Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC. METHODS: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts. RESULTS: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy. CONCLUSIONS: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

Postprandial Plasma Lipidomics Reveal Specific Alteration of Hepatic-derived Diacylglycerols in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.

Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity.

Inborn errors of immunity (IEIs) consist of numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States. As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges. A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity. A generalized approach to diagnosis and management of hepatic complications is provided, and collaboration with hepatologists, immunologists, and pathologists is emphasized as a requirement for optimizing management and outcomes.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients.

BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

Immunogenicity and Adverse Effects of the 2-Dose BNT162b2 Messenger RNA Vaccine Among Liver Transplantation Recipients.

The BNT162b2 messenger RNA (mRNA) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be safe and effective in immunocompetent patients. The safety and efficacy of this vaccine in liver transplantation (LT) recipients is still under evaluation. The objective of this study was to assess the safety and efficacy of the BNT162b2 vaccine among transplant recipients. The immune responses of 76 LT recipients receiving 2 doses of the vaccine were compared with those of 174 age-matched immunocompetent controls. Postvaccination immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 and neutralizing antibodies (NA) to the BNT162b2 mRNA vaccine were determined at least 14 days after the second dose of the vaccine. IgG antibody titers ≥1.1 were defined as positive antibodies. Adverse effects were monitored during the study period. Following administration of the second dose, transplant recipients showed reduced immune responses compared with controls (72% versus 94.2%; P < 0.001). At a median time of 38 days after the second vaccination, the geometric mean of RBD IgG and NA titers were 2.1 (95% confidence interval [CI], 1.6-2.6) and 150 (95% CI, 96-234) among transplant recipients and 4.6 (95% CI, 4.1-5.1) and 429 (95% CI, 350-528) in the control group, respectively (P < 0.001). Antibody responses were lower in transplant recipients who were receiving combined immunosuppression therapy and in those with impaired renal function. Among the LT recipients with negative antibody responses, 1 became infected with SARS-CoV-2, but no recipients with positive antibody responses became infected. Overall, most (n = 39 [51%]) adverse effects self-reported by transplant recipients were mild and occurred more often in women than in men. Compared with patients who were immunocompetent, LT recipients had lower immune responses. The durability of immune responses to the BNT162b2 vaccine among LT recipients requires further investigation.

Roadmap to resuming care for liver diseases after coronavirus disease-2019.

The global pandemic of coronavirus disease-2019 (COVID-19) has led to significant disruptions in healthcare delivery. Patients with chronic liver diseases require a high level of care and are therefore particularly vulnerable to disruptions in medical services during COVID-19. Recent data have also identified chronic liver disease as an independent risk factor for COVID-19 related hospital mortality. In response to the pandemic, national and international societies have recommended interim changes to the management of patients with liver diseases. These modifications included the implementation of telehealth, postponement or cancelation of elective procedures, and other non-urgent patient care-related activities. There is concern that reduced access to diagnosis and treatment can also lead to increased morbidity in patients with liver diseases and we may witness a delayed surge of hospitalizations related to decompensated liver disease after the COVID-19 pandemic has receded. Therefore, it is paramount that liver practices craft a comprehensive plan for safe resumption of clinical operations while minimizing the risk of exposure to patients and health-care professionals. Here, we provide a broad roadmap for how to safely resume care for patients with chronic liver disease according to various phases of the pandemic with particular emphasis on outpatient care, liver transplantation, liver cancer care, and endoscopy.

The Spectrum of Hepatic Involvement in Patients With Telomere Disease.

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.

Vibration Controlled Transient Elastography (Fibroscan®) in sickle cell liver disease - could we strike while the liver is hard?

Vibration controlled transient elastography (VCTE) is validated for the evaluation of hepatic fibrosis in different liver diseases. Sickle cell liver disease (SCLD) results from a cumulative hepatic injury and its lifelong and progressive nature raises the need for a non-invasive tool for fibrosis evaluation. Fifty patients, aged between 23 and 59 years with sickle cell disease and suspected SCLD underwent a VCTE followed by a liver biopsy. Biopsies were evaluated for various scores of liver disease that were then correlated to VCTE score. 90% of our patients had an Ishak Fibrosis (IF) score between 0-2 (Group A-minimal to no fibrosis) and 10% of the patients had IF score between 3-6 (Group B-advanced fibrosis). The median Transient Elastography (TE) for patients in Groups A and B was 4·8 kilopascals (kPa) and 17·6 kPa, respectively. A positive correlation was shown between TE and IF score, R = 0·0·68 (P = <0·0001); a positive correlation was also shown with Histology Activity Index fibrosis score, R = 0·64 (P = <0·0001). This study emphasises the need for further studies of non-invasive tools and their utility in liver fibrosis evaluation of patients with SCLD.

[FIRST GENERATION PROTEASE INHIBITOR BASED TRIPLE THERAPY FOR HCV GENOTYPE 1--LOOKING BACK WHILE PROCEEDING TO A PROMISING ERA].

BACKGROUND: For the last decade the backbone of hepatitis C (HCV) treatment was the pan-genotyping dual therapy with pegylated interferon alfa in combination with Ribavirin. This regimen was limited in achieving sustained virological response (SVR) and accompanied by serious adverse events. In 2010 there was overwhelming progress in the treatment options for HCV. This change began with the introduction of the first generation specific Direct Antiviral Agents (DAA's) that inhibit the viral protease, agents used in combination with the dual protocol for genotype 1 (triple therapy). In 2014 this revolution continued with the introduction of advanced DAA's targeting different non-structural viral proteins. These DAA's achieve an all oral regimen shorter in duration with outstanding SVR rates and mild side effects. Our liver clinic manages the treatment and follow-up of the vast majority of patients with HCV in southern Israel. As part of the unprecedented advance in the treatment regimen for HCV with the introduction of the first generation DAA's and especially after they were included by the national health care as an option for treatment, we started to treat HCV genotype 1 patients with the triple regimen. Now, in the era of advanced DAA's regimens, we look back, retrospectively, analyze and conclude our experience with a regimen that changed the conception of eradication for HCV by combining immune activation and specific inhibition of functional viral proteins. This was conducted in the hope that it will inspire the development of revolutionary regimens for eradication in other viral diseases. METHODS: During the period between September 2011 to November 2013, 55 patients infected with HCV genotype 1 were treated in our outpatient liver clinic with the triple regimen. These patients finished a 6 month period of post-treatment follow-up allowing the evaluation of their viral PCR status at the latest in May 2014. The data were collected from the patient's computerized file and were statistically analyzed by the SMC clinical research center. RESULTS: Out of the 55 patients, 39 received Telaprevir as the protease inhibitor and 16 were treated with Boceprevir. Of all the treated patients 34 achieved SVR; 47% of patients with genotype 1A reached SVR, whereas 71% of those with genotype 1B reached that endpoint. A total of 63.6% of patients with mild or no fibrosis (F 0-2) achieved SVR compared to 63% in patients with advanced fibrosis (F 3-4]. There were 6 patients with no METAVIR evaluation. A total of 57% of naïve patients, 83.3% of prior relapsers and 57.1% of previous non-responders reached SVR at 6 months in current triple therapy. There was no significant response difference in any sub-group when the two first generation PI's were compared. CONCLUSIONS: In our experience with first generation PI based triple regiment for HCV genotype 1, though more effective than previous dual treatment, it was still limited in its effectiveness, while creating some major safety issues. In light of this new era where much more effective and safe DAA's emerged and are now in routine use, the triple therapy in our view should be reviewed as a transitional phase that changed forever the concept of eradicating HCV and aimed at specific viral sites. This regimen paved the way for advanced DAA protocols achieving cures in overwhelming unprecedented rates.

Efficacy and long-term durability of intradermal recombinant hepatitis B virus vaccine among intramuscular vaccine nonresponders: A prospective study in healthcare personnel.

BACKGROUND: Data on efficacy, safety, and durability of intradermal vaccine administration in persons who have not responded appropriately to intramuscular administration of hepatitis B virus (HBV) vaccine are relatively scarce. METHODS: We designed a prospective case series in an urban tertiary care hospital in Israel. The medical records of 4007 healthcare personnel who had worked in the hospital between 1996 and 2006 were examined and those with an unsatisfactory level (<10 mIU/ml) of hepatitis B surface antibody (HBsAb) following two courses of a three-dose intramuscular HBV vaccine ("nonresponders") were identified. Nonresponders were vaccinated with three doses of 5 µg of intradermal recombinant hepatitis B surface antigen-based vaccine at weeks 0, 2, and 4. Level of HBsAb was determined 4 weeks after the last dose, and an additional dose was administered as needed. HBsAb level was again determined 24 weeks after the final vaccine dose to assess late immune reactivity and long-term durability of the vaccine. Vaccine safety was assessed at each vaccination and testing session. RESULTS: Twenty-seven subjects were included in the study, and 21 completed the study. The proportion of subjects with satisfactory HBsAb level at 4 weeks after the last administered dose was 70.3% (19/27). The proportion of subjects with sustained immune response at 24 weeks was 62.9% (17/27) according to intention-to-treat analysis and 80.9% (17/21) according to per protocol analysis. There were no reports of adverse events in response to the administration of the vaccine. CONCLUSIONS: Intradermal administration of HBV vaccine offers an efficient, safe, and durable option for intramuscular vaccine nonresponders and represents a means to optimize utilization of the widespread HBs antigen-based vaccine formulation.

Time to Publication for Randomized Clinical Trials Presented as Abstracts at Three Gastroenterology and Hepatology Conferences in 2017.

Background & Aims: Results of randomized clinical trials are often first presented as conference abstracts, but these abstracts may be difficult to find, and trial results included in the abstract may not be followed by subsequent journal publications. In a review of abstracts submitted to eight major medical and surgical conferences in 2017, we identified 237 abstracts reporting primary results of randomized clinical trials accepted for presentation at three major gastroenterology and hepatology conferences. The aims of this new analysis were to determine the publication rate for these abstracts and the proportion of publications that included trial registration numbers in the publication abstract. Methods: Clinical trial registries, PubMed, Europe PMC, and Google Scholar were searched through November 1, 2021, for publications reporting trial results for the selected abstracts. Publications were reviewed to determine if they included a trial registration number and if the registration number was in the abstract. Results: Publications were found for 157 abstracts (66%) within four years of the conference. Publications were found more frequently for the 194 abstracts reporting results of registered trials (144, 74%) than for the 43 abstracts reporting unregistered trials (13, 30%), but only 67% of these 144 publications included the registration number in the publication abstract. Ten unpublished trials had summary results posted on ClinicalTrials.gov. Conclusions: Clinical trial results could be more accessible if all trials were registered, authors included registration numbers in both conference and journal abstracts, and journal editors required the inclusion of registration numbers in publication abstracts for registered clinical trials.

Predictors of advanced liver fibrosis and the performance of fibrosis scores: lean compared to non-lean metabolic dysfunction-associated steatotic liver disease (MASLD) patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) in lean patients differs from that of NAFLD in non-lean patients. However, current data regarding predictors of advanced fibrosis and the performance of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) in lean compared to non-lean metabolic dysfunction-associated steatotic liver disease (MASLD) patients is insufficient. METHODS: This was a cross-sectional study. Lean was defined as Body Mass Index <25 kg/m2. Advanced fibrosis (F3-F4) was detected by liver biopsy or two-dimension shear wave elastography (2D-SWE). Predictors of advanced fibrosis were identified using logistic regression and area under ROC curves (AUROC) were derived for FIB-4 and NFS. RESULTS: Lean patients (N.=153) comprised 19.2% of the MASLD cohort. Advanced fibrosis was associated with the number of cardiometabolic risk factors (CMRF) in lean (OR=2.06, P=0.011) and non-lean (OR=1.58, P<0.001) patients, however, hypertension and diabetes or impaired fasting glucose were significant only among non-lean. Age was associated with advanced fibrosis in both subgroups with age ≥65 showing higher odds in lean compared to non-lean patients (P=0.016). Non-lean patients had higher odds for advanced fibrosis relative to lean patients (OR=4.8, P=0.048). FIB-4 and NFS predicted advanced fibrosis among lean (AUROC=0.79 and AUROC=0.85, respectively) and non-lean (AUROC=0.79 and AUROC=0.76, respectively) patients. NFS ≥-1.445 showed higher specificity among lean compared to non-lean (P<0.001) and compared to that of FIB-4 ≥1.3 in lean patients (P<0.001). CONCLUSIONS: The number of CMRF was predictive of advanced fibrosis in both subgroups while age ≥65 showed higher odds among lean patients. NFS ≥-1.445 is more specific than FIB-4 ≥1.3 for advanced fibrosis prediction in lean patients. These findings may help identify high-risk lean MASLD patients for further liver fibrosis stage assessment.

Research trends analysis of chronic hepatitis C versus nonalcoholic fatty liver disease: A literature review text-mining analysis of publications.

Background: Hepatits C virus (HCV) rates have lowered due to direct-acting antiviral treatment. Nonalcoholic steatohepatitis (NASH)/nonalcoholic fatty liver disease (NAFLD) is rising with no available therapy. We employed text-mining to analyze trends in HCV and NAFLD research from the past two decades. Materials and Methods: We queried PubMed for all HCV and NASH/NAFLD entries published between 2000 and 2020. We compared the total number of publications on both etiologies. We performed subanalyses for different terms of interest and for geographic origin. Results: Overall, 75,934 HCV-related entries and 24,987 NASH/NAFLD-related entries were published during the study period. Up to 2015, there was a linear upward slope in the number of annual HCV publications (154.9 publications/year, p < 0.001). In 2015, the yearly number of HCV publications started showing a downward slope (-242.2 publications/year, p < 0.001). The number of NASH/NAFLD publications showed a continuous upward slope during the study period. The NASH/NAFLD field lacks publications on screening and treatment methods. Conclusion: Trends in publications varied between both etiologies. They reflect the success of antiviral treatment for HCV. The growing rates of NAFLD/NASH and the lack of a targeted cure explain the rise in related publications.

HBV-RNA, Quantitative HBsAg, Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B.

A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load >1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n = 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p < 0.05). HBV genotype D prevailed (61/68), and >95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.

Lipoprotein Insulin Resistance Index Reflects Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease.

The recently developed lipoprotein insulin resistance index (LP-IR) incorporates lipoprotein particle numbers and sizes and is considered to reflect both hepatic and peripheral IR. As tissue IR is a strong component of nonalcoholic fatty liver disease (NAFLD) pathogenesis, we aimed to assess the degree by which LP-IR associates with hepatic fat content. This was a single-center retrospective analysis of patients with NAFLD. LP-IR, the homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue IR (Adipo-IR) were measured simultaneously. Liver fat content was estimated by FibroScan controlled attenuated parameter. Associations were assessed using Spearman's correlation and multivariate linear regression. The study included 61 patients. LP-IR was correlated with HOMA-IR (ρ = 0.30; P = 0.02), typically thought to reflect hepatic IR, but not with Adipo-IR (ρ = 0.15; P = 0.25). Liver fat content was significantly associated with Adipo-IR (ρ = 0.48; P < 0.001), LP-IR (ρ = 0.35; P = 0.005), and to a lesser degree with HOMA-IR (ρ = 0.25; P = 0.051). The association of liver fat with LP-IR was limited to patients without diabetes (ρ = 0.60; P < 0.0001), whereas no association was seen in those with diabetes. In a multivariate model, Adipo-IR, LP-IR, and diabetes were independently associated with liver fat and together explained 35% of the variability in liver fat. Conclusion: LP-IR is a reasonable measure of IR in non-diabetic patients with NAFLD and is associated with hepatic fat content. Although adipose tissue is the major contributor to liver fat, the additional contribution of nonadipose tissues can be easily estimated using LP-IR.

The liver in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

BACKGROUND: The ongoing outbreak of COVID-19 is associated with higher levels of morbidity and mortality among patients with comorbidities, including the metabolic syndrome. Liver impairment has been reported in up to 54% of hospitalized patients with COVID-19. The impact of COVID-19 on a preexisting chronic liver disease is an actively studied area of research. The contribution of our study is towards determining the predictors of severity and the outcome of liver injury among hospitalized patients with COVID-19 infection, including patients with a preexisting liver disease and COVID-19. METHODS: This single center retrospective cohort study included all patients ≥18 years, admitted in Sheba Medical Center with confirmed COVID-19 infection. Demographic, clinical and laboratory data were obtained using the MDClone platform and rechecked after data decryption using electronic health records. RESULTS: Of 382 patients with COVID-19, 66.4% had increased liver biochemistry. Mild increase was observed in 76.7%. The higher level of fibrosis-4 (FIB-4) at admission was independently associated with higher mortality rate. Preexisting liver disease was detected in 15.4% patients. Most common etiology was nonalcoholic fatty liver disease (78.7%). The mortality of hospitalized patients with preexisting liver disease was 16.7% compared to 6.8% in patients without preexisting liver disease (RR = 2.792, P = 0.01). In multivariate analysis, liver disease adjusted to age and BMI was associated with mortality with high statistical significance. CONCLUSIONS: Patients with preexisting chronic liver disease were at a higher risk of mortality. The FIB-4 level at admission was associated with worse prognosis. These findings should be reevaluated in a larger cohort of patients.