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Purpose: Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time‐series (ITS) analyses, between 2014 and 2019. Method: Two quasi‐experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records. Results: Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period. Conclusion: Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long‐term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data. [ABSTRACT FROM AUTHOR]

Background: Savolitinib, a small molecule inhibitor, has gained approval as the inaugural medication in China that specifically targets MET kinase. Patients with advanced non-small cell lung cancer (NSCLC) who show MET exon 14 skipping now have a new and innovative treatment option available. Case report: In this case report, we describe a patient who experienced drug-induced liver injury (DILI) due to the administration of savolitinib. After being prescribed with savolitinib (400 mg per day, oral), a 73-year-old male diagnosed with stage IV NSCLC with MET exon 14 skipping mutation experienced an increase in liver enzymes and bilirubin levels according to his laboratory tests conducted one month later. Following a 14-day course of hepatoprotective medication, the liver function reverted back to its normal state. After receiving savolitinib (200 mg per day, oral) for one week, the patient was once again diagnosed with severe liver impairment. Then savolitinib was discontinued and received treatment with hepatoprotective drugs for one week. Following the restoration of normal liver function, another attempt was made to administer a small amount of savolitinib (100 mg per day, oral). Thus far, the patient has been followed up and there has been no recurrence of liver damage. Additionally, the lung CT scan revealed ongoing tumor shrinkage with no apparent indications of spreading or metastasis. The Roussel Uclaf Causality Assessment Method (RUCAM) determined that savolitinib was "highly probable" cause of DILI. Moderate-severe was determined to be the extent of DILI severity. Conclusion: To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual. [ABSTRACT FROM AUTHOR]

Abstract Background Savolitinib, a small molecule inhibitor, has gained approval as the inaugural medication in China that specifically targets MET kinase. Patients with advanced non-small cell lung cancer (NSCLC) who show MET exon 14 skipping now have a new and innovative treatment option available. Case report In this case report, we describe a patient who experienced drug-induced liver injury (DILI) due to the administration of savolitinib. After being prescribed with savolitinib (400 mg per day, oral), a 73-year-old male diagnosed with stage IV NSCLC with MET exon 14 skipping mutation experienced an increase in liver enzymes and bilirubin levels according to his laboratory tests conducted one month later. Following a 14-day course of hepatoprotective medication, the liver function reverted back to its normal state. After receiving savolitinib (200 mg per day, oral) for one week, the patient was once again diagnosed with severe liver impairment. Then savolitinib was discontinued and received treatment with hepatoprotective drugs for one week. Following the restoration of normal liver function, another attempt was made to administer a small amount of savolitinib (100 mg per day, oral). Thus far, the patient has been followed up and there has been no recurrence of liver damage. Additionally, the lung CT scan revealed ongoing tumor shrinkage with no apparent indications of spreading or metastasis. The Roussel Uclaf Causality Assessment Method (RUCAM) determined that savolitinib was “highly probable” cause of DILI. Moderate-severe was determined to be the extent of DILI severity. Conclusion To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual.

Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24–72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [18F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [18F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUVav) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [18F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUVav compared to controls (p = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [18F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF. [ABSTRACT FROM AUTHOR]

Introduction: Primary sclerosing cholangitis (PSC) is a complex liver disorder marked by multifocal bile duct strictures and dilatations, leading to cholestasis and liver fibrosis. Although the exact cause is unknown, autoimmune mechanisms are strongly suspected. Aim of the Study: This paper reviews current knowledge on PSC, covering its etiology, prevalence, treatment options, and practical management strategies. Current State of Knowledge: PSC management focuses on symptom relief and liver transplantation, with limited success in pharmacological treatments. New therapies, including immune modulators and anti-fibrotic agents, show promise but require further research. Liver transplantation remains the most effective treatment, though recurrence risks necessitate ongoing monitoring. Materials and Methods: This article reviews the current understanding of PSC, including its pathophysiology, diagnostic approaches, clinical features, and management strategies. A comprehensive literature search was conducted using PubMed and Google Scholar, with articles selected based on relevant keywords and evaluated for inclusion in this review. Conclusions: Effective management of PSC necessitates a multidisciplinary approach involving hepatologists, gastroenterologists, radiologists, and transplant surgeons. Ongoing efforts to better understand PSC’s pathogenesis, refine diagnostic methods, and develop more effective therapies are crucial for improving patient outcomes.

Cardiovascular diseases can be caused by numerous beginning conditions. The underpinning causes may include heart/ myocardial inflammation, cardio myopathy, coronary vascular complaint (CAD), dyslipidemia, hypertension, pulmonary hypertension, and arrhythmia, which may eventually affect heart and liver failure. The study was aimed to determine the efficacy, usage and adverse effects of furosemide in diseased heart conditions. Furosemide is prescribed in the treatment of various cardiovascular illnesses, including monitoring the effects in various age groups, gender and body weights. Considering all the primary parameters of drug dose and secondary parameters of dose duration and their certain categories, we evaluate the results based on the effectiveness of furosemide. The collected and gathered data is analyzed by the suitable statistical methods (Central tendency methods) like Arithmetic mean. The effectiveness of furosemide is rapid and strong in the age group of 39-69yrs with the sodium levels of 132.8mEq/L and the urine output of 2.23L/day. The drug shows potential adverse effects like Ototoxicity, skin irritations and stomach cramps, in people with existing heart conditions. The usage of furosemide is beneficial in heart patients however some people show some potential adverse effects. The drug poses its potential side effects only when the usage is high or in unauthorized dose and also depends on previously existed disease conditions.

Abstract Background Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. Methods From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan’s National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. Results The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. Conclusions This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

Background: Patients with angina are often suffering from comorbidities such as varying degrees of hepatic dysfunction. However, the impact of angina on the incidence of hepatic failure (HF) remains unclear. Methods: The genetic data were retrieved from genome-wide association studies. Five Mendelian randomization methods were used to investigate the causal relationship between unstable angina (UA), stable angina (SA), and HF. The result of the Inverse variance weighted (IVW) method was deemed the principal result. In addition, we performed a comprehensive sensitivity analysis to verify the robustness of the results. Results: The IVW results showed that UA (Odds ratio (OR): 2.055, 95% confidence interval (CI): 1.171–3.606, p = 0.012) was causally associated with the incidence of HF. SA (OR: 1.122, 95% CI: 0.738–1.706, p = 0.591) was not causally associated with the incidence of HF. Sensitivity analysis did not identify any bias in the results. Conclusions: UA turned out to be a risk factor for HF. SA does not have a significant causal effect on HF. Therefore, it is highly recommended that patients with chronic liver disease seek prompt medical attention and undergo regular monitoring of liver function when experiencing UA. This may help them to reduce the risk of HF. [ABSTRACT FROM AUTHOR]

Background: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. Methods: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. Results: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4–73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4–74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3–99.9%). Conclusion: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. Methods: From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan's National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. Results: The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. Conclusions: This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results. [ABSTRACT FROM AUTHOR]

The liver is known to possess remarkable regenerative potential, but persistent inflammation or severe acute injury can lead to liver fibrosis and incomplete regeneration, ultimately resulting in liver failure. Recent studies have shown that the axis of two types of CXCL12 receptors, CXCR4 and CXCR7, plays a crucial role in liver fibrosis and regeneration. The present study aimed to investigate the regulatory factors involved in CXCR4 expression in injured liver. Immunohistochemical screening of liver tissue samples collected during liver transplantation revealed a reciprocal expression pattern between CXCR4 and MeCP2. An in vitro system involving cultured cell lines and H2O2 treatment was established to study the impact of oxidative stress on signaling pathways and epigenetic alterations that affect CXCR4 mRNA expression. Operating through distinct signaling pathways, H2O2 treatment induced a dose-dependent increase in CXCR4 expression in both hepatocyte- and intrahepatic cholangiocyte-derived cells. Treatment of the cells with trichostatin and azacytidine modulated CXCR4 expression in hepatocytes by modifying the methylation status of CpG dinucleotides located in a pair of TA repeats adjacent to the TATA box of the CXCR4 gene promoter. Only MeCP2 bound to oligonucleotides representing the TATA box region when the cytosine residues within the sequence were methylated, as revealed by electrophoretic mobility shift assay (EMSA). Methylation-specific PCR analysis of microdissected samples revealed a correlation between the loss of CpG methylation and the upregulation of CXCR4 in injured hepatocytes, replicating the findings from the in vitro study. Besides the conventional MEK/ERK and NF-κB signaling pathways that activate CXCR4 in intrahepatic cholangiocytes, the unique epigenetic modifications observed in hepatocytes might also contribute to a shift in the CXCR4–CXCR7 balance towards CXCR4, leading to irreversible liver injury and fibrosis. This study highlights the importance of epigenetic modifications in regulating CXCR4 expression in liver injury and fibrosis. [ABSTRACT FROM AUTHOR]

Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24–72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [18F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [18F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUVav) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [18F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUVav compared to controls (p = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [18F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET’s potential as a non-invasive imaging biomarker for early-stage ALF.

Background: Dengue, is an arthropod-borne viral disease of significant public health importance. In the context of the rising burden of Dengue in South Odisha, this hospital-based cross-sectional study conducted at MKCG Medical College Hospital, Berhampur, aims to evaluate liver function tests in 100 Dengue patients. Recognizing the significance of hepatic involvement in Dengue, the study seeks to contribute valuable insights into the hepatic manifestations of the disease, potentially enhancing diagnostic and management strategies in this region. Methodology: Utilizing a systematic approach, this study employed a cross-sectional design at MKCG Medical College Hospital, Berhampur, enrolling 100 Dengue patients. Standardized liver function tests were conducted, including serum bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase. Data analysis involved descriptive statistics, providing a comprehensive overview of hepatic parameters in Dengue patients within the specified tertiary care setting Results: Among 100 Dengue patients, 40% exhibited less than a 2-fold increase in AST levels, while 28% showed a 2-10-fold rise, and 10% demonstrated more than a 10-fold increase. Overall, 22% maintained normal SGOT values, with 78% displaying elevated levels. Regarding SGPT, 20% had normal values, 35% presented with less than a 2-fold increase, 25% displayed a 2-10-fold rise, and 20% had more than a 10- fold increase from normal levels. Early-stage symptoms like vomiting and abdominal pain correlated with hepatic involvement, with statistically higher AST and ALT levels in patients developing complications such as DHF, DSS, hepatic failure, ARDS, AKI, and encephalopathy Conclusion: In summary, our study reveals a notable prevalence of hepatic involvement in Dengue patients, emphasizing the significance of vigilant monitoring, particularly in cases with early symptoms and those at risk of complications. These findings offer crucial insights for tailored interventions and enhanced patient care within the tertiary care context of South Odisha. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Despite improvements in the management of chronic hepatitis B (CHB), risk of cirrhosis and hepatocellular carcinoma remains. While hepatitis B surface antigen loss is the optimal end point, safe discontinuation of nucleos(t)ide analog (NA) therapyis controversial because of the possibility of severe or fatal reactivation flares. METHODS: This is a multicenter cohort study of virally suppressed, end-of-therapy (EOT) hepatitis B e antigen (HBeAg)-negative CHB patients who stopped NA therapy (n 5 1,557). Survival analysis techniques were used to analyze off-therapy rates of hepatic decompensation and differences by patient characteristics. We also examined a subgroup of noncirrhotic patients with consolidation therapy of ≥12 months before cessation (n 5 1,289). Hepatic decompensation was considered related to therapy cessation if diagnosed off therapy or within 6 months of starting retreatment. RESULTS: Among the total cohort (11.8% diagnosed with cirrhosis, 84.2% start-of-therapy HBeAg-negative), 20 developed hepatic decompensation after NA cessation; 10 events were among the subgroup. The cumulative incidence of hepatic decompensation at 60 months off therapy among the total cohort and subgroup was 1.8% and 1.1%, respectively. The hepatic decompensation rate was higher among patients with cirrhosis (hazard ratio [HR] 5.08, P < 0.001) and start-of-therapy HBeAg-positive patients (HR 5.23, P < 0.001). This association between start-of-therapy HBeAg status and hepatic decompensation remained significant even among the subgroup (HR 10.5, P < 0.001). DISCUSSION: Patients with cirrhosis and start-of-therapy HBeAg-positive patients should be carefully assessed before stopping NAs to prevent hepatic decompensation. Frequent monitoring of viral and host kinetics after cessation is crucial to determine patient outcome. [ABSTRACT FROM AUTHOR]

'Drug Induced Hypersensitivity Syndrome' (DiHS) or 'Drug Rash with Eosinophilia and Systemic Symptoms' (DRESS) syndrome is a life threatening, delayed type drug hypersensitivity reaction. This syndrome is characterized by fever, skin rash, lymphadenopathy, hematological abnormalities and visceral involvement and liver is the most frequently involved visceral organ. Liver involvement is mostly presented as acute anicteric hepatitis with elevated liver enzymes. Rarely, it can be presented as cholestasis which indicates a worse prognosis. In this article, a case of valproic acid induced- DRESS syndrome who presented with acute hepatic failure is presented. Diagnosis of DRESS syndrome may delay due to the long interval between drug intake and the onset of symptoms. The variety of symptoms can also be challenging. Early diagnosis is important in terms of reducing morbidity and mortality. [ABSTRACT FROM AUTHOR]

The liver is a major organ with multiple functions. A number of drugs are metabolized by the liver during phase 1 and 2 reactions which include complex processes involving cytochrome P450 enzymes. Genetic and acquired variability in cytochrome P450 activity may have profound effects on pharmacokinetics. Additionally, drugs can also modify how the liver functions and cause dysfunction or even failure of the organ both by a direct effect on the liver or by alteration in liver blood flow. It is important to recognize the signs and symptoms of liver failure in patients and identify possible causes including drug interactions. Furthermore, once a patient has been recognized to be suffering with liver dysfunction or failure drug choice and dosing regime will need to be rationalized. Paracetamol overdose can have severe and life-threatening consequences for patients due to its effect on liver function. It is the leading cause of acute liver failure in the UK,1 Correct and early management is crucial and will be discussed within this article. [ABSTRACT FROM AUTHOR]

Background: Liver transplant is the only cure for cirrhosis. We studied the impact of palliative care on patient care by conducting a population-based cohort study. Methods: We queried the Explorys database (IBM, New York) database for a diagnosis of 'cirrhosis' followed by 'palliative care consultation' and collected demographic and clinical data. Results: We identified 316,970 patients with cirrhosis. Palliative care was consulted for 10.9% (n = 34,600) of patients. Patients aged >65 [OR 1.33 (1.30-1.36), P <.0001], men [OR 1.13 (1.11-1.16), P <.0001], a diagnosis of hepatocellular carcinoma (HCC) [OR 2.53 (2.45-2.60), P <.0001] were more likely to receive a palliative care consultation. Patients for whom palliative care were consulted were less likely to undergo surgical procedures [OR.49 (.47-.50)]. Conclusion: Only about 1 in 10 cirrhotics received a palliative care consultation. Older patients, males, and patients with a diagnosis of HCC are more likely to receive palliative care. [ABSTRACT FROM AUTHOR]

Introduction:Hepatic encephalopathy (HE) is a common complication of acute and chronic liver failure, which can lead to significant morbidity and mortality. Grade 3-4 HE patients are typically managed with routine intubation and mechanical ventilation. However, recent research suggests that routine intubation may increase the risk of complications and death for the preservation of the airway. This study investigated the use of non-invasive ventilation (NIV) in patients with grade 3 encephalopathy associated with acute and chronic liver failure.Methods:This retrospective study included patients with grade 3 encephalopathy associated with liver failure who underwent NIV between January 2022 and March 2023 in a liver transplant intensive care unit. The patient demographic data, laboratory results, comorbidities, and outcomes were collected and analyzed. The results were compared to those of HE patients who were intubated as reported in the literature.Results:A total of 41 children and adults with grade 3 HE who received NIV were included in this study. Compared with HE patients who were intubated as reported in the literature, the NIV group had significantly lower rates of complications and mortality. Additionally, there were no additional complications observed in patients who received NIV without intubation, such as infections, cardiovascular disorders, or cognitive impairments.Conclusion:The use of NIV in grade 3 HE patients suggests that it is an effective alternative to intubation. These findings support the need for careful consideration when deciding to intubate HE patients and suggest that continuous support using NIV may provide potential benefits. Further studies are needed to investigate the optimal management of these patients to improve their outcomes.

Abstract Background Hepatic failure induced by immune checkpoint inhibitors (ICIs) has been reported in only a few case series and case reports. Objective We aimed to explore the association between ICIs and hepatic failure and characterize the clinical features of ICI‐associated hepatic failure in the pharmacovigilance database. Methods Data from the first quarter (Q1) of 2015 to the fourth quarter (Q4) of 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality and Bayesian analysis. Reporting odds ratios (ROR) and information component (IC) were used to evaluate correlations between ICIs and hepatic failure. Results Hepatic failure occurred in 0.19% (18,454/9,647,655) of all cases in the FAERS database, of which 654 cases were associated with ICIs. The overall median time from ICIs initiation to hepatic failure onset was 38 days, 72.3% of the adverse events occurred within the first 3 months, and 68.65% of the cases died after developing hepatic failure. In general, a strong signal was shown between ICIs and hepatic failure (ROR025 = 2.70, IC025 = 1.39). For the three categories of ICIs, programmed cell death 1 ligand 1 inhibitors (ROR025 = 3.09, IC025 = 1.57) had a higher risk signal than programmed cell death protein 1 inhibitors and cytotoxic T lymphocyte‐associated protein 4 inhibitors. For monotherapy, atezolizumab showed the strongest risk signal (ROR025 = 4.07, IC025 = 1.90). The combination of nivolumab and ipilimumab showed stronger signals of hepatic failure compared with nivolumab or ipilimumab alone (nivolumab + ipilimumab vs. ipilimumab: ROR025 = 1.40, IC025 = 0.16; nivolumab + ipilimumab vs. nivolumab: ROR025 = 1.24, IC025 = 0.34). Considering the concomitant agents used with ICIs, the majority of these regimens showed stronger signals than ICI monotherapy, such as acetaminophen (ICIs + acetaminophen vs. ICIs: ROR025 = 1.06, IC025 = 0.32). Conclusions ICIs had possible strong signals associated with hepatic failure, and most cases of hepatic failure occurred within the first 3 months and had poor outcomes, which should attract clinical attention.

Nivolumab is a promising monoclonal antibody inhibitor of programmed death-1, a protein on the surface of T-cells. As such, it is approved for use in patients with multiple advanced malignancies and can significantly elongate progression-free survival. However, monoclonal antibody inhibitors can lead to adverse hepatic reactions, which in rare cases result in further hepatic damage. Herein, we present a case of a patient with locally advanced gastric carcinoma treated with fluorouracil, oxaliplatin, docetaxel and the checkpoint inhibitor nivolumab. Five months after her first dosage of nivolumab and without a preexisting liver disease, she presented with transaminitis. During the course of her stay, the patient developed status epilepticus, which required mechanical ventilation followed by fulminant hepatic failure. A subsequent liver biopsy revealed severe liver damage with extensive confluent parenchymal necrosis corresponding to checkpoint-inhibitor-induced hepatitis. Alternative reasons for this hepatic failure were ruled out. Despite aggressive therapeutic interventions including corticosteroids and plasma exchange, the patient died due to liver failure. Although hepatic failure is rarely seen in patients with checkpoint inhibitor therapy, it requires early awareness and rapid intervention. [ABSTRACT FROM AUTHOR]

Background and Aim: Alcohol‐associated hepatitis (AAH) is an acute, inflammatory liver disease with severe short‐term and long‐term morbidity and mortality. AAH can lead to severe complications including hepatic failure, gastrointestinal bleeding, sepsis, and the development or decompensation of cirrhosis. Rifaximin is an antibiotic that reduces bacterial overgrowth and gut translocation, and it may have a role in decreasing systemic inflammation and infection in patients with AAH. Therefore, we conducted a systematic review and meta‐analysis to evaluate the role of rifaximin in the management of AAH. Methods: A comprehensive search strategy was used to identify studies that met our inclusion criteria in Embase, MEDLINE (PubMed), Cochrane Library, Web of Science Core Collection, and Google Scholar. Outcomes of interest included rates of infection, 90‐day mortality, and overall mortality between the rifaximin versus non‐rifaximin group. Open Meta Analyst software was used to compute the results. Results: Three studies with a total of 162 patients were included in the final meta‐analysis. Of the three studies, two were randomized control trials (RCTs), and one was a case–control study. There was a significantly lower rate of infection in the rifaximin group versus the non‐rifaximin group (RR: 0.331, 95% CI: 0.159–0.689, I2 = 0%, P = 0.003). There was no significant difference in 90‐day mortality in the rifaximin versus non‐rifaximin group (RR: 0.743, 95% CI: 0.298–1.850, I2 = 24%, P = 0.523), nor was there a significant difference in overall mortality (RR: 0.624, 95% 95% CI: 0.299–1.3, I2 = 7.1%, P = 0.208). Conclusions: The use of rifaximin in AAH is associated with a lower rate of infection rate than the non‐rifaximin group. Additional research is needed to determine whether this effect is more pronounced in patients concurrently being treated with prednisolone. Differences in 90‐day or overall mortality did not reach statistical significance. Further studies, particularly large randomized controlled trials, are needed to establish the role of rifaximin in AAH, especially as an adjunct therapy with prednisolone. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is a common pediatric malignancy, typically manifesting with symptoms of bone marrow and hematolymphoid organ infiltration. Although hepatic involvement in the form of hepatosplenomegaly is seen in nearly two-thirds of the patients, primary presentation as acute liver failure is rare. Clinical Description: A 12-year-old boy presented with complaints of abdominal distention with jaundice for the past 15–20 days, associated with transient fever of 6 days. Examination revealed pallor, icterus, and hepatosplenomegaly. A possibility of acute infectious or autoimmune hepatitis or hemolytic anemia was considered. Management: Liver function tests were deranged with hyperbilirubinemia with modest increase in transaminases and serum alkaline phosphatase along with deranged prothrombin time. The complete blood count showed pancytopenia with normal peripheral smear. Investigations for common infectious causes were noncontributory, as also those for autoimmune hepatitis. The direct Coombs test was also negative. In view of persistent pancytopenia with hyperbilirubinemia and hepatosplenomegaly, a bone marrow evaluation was done, which revealed B-cell ALL (B-ALL). Thus, the child was diagnosed with a case of ALL presenting with acute liver failure. The child was initially managed as a case of acute liver failure and on diagnostic confirmation, he was started on the B-ALL chemotherapy protocol as per his risk stratification with hepatic dose modification of chemotherapy. The child showed complete normalization of the liver functions by about 4 weeks of induction chemotherapy and achieved remission. Conclusions: A child presenting with acute liver failure may be having an underlying undiagnosed, clinically silent ALL. After ruling out common causes of acute liver failure, one must not forget the possibility of leukemic blast infiltration of the liver as a cause of liver failure. With early initiation of advanced chemotherapeutic induction regimens, there can be dramatic resolution of liver injury and remission of ALL.

Background: Hepatic failure induced by immune checkpoint inhibitors (ICIs) has been reported in only a few case series and case reports. Objective: We aimed to explore the association between ICIs and hepatic failure and characterize the clinical features of ICI‐associated hepatic failure in the pharmacovigilance database. Methods: Data from the first quarter (Q1) of 2015 to the fourth quarter (Q4) of 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved for disproportionality and Bayesian analysis. Reporting odds ratios (ROR) and information component (IC) were used to evaluate correlations between ICIs and hepatic failure. Results: Hepatic failure occurred in 0.19% (18,454/9,647,655) of all cases in the FAERS database, of which 654 cases were associated with ICIs. The overall median time from ICIs initiation to hepatic failure onset was 38 days, 72.3% of the adverse events occurred within the first 3 months, and 68.65% of the cases died after developing hepatic failure. In general, a strong signal was shown between ICIs and hepatic failure (ROR025 = 2.70, IC025 = 1.39). For the three categories of ICIs, programmed cell death 1 ligand 1 inhibitors (ROR025 = 3.09, IC025 = 1.57) had a higher risk signal than programmed cell death protein 1 inhibitors and cytotoxic T lymphocyte‐associated protein 4 inhibitors. For monotherapy, atezolizumab showed the strongest risk signal (ROR025 = 4.07, IC025 = 1.90). The combination of nivolumab and ipilimumab showed stronger signals of hepatic failure compared with nivolumab or ipilimumab alone (nivolumab + ipilimumab vs. ipilimumab: ROR025 = 1.40, IC025 = 0.16; nivolumab + ipilimumab vs. nivolumab: ROR025 = 1.24, IC025 = 0.34). Considering the concomitant agents used with ICIs, the majority of these regimens showed stronger signals than ICI monotherapy, such as acetaminophen (ICIs + acetaminophen vs. ICIs: ROR025 = 1.06, IC025 = 0.32). Conclusions: ICIs had possible strong signals associated with hepatic failure, and most cases of hepatic failure occurred within the first 3 months and had poor outcomes, which should attract clinical attention. [ABSTRACT FROM AUTHOR]

BackgroundWe describe three cases involving three patients with PRETEXT III hepatoblastoma invading the hepatic hilum. After portal vein embolization, the patients underwent uncomplicated trisectionectomy.MethodsMedical records between March 2016 and March 2021 were reviewed, and three patients were selected. A literature review of techniques for increasing future liver remnant in children diagnosed with hepatoblastoma was also conducted.ResultsAll tumors involved the right lobe and hepatic hilum (PRETEXT III). After neoadjuvant chemotherapy, the tumor size decreased, but hilar involvement was unimproved. Right portal vein ligation (RPVL) was performed to increase the left lobe volume. Post-ligation, the remnant liver increased. Liver function was restored to normal levels within 5 days after the hepatectomy. All patients underwent two cycles of adjuvant chemotherapy without tumor recurrence.ConclusionsRPVL can be safely performed before extended hepatic resection in children with a giant hepatoblastoma invading the hepatic hilum. The tumor was completely resected by securing a sufficient margin and increasing the residual liver volume with portal vein embolization. The patients recovered and underwent adjuvant chemotherapy without the deterioration of liver function.

Introduction: Hepatic encephalopathy (HE) is a common complication of acute and chronic liver failure, which can lead to significant morbidity and mortality. Grade 3-4 HE patients are typically managed with routine intubation and mechanical ventilation. However, recent research suggests that routine intubation may increase the risk of complications and death for the preservation of the airway. This study investigated the use of non-invasive ventilation (NIV) in patients with grade 3 encephalopathy associated with acute and chronic liver failure. Methods: This retrospective study included patients with grade 3 encephalopathy associated with liver failure who underwent NIV between January 2022 and March 2023 in a liver transplant intensive care unit. The patient demographic data, laboratory results, comorbidities, and outcomes were collected and analyzed. The results were compared to those of HE patients who were intubated as reported in the literature. Results: A total of 41 children and adults with grade 3 HE who received NIV were included in this study. Compared with HE patients who were intubated as reported in the literature, the NIV group had significantly lower rates of complications and mortality. Additionally, there were no additional complications observed in patients who received NIV without intubation, such as infections, cardiovascular disorders, or cognitive impairments. Conclusion: The use of NIV in grade 3 HE patients suggests that it is an effective alternative to intubation. These findings support the need for careful consideration when deciding to intubate HE patients and suggest that continuous support using NIV may provide potential benefits. Further studies are needed to investigate the optimal management of these patients to improve their outcomes. [ABSTRACT FROM AUTHOR]

Background: Adequate management of diabetes in patients with liver cirrhosis can be challenging. We conducted this study to investigate the liver-related long term outcomes of alpha-glucosidase inhibitors (AGIs) in patients with diabetes and cirrhosis. Methods: From National Health Insurance Research Database (NHIRD) in Taiwan, we recruited propensity-score matched alpha-glucosidase inhibitor users and non-users from a cohort of type 2 diabetes mellitus (T2DM) with compensated liver cirrhosis between 1 January 2000, and 31 December 2017, and followed them until 31 December 2018. Cox proportional hazards models with robust sandwich standard error estimates were used to assess the risk of main outcomes for alpha-glucosidase inhibitor users versus non-users. Results: The incidence rates of mortality during follow-up were 65.56 vs. 96.06 per 1,000 patient-years for alpha-glucosidase inhibitor users and non-users, respectively. The multivariable-adjusted model shows that alpha-glucosidase inhibitor users had significantly lower risks of all-cause mortality (aHR 0.63, 95% CI 0.56–0.71), hepatocellular carcinoma (aHR 0.55, 95% CI 0.46–0.67), decompensated cirrhosis (aHR 0.74 95% CI 0.63–0.87), hepatic encephalopathy (aHR 0.72, 95% CI 0.60–0.87), and hepatic failure (aHR 0.74, 95% CI 0.62–0.88) than alpha-glucosidase inhibitor non-users. Patients who received alpha-glucosidase inhibitors for a cumulative duration of more than 364 days had significantly lower risks of these outcomes than non-users. Conclusion: Alpha-glucosidase inhibitor use was associated with a lower risk of mortality, hepatocellular carcinoma, decompensated cirrhosis, and hepatic failure in patients with diabetes and compensated cirrhosis. alpha-glucosidase inhibitors may be useful for the management of diabetes in patients with compensated liver cirrhosis. Large-scale prospective studies are required to verify our results. [ABSTRACT FROM AUTHOR]

Since excessive alcohol consumption is a shared risk factor for esophageal cancer and liver fibrosis, it is possible that patients with esophageal cancer may develop unknown liver fibrosis or cirrhosis. We applied preoperative transient elastography (TE) to patients without recorded cirrhosis undergoing esophagectomy to clarify the validity in predicting postesophagectomy hepatic failure. The cohort consisted of 107 patients who received TE before esophagectomy between June 2018 and December 2021. Patients were categorized into two groups based on the fibrosis score yielded by preoperative TE (mild group: 0~2, n = 92; severe group: 3~4, n = 15). There was no significant difference in demographic data nor surgical variables between the two groups. None of the cohort encountered hepatic failure, yet the severe fibrosis group had a significantly higher rate of pleural effusion (40.0% versus 15.2%, p = 0.03). The areas under the curve (AUCs) of TE in predicting postoperative complications and 180-day mortality were 0.60 (95% CI: 0.46–0.74) and 0.67 (95% CI: 0.51–0.83), respectively. In conclusion, stratification of patients with esophageal cancer who had liver fibrosis by preoperative TE demonstrates significant validity in predicting postoperative pleural effusions. Recruitment of noncirrhotic patients with higher TE scores is warranted to examine its power in other parameters. [ABSTRACT FROM AUTHOR]

Background: Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome, is a rare autosomal recessive disorder characterized by impaired ornithine transport across the inner mitochondrial membrane. HHH is caused by biallelic disease-causing variants in the SLC25A15 gene. The clinical presentation of HHH is highly variable ranging from severe neonatal encephalopathy and hepatic failure to a milder form with corresponding learning difficulties. Methods: In this study, data from thirteen patients with HHH syndrome, diagnosed between the age of 1 week-29 years at two tertiary care centers in Palestine, is presented. The clinical, biochemical, and molecular data are reviewed. Results: Analysis of the SLC25A15 gene sequence revealed a novel homozygous frameshift deletion in exon 5, NM_014252.4:c.552-555delTTTC; p (Phe185SerfsTer8) in nine patients. The remaining four patients had a recurrent homozygous frameshift variant; NM_014252.4: c.446delG, (p.Ser149ThrfsTer45). The major acute clinical presentation found was encephalopathy and liver dysfunction. Nervous system involvement was common, progressive, and presented with signs of upper motor neuron disease as well as variable degrees of cognitive impairment. One patient had an initial presentation in adulthood with acute encephalopathy that responded well to treatment. There was no clear genotype-phenotype correlation. Conclusion: Our results confirm the marked clinical heterogeneity of HHH including severe neonatal presentation, hepatic failure, and progressive pyramidal tract dysfunction in all age groups. The disease progression was variable, even in patients with the same genetic variant, and in patients with severe neonatal-onset hepatic encephalopathy. We report a novel pathogenic variant in the SLC25A15 gene, further expanding the molecular spectrum of the disease. [ABSTRACT FROM AUTHOR]

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) is a lethal complication. We present the case of a patient who underwent salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft because of HAT following LDLT. A 64-year-old female patient diagnosed with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma underwent salvage LDLT using a modified right liver graft. Partial graft infarct was identified at posttransplant day 4, and by day 9, it had spread. Celiac arteriography showed complete occlusion of the graft hepatic artery. We performed redo hepatic artery reconstruction using a fresh iliofemoral artery homograft 10 days after the LDLT operation because such a vessel homograft was available at our institutional tissue bank. The infrarenal aorta was dissected and an iliofemoral artery graft was anastomosed. Soon after hepatic artery revascularization, liver function progressively improved, and the infarct area at the liver graft was reduced. The patient has been doing well for 10 years without any vascular complications. In conclusion, our experience with this case suggests that salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft is a feasible option to treat HAT following LDLT, as in deceased donor liver transplantation.

Background: Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome, is a rare autosomal recessive disorder characterized by impaired ornithine transport across the inner mitochondrial membrane. HHH is caused by biallelic disease-causing variants in the SLC25A15 gene. The clinical presentation of HHH is highly variable ranging from severe neonatal encephalopathy and hepatic failure to a milder form with corresponding learning difficulties.Methods: In this study, data from thirteen patients with HHH syndrome, diagnosed between the age of 1 week–29 years at two tertiary care centers in Palestine, is presented. The clinical, biochemical, and molecular data are reviewed.Results: Analysis of the SLC25A15 gene sequence revealed a novel homozygous frameshift deletion in exon 5, NM_014252.4:c.552-555delTTTC; p (Phe185SerfsTer8) in nine patients. The remaining four patients had a recurrent homozygous frameshift variant; NM_014252.4:c.446delG, (p.Ser149ThrfsTer45). The major acute clinical presentation found was encephalopathy and liver dysfunction. Nervous system involvement was common, progressive, and presented with signs of upper motor neuron disease as well as variable degrees of cognitive impairment. One patient had an initial presentation in adulthood with acute encephalopathy that responded well to treatment. There was no clear genotype-phenotype correlation.Conclusion: Our results confirm the marked clinical heterogeneity of HHH including severe neonatal presentation, hepatic failure, and progressive pyramidal tract dysfunction in all age groups. The disease progression was variable, even in patients with the same genetic variant, and in patients with severe neonatal-onset hepatic encephalopathy. We report a novel pathogenic variant in the SLC25A15 gene, further expanding the molecular spectrum of the disease.

Background and aims: Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). Methods: Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). Results: Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age—46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27–40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age—44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24–40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00–28.00] vs. 17.00 [15.00–21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03–9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2–2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1–2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. Conclusion: Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF. [ABSTRACT FROM AUTHOR]

Breast cancer with liver metastasis (BCLM) frequently cause hepatic failure owing to extensive liver metastasis compared to other cancers; however, there are no clinicopathologic or radiologic parameters for estimating BCLM prognosis. We analyzed the relationship between radiologic and clinicopathologic characteristics with survival outcomes in BCLM. During 2009–2019, baseline and final abdomen computed tomography or liver magnetic resonance imaging of BCLM patients were reviewed. Liver metastasis patterns were classified as oligometastasis (≤3 metastatic lesions), non-confluent or confluent mass formation, infiltration, and pseudocirrhosis. Thirty-one surgical or biopsy specimens for liver metastasis were immunostained for L1 adhesion molecule (L1CAM), Yes-associated protein 1/Transcriptional co-activator with PDZ-binding motif (YAP/TAZ), and β1-integrin. Out of 156 patients, 77 initially had oligometastasis, 58 had nonconfluent mass formation, 14 had confluent mass formation, and 7 had infiltrative liver metastasis. Confluent or infiltrative liver metastasis showed inferior liver metastasis-associated survival (LMOS) compared to others (p = 0.001). Positive staining for L1CAM and YAP/TAZ was associated with inferior survival, and YAP/TAZ was related to final liver metastasis. Initial hepatic metastasis was associated with LMOS, especially confluent mass formation, and infiltrative liver metastasis pattern was associated with poor survival. Positive staining for YAP/TAZ and L1CAM was associated with inferior LMOS, and YAP/TAZ was related to final liver metastasis. [ABSTRACT FROM AUTHOR]

Background: Depending on the genetic mutation, mitochondrial hepatopathy has a variable presentation. Spontaneous recovery is a rare occurrence in these patients. However, complete recovery is possible in infants having t-RNA5-methylaminomethyl-2-thiouridylate methyl-transferase (TRMU) gene mutation. Case presentation: A 53-day-old female child presented with hepatopathy and lactic acidosis. Genetic work up showed she has a mitochondrial respiratory chain disorder due to the TRMU gene mutation. Very few patients with isolated hepatic involvement have been described in the literature. We are reporting the first case from India of transient hepatopathy due to heterozygous TRMU gene mutation. Recovery was spontaneous at 4 months of age. Conclusion: Complete recovery is possible in infants having TRMU mutation if they are supported through and survive the acute phase. The identification of TRMU mutation could impact clinical management. [JBCGenetics 2021; 4(1.000): 64-67]

Abstract Background Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis. Methods From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan’s National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes. Results The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18–1.45), 1.18 (1.05–1.34), 1.53 (1.35–1.72), 1.26 (1.42–1.86), 1.41 (1.23–1.62), and 3.33 (2.45–4.53), respectively. Conclusions This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.

Cerebral arteriovenous malformations (cAVMs) are traditionally considered congenital anomalies. The literature includes only two reported cases of de novo solitary cAVMs associated with liver cirrhosis (LC). Here, we report a unique case of multiple de novo cAVMs in a patient with alcoholic LC. Teaching point: In patients with potential risks for de novo cAVM, including liver cirrhosis, the possibility of multiple de novo cAVMs should be considered.

Introduction: Upper gastrointestinal bleeding of variceal origin has a high mortality. The platelet count/spleen major diameter ratio may be a useful noninvasive parameter to predict esophageal variceal bleeding in cirrhotic patients. Objective: to determine the sensitivity and specificity of the platelet count/spleen diameter ratio for the diagnosis of esophageal varices with risk of bleeding in patients with hepatic insufficiency. Material and Methods: Process study, performed in a Second Level Medical Facility, in patients with liver failure who underwent ultrasound, blood cytometry, liver function tests and endoscopy. Sensitivity and specificity of the platelet/spleen ratio were assessed in patients with esophageal variceal and bleeding risk. Results: There were 70 patients: 28 women, 42 men; main cause of liver failure in men was ethylism in 31 patients and hepatitis C virus in 20 women. The spleen-platelet ratio has a sensitivity of 90%, specificity 83%, false positives 16%, false negatives 9%, positive predictive value 94%, negative predictive value 75%, prevalence of 74% and diagnostic accuracy of 88% to diagnose esophageal varices with risk of bleeding. Conclusion: Platelet/spleen ratio is a useful, non-invasive study to diagnose esophageal varices with bleeding risk, in hospitals where endoscopy is not available.

Introduction: Hodgkin lymphoma is a highly curable lymphoproliferative malignancy with an overall relative survival rate of 87.4%. It is characterized by multinucleated Reed–Sternberg cells which are mostly derived from B cells in the germinal center. Case report: We present a case of a 40-year-old gentleman with acquired immunodeficiency syndrome who presented with Stage 4b Hodgkin lymphoma complicated with fulminant hepatic failure and direct hyperbilirubinemia. The initial presentation of Hodgkin lymphoma as cholestatic jaundice is extremely rare. Management and outcome: Though the survival rate with chemotherapy is high, the fulminant hepatic failure made the situation challenging with the use of chemotherapeutic regimens that require hepatic excretion. He received dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen [doxorubicin 12.5 mg (6.75 mg/m2), bleomycin 18 units (10 units/m2), vinblastine 3 mg (1.5 mg/m2), dacarbazine 380 mg (190 mg/m2)] as well as bictegravir/emtricitabine/tenofovir alafenamide since admission for treatment of human immunodeficiency virus and hepatitis B. He started responding with the first cycle of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen with bilirubin levels trended down and normalized as well as his clinical condition improved. He received the full dose of adriamycin-bleomycin-vinblastine-dacarbazine on day 15. Discussion: Our case report emphasizes that the early usage of dose reduced adriamycin-bleomycin-vinblastine-dacarbazine regimen can restore hepatic function and can achieve improvement in hepatic function allowing the delivery of full-dose chemotherapy. [ABSTRACT FROM AUTHOR]

Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure. [ABSTRACT FROM AUTHOR]