Prevalence of steatotic liver disease, MASLD, MetALD and significant fibrosis in people with HIV in the United States.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD. AIMS: To assess the effects of this new nomenclature on the prevalence and distribution of different SLD categories in people with HIV (PWH) and identified factors associated with MASLD and clinically significant fibrosis (CSF). METHODS: PWH were prospectively enrolled from 9 US centres and underwent clinical evaluation and vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SLD was defined as CAP ≥ 263 dB/m, CSF as LSM of ≥8 kPa, and advanced fibrosis (AF) as LSM ≥ 12 kPa. The prevalence of SLD, MASLD, metabolic dysfunction and alcohol-associated liver disease (MetALD), ALD, cryptogenic (cSLD), CSF and AF were determined. Uni- and multivariate logistic regression models were used to assess factors associated with MASLD and CSF risk. RESULTS: Of 1065 participants, 74% were male, mean (SD) age 51.6 ± 11.9 years, 46% non-Hispanic Black and 74% with undetectable HIV RNA. The prevalence of SLD was 52%, MASLD 39%, MetALD 10%, ALD 3%, CSF 15% and AF 4%. Only 0.6% had cSLD. Black race was protective whereas obesity, ALT and AST levels were associated with increased risk of MASLD and CSF in MASLD. HIV or antiretroviral therapy did not affect MASLD risk. CONCLUSIONS: MASLD and MetALD are the dominant causes of SLD in PWH, affecting almost half. Application of the new nomenclature resulted in minimal change in the proportion of patients with MASLD who would have been diagnosed previously with NAFLD.

Trends in the Prevalence of Hepatitis C Infection During Pregnancy and Maternal-Infant Outcomes in the US, 1998 to 2018.

Importance: Injection drug use is the primary risk factor for hepatitis C virus (HCV) infection in adults. More than one-third of newly reported HCV cases occur in women, particularly among persons aged 20 to 39 years. However, nationally representative data on HCV during pregnancy are limited. Objective: To estimate the temporal trend of HCV-positive pregnancies during the opioid epidemic and identify HCV-associated maternal and perinatal outcomes. Design, Setting, and Participants: A cross-sectional study was performed with data from the US, from calendar year 1998 through 2018. Data analysis was conducted from November 14, 2021, to May 14, 2023. Participants included women during in-hospital childbirth or spontaneous abortion in the National Inpatient Sample of the Healthcare Cost and Utilization Project. Exposure: Maternal HCV infection. Main Outcomes and Measures: The main outcome was the temporal trend, measured as change in the annual prevalence, in the prevalence of HCV positivity among pregnant women since the start of the opioid epidemic in the late 1990s. Secondary outcomes were the associations shown as relative odds between maternal HCV infection and maternal and perinatal adverse events. Results: During the study period, more than 70 million hospital admissions resulted in childbirth or spontaneous abortion. Among them, 137 259 (0.20%; 95% CI, 0.19%-0.21%) involved mothers with HCV; these individuals were more often White (77.4%; 95% CI, 76.1%-78.6%), low-income (40.0%; 95% CI, 38.6%-41.5%), and likely to have histories of tobacco (41.7%; 95% CI, 40.6%-42.9%), alcohol (1.8%; 95% CI, 1.6%-2.0%), and opioid (28.9%; 95% CI, 27.3%-30.6%) use compared with HCV-negative mothers. The median age of women with HCV was 28.0 (IQR, 24.3-32.2) years, and the median age of HCV-negative women was 27.2 (IQR, 22.7-31.8) years. The prevalence of HCV-positive pregnancies increased 16-fold during the study period, reaching 5.3 (95% CI, 4.9-5.7) cases per 1000 pregnancies in 2018. Age-specific prevalence increases ranged from 3-fold (age, 41-50 years) to 31-fold (age, 21-30 years). Higher odds of cesarean delivery, preterm labor, poor fetal growth, or fetal distress were associated with HCV-positivity during pregnancy. However, no significant differences were observed in gestational diabetes, preeclampsia, eclampsia, or stillbirths. Conclusions and Relevance: In this cross-sectional study, the prevalence of HCV-positive pregnancies increased markedly, and maternal HCV infection was associated with increased risks for adverse perinatal outcomes. These data may support recent recommendations for universal HCV screening with each pregnancy.

Cardiovascular Outcomes and Mortality After Bariatric Surgery in Patients With Nonalcoholic Fatty Liver Disease and Obesity.

Importance: Bariatric surgery (BS) is associated with significantly reduced incidence of cardiovascular diseases and mortality in patients with obesity. However, whether BS can decrease major adverse cardiovascular events in patients with nonalcoholic fatty liver disease (NAFLD) remains poorly understood. Objective: To investigate the association of BS with the incidence of adverse cardiovascular events and all-cause mortality in patients with NAFLD and obesity. Design, Setting, and Participants: This was a large, population-based, retrospective cohort using data from the TriNetX platform. Adult patients with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 35 or greater and NAFLD (without cirrhosis) who underwent BS between January 1, 2005, and December 31, 2021, were included. Patients in the BS group were matched with patients who did not undergo surgery (non-BS group) according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. Patient follow-up ended on August 31, 2022, and data were analyzed in September 2022. Exposures: Bariatric surgery vs nonsurgical care. Main Outcomes and Measures: The primary outcomes were defined as the first incidence of new-onset heart failure (HF), composite cardiovascular events (unstable angina, myocardial infarction, or revascularization, including percutaneous coronary intervention or coronary artery bypass graft), composite cerebrovascular disease (ischemic or hemorrhagic stroke, cerebral infarction, transient ischemic attack, carotid intervention, or surgery), and a composite of coronary artery procedures or surgeries (coronary stenting, percutaneous coronary intervention, or coronary artery bypass). Cox proportional hazards models were used to estimate hazard ratios (HRs). Results: Of 152 394 eligible adults, 4693 individuals underwent BS; 4687 patients who underwent BS (mean [SD] age, 44.8 [11.6] years; 3822 [81.5%] female) were matched with 4687 individuals (mean [SD] age, 44.7 [13.2] years; 3883 [82.8%] years) who did not undergo BS. The BS group had significantly lower risk of new-onset of HF (HR, 0.60; 95% CI, 0.51-0.70), cardiovascular events (HR, 0.53; 95% CI, 0.44-0.65), cerebrovascular events (HR, 0.59; 95% CI, 0.51-0.69), and coronary artery interventions (HR, 0.47; 95% CI, 0.35-0.63) compared with the non-BS group. Similarly, all-cause mortality was substantially lower in the BS group (HR, 0.56; 95% CI, 0.42-0.74). These outcomes were consistent at follow-up duration of 1, 3, 5, and 7 years. Conclusions and Relevance: These findings suggest that BS was significantly associated with lower risk of major adverse cardiovascular events and all-cause mortality in patients with NAFLD and obesity.

Impact of nonalcoholic fatty liver disease on clinical outcomes in patients with COVID-19 among persons living with HIV: A multicenter research network study.

BACKGROUND: People living with human immunodeficiency virus (PLWH) are at an increased risk of nonalcoholic fatty liver disease (NAFLD) but how these patients react to COVID-19 infection is unclear. We examined the clinical characteristics and outcomes of patients with and without nonalcoholic fatty liver disease (NAFLD) among people living with human immunodeficiency virus (PLWH) diagnosed with COVID-19. METHODS: A multicenter, retrospective cohort study was conducted using TriNetX. Participants diagnosed with COVID-19 between January 20, 2020, and October 31, 2021, in PLWH were identified and divided into cohorts based on preexisting NAFLD. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization, severe disease, critical care, need for mechanical ventilation, and acute kidney injury(AKI). Propensity score matching (PSM) mitigated the imbalance among group covariates. Risk ratios (RR) with 95 % confidence intervals (CI) were calculated. RESULTS: Of the 5012 PLWH identified with confirmed COVID-19 during the study period, 563 had a diagnosis of NAFLD. After PSM, both groups were well-matched with 561 patients. The primary outcome did not differ between the cohorts at 30-days, even after a fully adjusted analysis, and the risk of all-cause mortality did not differ at 60 and 90 days. NAFLD had a significantly higher risk for hospitalization rates (RR 1.32; 95 % CI, 1.06-1.63) and AKI (RR 2.55; 95 % CI 1.42-4.57) than the non-NAFLD group at 30 days. No other differences were detected in other secondary outcome measures. CONCLUSIONS: Preexisting NAFLD is associated with an increased risk for hospitalization and AKI among PLWH infected with COVID-19. The potential role of NAFLD in developing severe COVID-19 among PLWH remains to be elucidated in future studies. Still, this study indicates the need for careful monitoring of this at-risk population.

Risk of adverse cardiovascular outcomes among people with HIV and nonalcoholic fatty liver disease.

OBJECTIVE: To examine and compare the risk of major adverse cardiovascular events (MACEs) between people with HIV (PWH) with and without nonalcoholic fatty liver disease (NAFLD). DESIGN: Population-based, multicenter, retrospective cohort study. METHODS: Data on PWH between January 1, 2008, and December 31, 2020 were extracted from the TriNetX database. Primary outcomes were defined as the first incidence of myocardial infarction (MI), MACE, new-onset heart failure (HF), and a composite of cerebrovascular disease. Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 151 868 patients were identified as having HIV. After exclusions, 4969 patients were identified as having NAFLD. Of them, 4463 (90%) were propensity matched to a non-NAFLD control. Patients with NAFLD were older (42.9 versus 40.8 years). Among the NAFLD cohort, most participants were male and had a smoking history (12.3 versus 9.8%) than non-NAFLD. The mean follow-up was 4.8 ±â€Š1.1 years for the NAFLD group and 5.3 ±â€Š1.2 years for the non-NAFLD group. The risk of all outcomes was statistically significantly higher in NAFLD patients compared to those without NAFLD: MI (HR, 1.49; 95% CI, 1.11-2.01) MACE (HR, 1.49; 95% CI, 1.25-1.79), HF (HR, 1.73; 95% CI 1.37-2.19) and, cerebrovascular diseases (HR, 1.25; 95% CI, 1.05-1.48) and sensitivity analysis showed similar magnitude to the one generated in the primary analysis. CONCLUSIONS: Patients with NAFLD have an elevated risk of adverse cardiovascular events (CVEs). The results indicate the need for targeted efforts to improve awareness of risks factors associated with adverse CVEs risk in PWH with NAFLD.

It Can't Be a Coincidence: A Comparison of Cases of Autoimmune Hepatitis After Vaccination Against COVID-19.

While rare, there is now a documented cohort of patients presenting with autoimmune hepatitis secondary to vaccination against COVID-19. With this case report, we aim to compare the published cases in order to discern any unifying characteristics among those affected, and share the story of a seventy-two-year old patient presenting with autoimmune hepatitis less than two weeks after receiving his first dose of the Pfizer COVID-19 vaccine.

Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis: A population-based matched cohort study.

BACKGROUND: Patients with autoimmune hepatitis (AIH) require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019 (COVID-19) outcomes. There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases. AIM: To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive adult patients (≥ 18 years) diagnosed with COVID-19 using the TriNeTx research network platform. The outcomes of patients with AIH (main group) were compared to a propensity score-matched cohort of patients: (1) Without chronic liver disease (CLD); and (2) Patients with CLD except AIH (non-AIH CLD) control groups. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization rate, need for critical care, severe disease, mechanical ventilation, and acute kidney injury (AKI). For each outcome, the risk ratio (RR) and confidence intervals (CI) were calculated to compare the association of AIH with the outcome. RESULTS: We identified 375 patients with AIH, 1647915 patients with non-CLD, and 15790 patients with non-AIH CLD with COVID-19 infection. Compared to non-CLD patients, the AIH cohort had an increased risk of all-cause mortality (RR = 2.22; 95%CI: 1.07-4.61), hospitalization rate (RR = 1.78; 95%CI: 1.17-2.69), and severe disease (RR = 1.98; 95%CI: 1.19-3.26). The AIH cohort had a lower risk of hospitalization rate (RR = 0.72; 95%CI: 0.56-0.92), critical care (RR = 0.50; 95%CI: 0.32-0.79), and AKI (RR = 0.56; 95%CI: 0.35-0.88) compared to the non-AIH CLD patients. CONCLUSION: Patients with AIH are associated with increased hospitalization risk, severe disease, and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of COVID-19. However, patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD.

MELD or MELD-Na as a Predictive Model for Mortality Following Transjugular Intrahepatic Portosystemic Shunt Placement.

Background and Aim: The model for end-stage liver disease (MELD) was originally developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS). The MELD-sodium (MELD-Na) score has replaced MELD for organ allocation for liver transplantation. However, there are limited studies to compare the MELD with MELD-Na to predict mortality after TIPS. Methods: We performed a retrospective chart review of patients who underwent TIPS placement between 2006 and 2016 at our institution. The primary outcome was mortality, and the secondary outcomes sought to assess which variables could provide prognostic information for mortality after TIPS placement. We performed receiver operating characteristic (ROC) curve analysis to assess the performance of MELD and MELD-Na. Results: There were 186 eligible patients in the analysis. The mean pre-TIPS MELD and MELD-Na were 13 and 15, respectively. Overall, mortality after TIPS was 15% at 30 days and 16.7% at 90 days. In a comparison of the areas under the ROCs for MELD and MELD-Na, MELD was superior to MELD-Na for 30-day (0.762 vs. 0.709) and 90-day (0.780 vs. 0.730) mortality after TIPS. The optimal cutoff score for 30-day mortality was 15 (0.676-0.848) for MELD and 17 (0.610-0.808) for MELD-Na, whereas the optimal cutoff score for 90-day mortality was 16 (95% CI: 0.705-0.855) for MELD and 17 (95% CI: 0.643-0.817) for MELD-Na. There were 24 patients with high MELD-Na ≥17, but with low MELD <15, and 90-day mortality in this group was 8.3%. Conclusions: Although MELD-Na is a superior prognostic tool to MELD for predicting overall mortality in cirrhotic patients, MELD tended to outperform MELD-Na to predict mortality after TIPS.

Risk of Severe Illness and Risk Factors of Outcomes of COVID-19 in Hospitalized Patients with Chronic Liver Disease in a Major U. S. Hospital Network.

Methods: We studied 2731 patients with known CLD who were hospitalized at the Johns Hopkins Health System with COVID-19 between March 1, 2020, and December 15, 2021. The primary outcome was all-cause mortality, and secondary outcomes were MV and vasopressors. Multivariable Cox regression models were performed to explore factors associated with the outcomes. Results: Overall, 80.1% had severe COVID-19, all-cause mortality was 8.9%, 12.8% required MV, and 11.2% received vasopressor support. Older patients with underlying comorbidities were more likely to have severe COVID-19. There was association between elevated aminotransferases and total bilirubin with more severe COVID-19. Hepatic decompensation was independently associated with all-cause mortality (HR 2.94; 95% CI 1.23-7.06). Alcohol-related liver disease (ALD, HR 2.79, 95% CI, 1.00-8.02) was independently associated with increased risk for MV, and independent factors related to vasopressor support were chronic pulmonary disease and underlying malignancy. Conclusions: COVID-19 infection in patients with CLD is associated with poor outcomes. SARS-CoV-2 infection in patients with hepatic decompensation was associated with an increased risk of in-hospital mortality hazard, and ALD among patients with COVID-19 was associated with an increased hazard for MV.

Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis C patients.

BACKGROUND: Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases. Fibrosis progression varies markedly in patients with hepatitis C virus (HCV). Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV. AIM: To investigate changes in liver stiffness measured by transient elastography (TE) in a large, racially diverse cohort of United States patients with chronic hepatitis C (CHC). METHODS: We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral (DAA) therapy and untreated patients. Patients had ≥ 2 TE measurements and no prior DAA exposure. We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment, controlling for age, sex, race, diabetes, smoking status, human immunodeficiency virus status, baseline alanine aminotransferase, and baseline liver stiffness. Separate regression models analyzed the change in liver stiffness as measured by kPa, stratified by cirrhosis status. RESULTS: Of 813 patients, 419 (52%) initiated DAA treatment. Baseline liver stiffness was 12 kPa in 127 (16%). Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients, respectively. There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment (0.016 kPa/month; CI: -0.051, 0.084) or in the untreated group (0.001 kPa/mo; CI: -0.090, 0.092), controlling for covariates. A higher baseline kPa score was independently associated with decreased liver stiffness. CONCLUSION: DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.

Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms.

BACKGROUND AND AIMS: Management of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH. METHODS: We studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI). RESULTS: The NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively). CONCLUSION: We validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.

Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients.

BACKGROUND: Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood. AIM: We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality. METHODS: This retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis. RESULTS: A total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilation. CONCLUSION: Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient's severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.

The Impact of Dietary Patterns and Nutrition in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver disease worldwide. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary patterns, and metabolic syndrome. Currently, in the absence of approved pharmacologic treatment, the keystone of treatment is lifestyle modification focused on achieving a weight loss of 7%-10%, cardiovascular exercise, and improving insulin sensitivity. The primary aim of this review is to outline the effect of different dietetic approaches against NAFLD and highlight the important micronutrient components in the management of NAFLD.

COVID-19: An overview and a clinical update.

The outbreak of coronavirus disease-2019 (COVID-19, previously known as 2019 nCoV) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan City, China, has spread rapidly around the world. Most patients from the first cluster had an epidemiological connection to the Wuhan's Huanan Seafood Wholesale Market. Available evidence has shown that SARS-CoV-2 can be easily transmitted from person to person through close contact and respiratory droplets, posing a substantial challenge to public health. At present, the research on SARS-CoV-2 is still in the primary stages. However, dexa-methasone and remdesivir are appeared to be promising medical therapies. Still, there is no definite specific treatment, and the mainstay of treatment is still focused on supportive therapies. Currently, over 150 vaccines are under investigation. It is necessary to understand the nature of the virus and its clinical characteristics in order to find effectively manage the disease. The knowledge about this virus is rapidly evolving, and clinicians must update themselves regularly. The present review comprehensively summarizes the epidemiology, pathogenesis, clinical characteristics, and management of COVID-19 based on the current evidence.

A Mimic of Hepatic Encephalopathy: Two Cases of Cryptococcal Meningitis in North America.

In the non-human immunodeficiency virus infected population, cryptococcosis occurs primarily in people who are functionally immunosuppressed, including patients who have undergone solid organ transplantation requiring immunosuppressive medications, are on corticosteroids, or have renal failure or cirrhosis. Cryptococcal meningitis poses a particular challenge in the setting of cirrhosis because its clinical presentation can mimic hepatic encephalopathy. Here, we describe two patients with decompensated cirrhosis, both with a known history of hepatic encephalopathy who had lumbar punctures and were found to have cryptococcal meningitis. The first patient had a subacute fluctuating change in mental status, while the second patient had progressive subacute headaches, gait disturbance, and hearing loss. Both patients were treated with amphotericin B and flucytosine induction, but only the second survived to maintenance therapy. These cases demonstrate the importance of having a high index of suspicion for cryptococcal meningitis in cirrhosis and having a low threshold for performing a lumbar puncture when altered mental status or other neurologic complaints are not fully explained by hepatic encephalopathy. We also provide a brief review of the pathobiology of cryptococcal infection in cirrhosis and highlight the challenges in therapy.

Pre- Versus Posttransplant Treatment of Hepatitis C Virus With Direct-Acting Antivirals in Liver Transplant Recipients: More Issues to be Solved.

OBJECTIVES: Our goal was to investigate wait times related to hepatitis C virus treatment with direct acting antivirals before versus after liver transplant at a single center as well as wait times for insurance approval for preemptive treatment with these agents after liver transplant. MATERIALS AND METHODS: We retrospectively evaluated hepatitis C virus infections in transplant recipients of deceased liver donations in 2014 and 2015. Demographics, hepatocellular carcinoma incidence, Model for End-Stage Liver Disease scores, and transplant wait times were compared between patients treated before or after liver transplant. Wait times to approval of direct-acting antiviral treatment were evaluated in those untreated before transplant. RESULTS: During our study period, of 67 deceased-donor liver transplants, 21 patients received hepatitis C virus treatment pretransplant (treated group) and 46 patients were not treated pretransplant (untreated group). Twenty-five patients in the untreated group received hepatitis C virus-positive donations, with all in this group treated with direct-acting antivirals. We found no statistically significant differences regarding age, sex, race, donation after cardiac death, or incidence of hepatocellular carcinoma between groups. The treated group had a longer median wait time (287 vs 172 days; P = .02). Twelve of the 46 untreated patients (26.1%) developed biopsy-proven hepatitis C virus-related relapse (median 87 days; range, 55-383 days). Preemptive direct-acting antiviral therapy was initiated at a median of 81 days in the untreated group. CONCLUSIONS: Although treatment of hepatitis C virus before liver transplant is an attractive option to eliminate the risk of complications, it can limit the donor pool for recipients to uninfected donors, significantly increasing wait times in regions with large hepatitis C virus-positive donor pools. Allocation of Model for End-Stage Liver Disease score was not different between the treated and untreated groups. Insurance companies should revise their policies for rapid approval of preemptive direct-acting antiviral treatment after liver transplant.

Effect of prior hepatitis B virus exposure on long-term risk of liver-related events after liver transplantation.

OBJECTIVE: To characterize the risk of liver-related events and death in hepatitis B virus (HBV)-exposed liver transplantation (LT) recipients. METHODS: Retrospective review was performed in all adults who underwent LT between January 1995 through December 2010 at the Johns Hopkins Hospital. Recipients with graft failure or death within 14 d of LT or missing HBV status were excluded, leaving 575 individuals for analysis. Patients were classified according to HBV exposure status: Unexposed, Resolved HBV, Chronic HBV, or hepatitis B core antibody (anti-HBc) seropositive liver donor. RESULTS: Compared with HBV-unexposed patients, the relative hazard of combined liver-related events (rejection, cirrhosis, re-transplantation) and death after LT was not increased in patients with a baseline history of resolved HBV infection or chronic hepatitis B. Using anti-HBc seropositive donors also did not increase the risk of liver-related events, death, or composite events (all p ≥ 0.05). However, hepatitis C was associated with liver-related events [adjusted hazard ratio (aHR), 1.59; 95% confidence interval (CI), 1.00-2.52], and blacks had a higher risk of death (aHR, 1.50; 95% CI, 1.01-2.22). CONCLUSION: LT of patients with prior HBV exposure or use of anti-HBc seropositive donors is not associated with increased risk of liver-related events or death.

Evaluation of abnormal liver tests.

The routine use of serum biochemical tests allows for the detection of acute and chronic liver injury before the onset of symptoms. These tests consist of markers of hepatocellular injury (aminotransferases and APs); tests of liver metabolism (total bilirubin); and tests of liver synthetic function (serum albumin and PT). Noninvasive tests for assessment of liver fibrosis are promising tools for diagnosis and prognosis of patients with chronic liver disease. A comprehensive history, physical examination, and assessment of pattern of liver injury with additional laboratory and imaging testing establish the cause of hepatobiliary disease in most cases.

Incidence and risk factors for steatosis progression in adults coinfected with HIV and hepatitis C virus.

BACKGROUND & AIMS: Hepatic steatosis is a common histologic finding in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients coinfected with HIV and HCV who attended an urban HIV clinic. METHODS: The study cohort consisted of 222 coinfected patients (87% black, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsy specimens were scored by a single pathologist; samples were classified as having trivial (<5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression. RESULTS: Initial biopsy specimens from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for progression of steatosis were alcohol abuse and overweight/obesity; cumulative exposure to antiretroviral therapy between biopsies and high counts of CD4(+) T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy specimen had significant fat levels, most (75%) regressed. CONCLUSIONS: Antiretroviral therapy and high counts of CD4(+) T cells are associated with reduced progression of steatosis in patients coinfected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with a high body mass index and excessive alcohol intake.