A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction.

Addressing drug-induced liver injury is crucial in drug development, often causing Phase III trial failures and market withdrawals. Traditional animal models fail to predict human liver toxicity accurately. Virtual twins of human organs present a promising solution.

External Validation of Four Point-of-Care Noninvasive Scores for Predicting Advanced Hepatic Fibrosis in a Predominantly Hispanic NAFLD Population.

Background: The development of point-of-care biomarkers of disease has become a major focus of interest in nonalcoholic fatty liver disease (NAFLD). The NAFLD fibrosis score (NFS), BARD, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) are commonly used for advanced NAFLD fibrosis prediction. However, the performance of these scores among in a predominantly Hispanic patient population, a population with the highest prevalence of NAFLD, has not been examined.

Stauffer Syndrome: A Comprehensive Review of the Icteric Variant of the Syndrome.

Stauffer syndrome is a rare paraneoplastic syndrome classically associated with renal cell carcinoma (RCC). This association gave it the historical name of nonmetastatic nephrogenic hepatic dysfunction syndrome without jaundice. It is a syndrome of unclear pathophysiology characterized by a reversible anicteric elevation of liver enzymes, alkaline phosphatase, erythrocyte sedimentation rate (ESR), thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly in the absence of direct hepatobiliary obstruction or jaundice.

Macro-aspartate Aminotransferase: Misleading Finding in a Patient with Non-alcoholic Fatty Liver Disease.

Persistent elevation of aspartate aminotransferase (AST) activity in serum due to the presence of a macro-enzyme form of AST (macro-AST) may lead to diagnostic confusion in many clinical conditions, particularly in those associated with chronic liver disease. We present a case of macro-AST in a patient with non-alcoholic fatty liver disease in which polyethylene glycol precipitation confirmed the cause of disproportionately elevated AST as macro-AST.

Autoimmune Hepatitis Refractory to Treatment Due to Underlying Grave's Disease.

A 24-year-old Hispanic woman presented to our facility with a two-week history of abdominal pain, nausea, vomiting, diarrhea, jaundice, and scleral icterus. Initial laboratory workup revealed elevated transaminases, direct hyperbilirubinemia, and positive anti-smooth muscle antibody. Liver biopsy confirmed the diagnosis of autoimmune hepatitis and our patient was started on oral prednisone therapy.

Pathogenesis of Alcoholic Liver Disease: An Update.

Apart from the classic knowledge that ethanol mediates its hepatotoxicity through its metabolism to acetaldehyde, a well-known hepatotoxic molecule, recent research has elucidated several key mechanisms that potentiate ethanol's damage to the liver parenchyma, such as generation of free radicals, activation of Kupffer cells, and alterations to the human bacterial and fungal microbiome. Genetic studies have suggested the role of PNPLA3 and TM6SF2 gene mutations in the progression of alcoholic liver disease.

Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease.

Obesity now affects millions of people and places them at risk of developing metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models, time-restricted feeding resets the hepatic circadian clock and enhances transcription of key metabolic regulators of glucose and lipid homeostasis.

Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis.

The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter.

Liver transplant length of stay (LOS) index: A novel predictive score for hospital length of stay following liver transplantation.

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation.

Non-alcoholic fatty liver disease and cardiovascular risk.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with insulin resistance and metabolic syndrome. The spectrum of disease ranges from simple steatosis to steatohepatitis and progression to cirrhosis. Compelling evidence over the past several years has substantiated a significant link between NAFLD and cardiovascular disease ranging from coronary artery disease to subclinical carotid atherosclerosis.

Plasmapheresis for Refractory Pruritus due to Drug-Induced Cholestasis.

Pruritus can be a distressing symptom seen in various cholestatic disorders. It is treated with medications like bile acid sequestrants. Drug-induced cholestasis usually resolves with withdrawal of the causative medication.

Everolimus with early withdrawal or reduced-dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta-analysis.

Calcineurin inhibitors (CNI) are the mainstay of immunosuppression after liver transplantation (LT), but CNIs are associated with significant nephrotoxicity. Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) that examined the effect of EVR with CNI minimization or withdrawal on renal function in LT recipients.

Hepatitis C Associated B-cell Non-Hodgkin Lymphoma: Clinical Features and the Role of Antiviral Therapy.

The link between chronic hepatitis C virus (HCV) infection and a subset of B-cell non-Hodgkin lymphomas (B-NHL) is strongly supported by epidemiological studies. Evidence demonstrating complete regression of lymphoma after antiviral treatments suggests possible chronic antigenic stimulation for the origin of B-NHL and provides evidence for a virus-mediated lymphomagenesis. B-NHL is a heterogeneous group of lymphomas with varied clinical presentation and may be indolent or aggressive.

Hepatocellular carcinoma review: current treatment, and evidence-based medicine.

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC including curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach.

Time course of collagen peak in bile duct-ligated rats.

Background: One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials.

CYP1A2*1F and GSTM1 alleles are associated with susceptibility to porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1.

Hepatotoxicity fears contribute to underutilization of statin medications by primary care physicians.

Introduction: The safety and efficacy of hydroxymethylglutaryl CoA reductase inhibitors (statins) have been extensively demonstrated, but in clinical practice, there remains significant underutilization of these medications. The authors hypothesized that this underutilization could stem in part from fear of liver damage caused by statins. The purpose was to determine whether concern about hepatotoxicity acts as a barrier among primary care physicians to prescribing statins for patients with elevated liver transaminase values and/or underlying liver disease.

Terlipressin therapy for reversal of type 1 hepatorenal syndrome: a meta-analysis of randomized controlled trials.

Background And Aim: Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease and carries a poor prognosis. Recent trials have indicated that terlipressin may be effective in reversing HRS. Our aim was to evaluate the efficacy of terlipressin therapy in reversing type 1 HRS defined as a serum creatinine <1.

Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

Background & Aims: The effects of antiviral therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis are unclear. We performed a systematic review and meta-analysis to assess HCC risk reduction in patients with HCV-related cirrhosis who have received antiviral therapy.

Methods: Twenty studies (4700 patients) were analyzed that compared untreated patients with those given interferon (IFN) alone or ribavirin.

Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: a literature review.

Background: Some porphyrias are associated with cutaneous phototoxicity due to photoactivation of porphyrins, but whether ionizing radiation can have an additive effect is not clear. We report a case of severe radiation therapy-related toxicity in a patient with porphyria cutanea tarda and review the literature.

Methods: A 50-year-old man with porphyria cutanea was treated for lower lip squamous cell carcinoma with definitive radiation therapy.

Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis.

Background & Aims: Weight loss in overweight or obese individuals results in marked improvement or resolution of hypertension, diabetes mellitus, and hyperlipidemia. However, the overall effect of weight loss on nonalcoholic fatty liver disease (NAFLD) remains unclear. This systematic review and meta-analysis is an effort to explore the effect of weight loss after bariatric surgical procedures on NAFLD.

Neutropenic enterocolitis: An unusual complication of HCV combination therapy with PEG-IFN and ribavirin.

Drug induced neutropenia as a consequence of intensive chemotherapy for hematological malignancies and solid tumors is known to be associated with severe, life-threatening infections such as neutropenic enterocolitis. However, the neutropenia associated with HCV combination therapy with Pegylated Interferon [PEG-IFN] and ribavirin is considered to be well tolerated in patients without other co-morbidities. We present a case of a severe gastrointestinal complication in a patient receiving HCV combination therapy and advocate caution in continuing therapy in patients with neutropenia, especially in the presence of underlying co-morbidities such as cirrhosis.

Serum prolidase and IGF-1 as non-invasive markers of hepatic fibrosis during four different periods after bile-duct ligation in rats.

Aim: Our aim was to study the correlation of serum prolidase and insulin like growth factor-1 to liver collagen and assess their utility as markers of fibrosis during four different periods of hepatic injury and fibrosis after bile-duct ligation in rats.

Methods: Forty-eight Wistar albino rats were included in the study and divided into six groups. Seven rats served as the control group (Control), while seven rats had a sham operation (Sham group).