The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients.

Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.

Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States.

Background :   Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI). Methods: Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves. Results: MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011). Conclusion: In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

Facing the Unknown: Idiopathic Giant Cell Hepatitis.

Giant cell hepatitis is a rare infiltrative disease associated with several viruses, drugs, malignancies, and autoimmune conditions. To date, treatment aims at controlling the underlying etiology, and there are limited data on the clinical course and treatment of idiopathic cases. We present a case of idiopathic giant cell hepatitis in an otherwise healthy adult man and review the literature regarding treatment and outcomes in this population.

Granulocyte colony-stimulating factor does not improve mortality in severe alcoholic hepatitis: a single-center experience from the United States.

Aim: To assess the role of granulocyte colony-stimulating factor (GCSF) in the patients with severe alcoholic hepatitis (SAH) using real world experience in the United States. Background: There are few effective treatments for severe alcoholic hepatitis, which has a significant fatality rate. GCSF has been associated with improved survival in a small number of Indian studies, while there is a dearth of information from other parts of the globe. Methods: We performed a single-center retrospective study of consecutive patients admitted to a tertiary care, liver transplant center with severe alcoholic hepatitis from May 2015 to February 2019. The patients receiving GCSF (5µg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to the patients receiving standard of care (n=42). Results: Thirty-day, 90-day and 1-year mortality rates was similar among groups (25% vs. 17%, P=0.58; 41% vs 29%, P=0.30; 41% vs 47%, P=0.44, respectively). There was no difference in liver transplant listing and orthotopic transplantation among groups. Conclusion: In this real-world, United States-based study, GCSF does not improved survival in the patient with several alcoholic hepatitis compared to standard of care.

Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury.

The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.

A Diagnostic Paracentesis Leading to Intra-abdominal Hematoma and Small Bowel Obstruction.

It is rare for patients to have hemorrhagic complications after abdominal paracentesis. Abdominal wall hematomas and hemoperitoneum are the most common hemorrhagic complications of paracentesis. The incidence rate of hemorrhage-related complications is unknown. The risk of hemorrhage-related complications can be elevated in patients with underlying kidney disease and those who are thrombocytopenic or coagulopathic. However, there is no correlation between the degree of thrombocytopenia or coagulopathy and the risk of bleeding. It is important to identify the high-risk patients to prevent these hemorrhage-related complications. In rare instances, secondary complications can develop from hemoperitoneum. We present a case of a cirrhotic patient who underwent a diagnostic paracentesis leading to subsequent intra-abdominal hematoma followed by small bowel obstruction (SBO) due to large abdominal hematoma compressing small bowel loops.

A Peculiar Peritoneum: A Case of Tuberculosis in a Male Without Known Risk Factors.

Peritoneal tuberculosis is an uncommon diagnosis in developed countries and most commonly presents in patients with known risk factors for tuberculosis. We report a case of a patient without tuberculosis risk factors who presented with 4 years of intermittent fevers, several weeks of increasing abdominal distention, and newly discovered elevated liver tests. The diagnosis of peritoneal tuberculosis was confirmed following an extensive workup with a positive ascitic fluid culture for Mycobacterium tuberculosis. The patient's fevers resolved with antibiotic therapy, and antibiotic therapy was subsequently de-escalated based on the susceptibility profile.

Comparison of 1-Year Morbidity Following Liver Transplant for Acute Alcoholic Hepatitis Versus Alcoholic Cirrhosis.

OBJECTIVES: With limited data on the morbidity profile of liver transplant as therapy for alcoholic hepatitis, we compared 30-day and 1-year morbidity in liver transplant recipients with alcoholic hepatitis versus alcoholic cirrhosis. MATERIALS AND METHODS: We retrospectively reviewed 38 perioperative variables in patients with alcoholic hepatitis (n = 15) and with alcoholic cirrhosis (n = 46). Multivariable analysis was performed to identify factors independently associated with outcomes. RESULTS: Patients with alcoholic hepatitis were younger (43 vs 58 years; P = .001), with higher pretransplant Model for End-Stage Liver Disease scores (36 vs 29; P = .009) and worse Karnofsky scores (20 vs 50; P < .001). All patients with alcoholic hepatitis received standard criteria deceased donor grafts; however, in the alcoholic cirrhosis group, 64% received standard criteria deceased, 11% living, 11% after cardiac death, 9% extended criteria, and 2% split graft donor organ donations (P > .05). The alcoholic hepatitis group had higher degree of steatosis on explant (P < .005), and the alcoholic cirrhosis group had higher 30-day reoperation rate (P = .001); however, 1-year interventions, vascular and biliary complications, graft and patient survival, and all other variables were similar (P > .05). Rates of alcohol relapse, 1-year infection, and 1-year rejection were higher but not significant (P > .05) in the alcoholic hepatitis group. Thirty-day reoperation (odds ratio of 82.63; 95% CI, 8.02-3338.96; P = .002) and Karnofsky scores (odds ratio of 1.18; 95% CI, 1.08-1.36; P = .006) remained significant on multivariate analysis. CONCLUSIONS: Our results showed significant differences between our patient groups, including worse functional status in the alcoholic hepatitis group but significantly higher 30-day reoperation rates and more variable grafts in the alcoholic cirrhosis group, although both groups had similar overall 1-year complication and survival rates. Although not significant, patients with alcoholic hepatitis had higher alcohol relapse and 1-year infection and rejection rates. A larger cohort is necessary to confirm the strength of these findings.

Ineffective Absorption? Failure of Direct-Acting Therapy for Chronic Hepatitis C in Cirrhotic Patients With Roux-en-Y Gastric Bypass.

In this era of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection, treated patients have extremely high rates of sustained virologic response to short courses of therapy regardless of stage of fibrosis. Treatment failure is uncommon and often attributed to medication noncompliance or viral resistance to drug. This report describes 2 Child-Pugh-A cirrhotic patients who failed to clear HCV in response to therapy with DAAs. Each patient had Roux-en-Y gastric bypass (RYGB) surgery preceding DAA therapy. RYGB may create multiple barriers to adequate DAA absorption as a result of changes in gastrointestinal physiology. Treatment monitoring and duration should be carefully considered in this unique patient population.