepatitis. A subset of patients including pregnant women, older men, those with pre-existing liver disease and immunocompromised patients however, may develop severe disease and hepatic failure. Immunocompromised patients are also at risk for chronic infection, and their immunosuppression should be decreased in order to facilitate viral clearance. HEV can also present with a variety of extra-intestinal manifestations including neurological, renal, hematological, and pancreatic derangements. The gold standard of diagnosis is HEV ribonucleic acid detection via nucleic acid amplification testing. Currently, there are no approved treatments for Hepatitis E, though ribavirin is the most commonly used agent to reduce viral load. Studies assessing the safety and efficacy of other antiviral agents for HEV are currently underway. HEV vaccination has been approved in China, and is currently being investigated in other regions as well. This review article aims to discuss the epidemiology, pathogenesis, presentation, diagnosis, complications, and treatment of Hepatitis E infection.

Predictors of leaving against medical advice in patients with alcohol-related hepatitis.

Background: Alcohol-related hepatitis is one of the most severe manifestations of alcohol-related liver disease and has been associated with significant morbidity, mortality and financial burden. Patients with alcohol use disorders are at risk of leaving against medical advice (LAMA); however, there is currently a lack of data in the literature to show which patients are at higher risk. In this study, we investigated the specific demographic factors and comorbidities associated with LAMA. Methods: Patients with a primary or secondary discharge diagnosis of alcohol-related hepatitis (ICD10-CM codes K70.4 and K70.1) between January 2016 and December 2019 were included in this study. Demographics, comorbidities, complications and interventions were studied in for patients who LAMA. Multivariate analysis was conducted to elucidate factors contributing to the increased risk of alcohol-related hepatitis. Results: A total of 538,750 patients were admitted with a diagnosis of alcohol-related hepatitis. Of these, 31,500 (5.84%) patients LAMA. Older age, Hispanic race, private insurance, and higher income status were associated with a lower risk of LAMA, while younger age, African American race, lack of insurance and being in the lowest income quartile were associated with the highest risk. Conclusions: Our findings demonstrated that significant differences exist between patients with alcohol-related hepatitis who LAMA and those who remain hospitalized until discharge. We believe that this study will help healthcare providers identify patients at risk of LAMA, and help promote the targeted education of specific subgroups to improve their understanding of their disease state and decrease adverse events.

Role of endoscopic evaluation prior to diagnostic transesophageal echocardiography: Is it necessary?

Background and Aim: Esophagogastroduodenoscopy (EGD) is often performed prior to transesophageal echocardiogram (TEE) to evaluate for esophageal pathologies. Although TEE is a safe procedure, some contraindications exist, such as esophageal varices. The incidence of bleeding with TEE is <0.01%, which questions the need for this routine invasive procedure prior to TEE. We sought to characterize patients in whom pre-TEE endoscopy was requested to determine its clinical utility and identify those that would most benefit. Methods: We retrospectively studied patients who underwent EGD for TEE clearance between January 2014 and October 2019. We assessed how often EGD changed management and complications after TEE in those with EGD abnormalities. Results: Eighty-three patients were included. Twenty-three percent had prior GI bleed, 63% had cirrhosis, 18% had known varices, and 7% had prior variceal bleed. The most common EGD findings were varices (33%). Eighty-one percent proceeded with TEE. Reasons for TEE deferral included varices (12.5%), high-risk bleeding lesion (12.5%), and mechanical abnormality (12.5%). In the majority (37.5%), TEE was deemed no longer indicated. No patient undergoing TEE had significant hemoglobin drop or overt bleeding. The most common reason for not performing TEE was unrelated to EGD findings: lack of ongoing indication for TEE. Conclusion: Based on our study, EGD is likely not needed for TEE clearance in patients with varices or prior GI bleed. Given that data are limited in patients with abnormalities such as strictures, EGD may still be warranted for these patients. Further studies to identify which patients will benefit from pre-TEE endoscopy are warranted.