Worsening Liver Function Research Articles

Changes in interoception before and after treatment in patients with alcohol use disorder.

To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception. The Body Perception Questionnaire-Body Awareness ultra-short version Japanese version (BPQ-BAVSF-J) was used to measure interoception in 50 alcohol-dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ-BAVSF-J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), mean corpuscular volume, platelet count, and Fib-4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group. The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ-BAVSF-J and Fib-4 index and AST. The BPQ-BAVSF-J score significantly decreased at discharge in the inpatient group. AST, ALT, γ-GTP, and Fib-4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ-BAVSF-J score, AST level, ALT level, γ-GTP level, and Fib-4 index between at the first outpatient visit and approximately 3 months after the visit. Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ-BAVSF-J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration.

Predictors of Hepatic Decompensation after Yttrium90 Transarterial Radioembolization—Optimizing Patient Selection

Abstract Purpose Yttrium 90 (Y90) transarterial radioembolization (TARE) is effective for unresectable hepatocellular carcinoma (HCC) or to bridge/downstage before transplant; however, optimal patient selection is not well-described. This study aims to identify factors that increase risk of liver decompensation resulting in hospital admissions after TARE. Methods Patients who received Y90 as their first treatment during 2012 to 2022 were identified from a prospectively collected database of 1675 HCC patients. Clinically significant hepatic decompensation was defined as total bilirubin more than or equal to 3 mg/dL or any increase in Model for End-stage Liver Disease (MELD) score resulting in readmission within 60 days or death. Results Of 137 patients, 7 (5.1%) developed hepatic decompensation requiring admission within 30 days and an additional 8 (10.9%) within 60 days. Two of these patients (1.4%) died and two (1.4%) required urgent transplant within 2 months. Preprocedure albumin less than 3.5 gm/dL (p = 0.0207), international normalized ratio more than 1.2 (p = 0.017), ascites (p = 0.036), elevated MELD (p = 0.012), and Child-Pugh (p = 0.007) scores were significant predictors of decompensation, while creatinine and sodium were not. Patients with Child-Pugh B score were three to four times more likely to decompensate (28 vs. 8%) compared to Child-Pugh A. For every unit increase in Child-Pugh score more than 6, odds of decompensation increased by a factor of 2.15. Conclusion Y90 TARE is safe and effective; however, 10.9% patients require readmission for worsened liver function. Because ascites is a significant factor in predicting decompensation and all patients require adequate renal function to receive Y90 TARE, Child-Pugh score may be more useful than MELD for patient selection. Further risk stratification may be required for those with a Child-Pugh score more than or equal to 7.

Heterogeneity of macrophage activation syndrome and treatment progression.

Macrophage activation syndrome (MAS) is a rare complication of autoimmune inflammatory rheumatic diseases (AIIRD) characterized by a progressive and life-threatening condition with features including cytokine storm and hemophagocytosis. Predisposing factors are typically associated with microbial infections, genetic factors (distinct from typical genetically related hemophagocytic lymphohistiocytosis (HLH)), and inappropriate immune system overactivation. Clinical features include unremitting fever, generalized rash, hepatosplenomegaly, lymphadenopathy, anemia, worsening liver function, and neurological involvement. MAS can occur in various AIIRDs, including but not limited to systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), systemic lupus erythematosus (SLE), Kawasaki disease (KD), juvenile dermatomyositis (JDM), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), etc. Although progress has been made in understanding the pathogenesis and treatment of MAS, it is important to recognize the differences between different diseases and the various treatment options available. This article summarizes the cell types and cytokines involved in MAS-related diseases, the heterogeneity, and treatment options, while also comparing it to genetically related HLH.

Intra-arterial PRRT with Lu-177 DOTATATE in Liver-dominant Metastatic Neuroendocrine Tumors: Early Assessment of Efficacy and Toxicity.

We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.

Steroid-responsive intractable pruritus in drug-induced liver injury: a case series

Background: Drug-induced liver injury (DILI) is commonly caused by modern medications, complementary and alternative medicines (CAMs), and other toxins. DILI is an umbrella term encompassing herb-induced liver injury (HILI) caused by herbs and CAMs, in addition to other medications. Apart from the cessation of the culprit drug and the supportive management, there are no definite treatment options for DILI. Although being used in DILI, steroids are not the standard medications for DILI, except that they are indicated for a few specific conditions. Materials and Methods: We report five cases of DILI with pruritus who responded well to steroids used as rescue therapy. DILI in these five cases was caused by CAMs (1), anabolic steroids (2), dapsone (1), and antifungal drug itraconazole (1). All patients presented with jaundice and pruritus, and their conditions did not improve following the discontinuation of offending agents and the implementation of supportive care. We used the Roussel UCLAF Causality Assessment Method 2016 for causality assessment. R-value was used to describe the pattern of liver injury. All patients underwent comprehensive work-up including liver biopsy as part of the procedure to rule out other potential etiologies. Steroids were used as a last resort, and both clinical and biochemical measurements were conducted. Results: The mean age of patients was 28.8 years, and the majority of them were males (80%). The median duration from symptom onset to presentation at our hospital was 4 weeks. The mean durations for pruritus improvement and complete biochemical improvement after steroid treatment were 3.2 weeks and 11.2 weeks, respectively. Extended follow-up was done for a mean period of 29.6 weeks from symptom presentation, and none of the patients had recurrence of liver injury after discontinuation of steroids. Conclusions: Ssteroids can be used to treat as rescue therapy for severe DILI with intractable pruritus in patients with worsening liver function. Relevance for Patients: DILI in selected cases can be therapeutically managed using steroids, which, however, should not be indicated as a first-line treatment.

Current Therapeutics in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gut-liver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC. Immunosuppressive and antifibrotic agents have not proven to be effective, but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics. Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid, or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials. In view of the enhanced malignancy risk, statins, and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients. For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function, balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.

Pre-transplant multidrug-resistant infections in liver transplant recipients-epidemiology and impact on transplantation outcome.

Cirrhotic patients are highly exposed to healthcare services and antibiotics. Although pre-liver transplantation (LT) infections are directly related to the worsening of liver function, the impact of these infections on LT outcomes is still unclear. This study aimed to identify the effect of multidrug-resistant microorganism (MDRO) infections before LT on survival after LT. Retrospective study that included patients who underwent LT between 2010 and 2019. Variables analyzed were related to patients' comorbidities, underlying diseases, time on the waiting list, antibiotic use, LT surgery, and occurrences post-LT. Multivariate analyses were performed using logistic regression, and Cox regression for survival analysis. A total of 865 patients were included; 351 infections were identified in 259 (30%) patients, of whom 75 (29%) had ≥1 pre-LT MDRO infection. The most common infection was spontaneous bacterial peritonitis (34%). The agent was identified in 249(71%), 53(15%) were polymicrobial. The most common microorganism was Klebsiella pneumoniae (18%); the most common MDRO was ESBL-producing Enterobacterales (16%), and carbapenem-resistant (CR) Enterobacterales (10%). Factors associated with MDRO infections before LT were previous use of therapeutic cephalosporin (p=.001) and fluoroquinolone (p=.001), SBP prophylaxis (p=.03), ACLF before LT (p=.03), and days of hospital stay pre-LT (p<.001); HCC diagnosis was protective (p=.01). Factors associated with 90-day mortality after LT were higher MELD on inclusion to the waiting list (p=.02), pre-LT MDRO infection (p=.04), dialysis after LT (p<.001), prolonged duration of LT surgery (p<.001), post-LT CR-Gram-negative bacteria infection (p<.001), and early retransplantation (p=.004). MDRO infections before LT have an important impact on survival after LT.

AST to Platelet Ratio Index (APRI), Fib-4 Score, and Pregnancy Outcome of Pregnant Women with Hepatitis B

Hepatitis B virus infection in pregnancy has become a major concern in many developing countries,. The relationship between hepatitis B virus infection and pregnancy is complex and puzzling. This study aimed to investigate the relationship between hepatitis B virus infection and pregnancy outcomes with the insights into the AST to Platelet Ratio Index (APRI) and Fib-4 score. This was a cross-sectional study on pregnant women with hepatitis B virus infections who underwent labor at dr. Zainal Abidin Hospital General Hospital, Aceh, Indonesia. Data were collected from the obstetric ward patient medical records from 2017 to 2019 and 77 pregnant women was identified to be infected with hepatitis B virus, of which 44 had complete medical record data and were included in the analysis. The median APRI in this study was 0.30 (0.1-1.2) while the median FIB-4 score was 0.74 (0.3-1.9). Delivery with live births was identified in 42 (95.5%) women. Term pregnancy and vaginal delivery were observed in 39 (88.6%) and 10 (22.7%) women, respectively, Complicated pregnancy was seen in 14 (31.8%) of pregnancies that included complications such as oligohydramnios, HELLP, severe preeclampsia, placenta previa, and premature rupture of membranes. APRI was higher in the stillbirth group (0.5 [0.2-0.8] p = 0.682) and preterm birth group (0.4 [0.2-0.6], p = 0.502). FIB-4 scores were higher in the stillbirth group (1.2 [0.5-1.8], p = 0.517) and preterm birth group (0.9 [0.4-1.9], p = 0.529). Hence, pregnancy does not always worsen liver function and is not related to the natural course of hepatitis B infection. Pregnancy with hepatitis B without fibrosis is not associated with poor pregnancy outcomes. Routine liver function examination is needed in pregnant mothers with hepatitis B virus infections.

EFFECT OF ALUMINIUM FLUORIDE ON LIVER FUNCTIONS OF RATTUSNORVEGICUS AFTER AMELIORATION BY MORINGA OLEIFERA

Animals and humans are frequently exposed to aluminium and fluoride, and poisoning can occur. Ingestion of aluminium-fluoride occurs primarily through inhalation of aerosols or particles, food, water and medication. This study addresses the serious effects of aluminum fluoride on liver function in albino rats (SGPT, SGOT and ALP) and their amelioration by Moringa oleifera. In this study, we selected 150 healthy adult male albino rats of almost same size and weight ((120 ± 25 gm) and eight weeks old)(because they have the same physiology as humans) and divided them into three groups (control group, treated-I with ALF and treated-II (ALF + Moringa). Rats were maintained on the diet selected according to diagnosis. According to the experimental protocol, rats were exposed to aluminum fluoride and Moringa. Biochemical studies of blood were performed according to standard methods and procedures. Significant changes in liver function (SGOT, SGPT and ALP) were observed in this study. The results showed that excessive aluminum fluoride intake worsened liver function, possibly due to the toxicity of aluminum fluoride. Aluminum fluoride induced liver dysfunction is mediated by increased oxidative stress in rats. Aluminum fluoride has a negative effect on blood sugar in albino rats. However, by including moringa in the treatment of albino rat, the negative effects of fluoride are reduced due to its healing effects. Keywords: Aluminium, Fluoride, Moringa oleifera, Albino Rat, SGPT, SGOT, ALP.

Transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma: A systematic review.

Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated. Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used. We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies. In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.

The possible role of Helicobacter pylori in liver diseases.

According to previous studies, Helicobacter pylori infection is associated with liver disease. In order to better understand the risk of acquiring various liver diseases, we reviewed current knowledge on the impact of H. pylori on the onset, intensification, and progression of various liver diseases caused by the infection of H. pylori. It has been estimated that between 50 and 90% of people worldwide have been infected with H. pylori. The bacterium is mostly responsible for inflamed gastric mucosa, ulcers, and cancers associated with the gastric mucosa. Through the active antioxidant system in H. pylori, the bacteria can neutralize free radicals by synthesizing VacA, a toxin that causes cell damage and apoptosis. Furthermore, there is a possibility that CagA genes may play a role in cancer development. People who have been infected with H. pylori are likely to develop lesions in the skin, the circulation system, and the pancreas. Moreover, transferring blood from the stomach may allow H. pylori to colonize the liver. The bacterium worsened liver function during autoimmune inflammation, toxic injury, chronic HCV infection, chronic HBV infection, and liver cirrhosis. Increasing portal pressure, hyperammonemia, and esophageal varices may be associated with H pylori infection. As a result, it is crucial to diagnose and treat this infection in patients with H. pylori.

P018 Non-alcoholic fatty liver disease in spondyloarthritis: identifying patients on therapy at high risk of serious liver disease

Abstract Background/Aims People with Spondyloarthritis (SpA), especially those with psoriatic disease (PsD) [psoriasis (PsO) and psoriatic arthritis (PsA)], are at higher risk of non-alcoholic fatty liver disease (NAFLD) due to increased prevalence of metabolic syndrome, obesity, hypertension, dyslipidaemia and disease-specific factors such as duration/ severity of psoriasis. There is significant concern that both synthetic and biological DMARDs (including methotrexate) may worsen liver function in PsD patients with NAFLD. The Leeds Teaching Hospitals Trust (LTHT) NAFLD pathway uses three screening tools (ELF, FIB-4 and fibroscanning) to identify those needing further investigation/ treatment by hepatology. However, the pathway is not validated in PsD. Our aim was to survey the prevalence of liver disease in our PsD population and explore the performance of our hepatology referral pathway. Methods We audited consecutive patients referred from the Leeds Specialist SpA service at LTHT with persistently abnormal ALT, whom the consultant Rheumatologist felt required Hepatology referral for suspected NAFLD. Data collected were: age, sex, BMI, history of diabetes, ALT, AST, platelets, albumin, hepatitis B and C, ELF score, FIB-4 score, fibroscan score, abdominal ultrasound, liver biopsy result and final hepatology diagnosis (NAFLD, fibrosis/cirrhosis or other). Results 72 patients were included; 84.2% had PsD (61/72), and 15.8% (11/62) had ‘Other’ forms of SpA (including axial spondyloarthritis, enteropathic arthritis, etc). Baseline characteristics, drug treatment and liver biochemistry/virology were similar between PsD and Other arthritis groups (Table 1) except for age which was lower in the Other. The average ELF scores were similar between PsD and Other, however FIB-4 scores were higher in PsD, and was associated with higher rates of fibrosis/cirrhosis (Table 1). FIB-4 &amp;gt;1.3, but not ELF&amp;gt;9.5, was statistically significantly associated with a high fibroscan score (p = 0.038 and p = 0.443 respectively). Conclusion PsD patients had higher rates of significant fibrosis/cirrhosis compared with patients with Other SpAs. FIB-4 was better than ELF for identifying which PsD patients required fibroscan and further investigation to exclude significant fibrosis/ cirrhosis. These findings will now be validated in a larger prospective study. Disclosure S.R. Harrison: None. U. Nandasoma: None. R. Parker: None. C. Chimakurthi: None. P. Laws: None. A. Barr: None. C. Vandevelde: None. H. Marzo-Ortega: None. J. Freeston: None.

Immune‐related adverse events in hepatitis treated with thiopurine‐based immunosuppressants: A case report

An 82-year-old man was treated with ipilimumab and nivolumab for malignant pleural mesothelioma. Although he was previously treated with prednisolone (1mg/kg/day) for immune-related adverse event (irAE) hepatitis by a previous doctor, he still had worsening liver function and was transferred to our hospital. Blood tests and imaging findings were negative for autoimmune and infectious hepatitis, and liver biopsy results were consistent with irAE hepatitis. Steroid pulse therapy improved liver function, but tapering to prednisolone (1mg/kg/day) again worsened his liver function. Concomitant use of mycophenolate mofetil was initiated, but no improvement in liver function was observed, therefore azathioprine, a thiopurine immunosuppressant, was administered in combination with steroids. During the course of treatment, hepatic dysfunction due to azathioprine was suspected, and the concomitant use of mercaptopurine and prednisolone was started. Afterward, the liver function improved, and the prednisolone dose was gradually reduced to 10mg/day. This is a rare case in which a thiopurine-based immunosuppressant was effective against irAE hepatitis, therefore thiopurine-based immunosuppressants may be effective against steroid-refractory hepatitis.

Portal hypertension increases the risk of hepatic decompensation after 90Yttrium radioembolization in patients with hepatocellular carcinoma: a cohort study.

Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy. We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors. In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included. We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed. In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count. Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.

Pancreatoduodenectomy after living donor liver transplant for common bile duct dysplasia

Background: Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary system characterized by fibrosing inflammatory damage of the biliary tree. Patients with PSC are at an increased risk of biliary dysplasia and cholangiocarcinoma. Early recognition and management of these conditions are challenging, especially in the setting of worsening liver function and cirrhosis.

LncRNA ZFAS1 ameliorates injury led by non-alcoholic fatty liver disease via suppressing lipid peroxidation and inflammation

BackgroundNonalcoholic fatty liver disease (NAFLD) is known to aggravate metabolic disturbance and increase the risk of complications. The purpose of the present study was to explore the mechanism underlying the clinical effects of ZFAS1 on NAFLD. MethodsExpression of the ZFAS1 RNA was quantified in patients with NAFLD through reverse transcription-quantitative polymerase chain reaction. The correlations were assessed using Pearson's correlation coefficient test. The receiver operating characteristic curve was used to evaluate the identification of ZFAS1. Commercial kits were purchased to detect the pertinent parameters to establish mice models. Luciferase report assay was used to identify and confirm the presence of ZFAS1 ceRNA. ResultsThe increase of ZFAS1 expression in patients with NAFLD was noted and the high expression level may be considered a risk factor for NAFLD. In mouse models fed with high-fat diet (HFD), the expression levels of ZFAS1 were increased; furthermore, sh-ZFAS1 reversed ZFAS1 overexpression. HFD administration resulted in liver injury, which was indicated by increased lipid deposition, aggressive oxidative stress, and imbalanced inflammatory reaction. However, sh-ZFAS1 attenuated the abovementioned adverse effects of HFD. MiR-144-5p was a ceRNA of ZFAS1; in addition, the expression of miR-144-5p was reduced in HFD-managed models and patients with NAFLD. ZFAS1 could successfully regulate the expression levels of miR-144-5p. In the present study, the negative relationship between ZFAS1 and miR-144-5p was documented. ConclusionExcessive expression of ZFAS1 and its diagnostic potential was noted in patients with NAFLD. It was evident that ZFAS1 may be responsible for exacerbating the worsening of liver function.

The importance of liver function assessment before cardiac surgery: A narrative review.

The demand for cardiac surgery procedures is increasing globally. Thanks to an improvement in survival driven by medical advances, patients with liver disease undergo cardiac surgery more often. Liver disease is associated with the development of heart failure, especially in patients with advanced cirrhosis. Cardiovascular risk factors can also contribute to the development of both cardiomyopathy and liver disease and heart failure itself can worsen liver function. Despite the risk that liver disease and cirrhosis represent for the perioperative management of patients who undergo cardiac surgery, liver function is often not included in common risk scores for preoperative evaluation. These patients have worse short and long-term survival when compared with other cardiac surgery populations. Preoperative evaluation of liver function, postoperative management and close postoperative follow-up are crucial for avoiding complications and improving results. In the present narrative review, we discuss the pathophysiological components related with postoperative complications and mortality in patients with liver disease who undergo cardiac surgery and provide recommendations for the perioperative management.

Mycophenolate-Induced Hepatotoxicity Precipitates Tacrolimus Nephrotoxicity in a Kidney Transplant Recipient: A Case Report

Mycophenolate (mycophenolate mofetil [MMF]; mycophenolate sodium [MPS]) and tacrolimus (FK-506) are commonly and concomitantly used to prevent rejection in organ transplant. Mycophenolate-induced hepatotoxicity causing the reduced FK-506 metabolism with nephrotoxicity may be less appreciated, leading to inappropriate management. We describe a new living donor kidney recipient receiving pretransplant and post-transplant immunosuppressants including oral mycophenolate (MMF 1 g daily) and tacrolimus (FK-506 4-8 mg daily) who developed progressive liver dysfunction (up to 10-fold increase) despite the reduced FK-506 dosage (6 mg daily). A thorough investigation including infection, inflammation, and autoimmune hepatitis were unremarkable. With a withdrawal of MMF, his liver function improved, but persistently higher trough serum FK-506 level (12-15 ng/mL) and increased serum creatinine were notable. Moreover, the reintroduction of MPS with the reduced FK-506 dosage (4 mg daily) worsened liver function along with FK-506 nephrotoxicity (serum creatinine from 1.4-2.4 mg/dL). The replacement of MPS with mammalian target of rapamycin inhibitor not only resolved liver injury but also normalized serum FK-506 level and kidney function. Mycophenolate should be kept in mind as a cause of drug-induced hepatotoxicity that can reduce tacrolimus metabolism, leading to FK-506 nephrotoxicity and acute kidney injury in organ transplant.

Frequency of Worsening Clinical Test Values Related to Supplement Use: Estimation by Using Nationwide Online Survey

This study examined the frequency of worsening clinical test values related to supplement use using a nationwide online survey, with a focus on liver function markers, and clarified the differences between outcome indices of diarrhea or skin manifestations. A nationwide online survey was conducted with 73,010 supplement users from the previous year. Of these, 221 individuals with worsening clinical test values responded to the full-scale survey. To compare surveys with different outcome indices, we used previously reported data from similar surveys.Only 0.5% of individuals who self-reported worsening of clinical test values caused by supplement use recognized an almost certain causal relationship. Among the test items, blood lipids were the most frequently reported. The frequency of worsening liver function markers was 0.2% in supplement users. Among those who experienced worsening clinical test values, 56.1% received no treatment and 82.4% did not report the incidence of worsening clinical test values anywhere. The ingredient-based classification of products revealed more "Peptides or animal by-products" and "Combination products/not classifiable products" than those associated with other categories. Compared to the results of the survey about the experience of diarrhea or skin manifestations, those who experienced worsening clinical test values were predominantly men, frequent and long-term users, and individuals whose products could not be identified.Few supplement users experience worsening of liver function markers, which does not seem serious. However, it is difficult for supplement users to recognize abnormal changes by themselves. Thus, it is important to record product information, usage, and changes in physical condition.

S3138 Primary Hepatic Angiosarcoma: A Rare Cause of Decompensated Pseudo-Cirrhosis and Acute Liver Failure

Introduction: Primary hepatic angiosarcoma (PHA) is a rare aggressive endothelial cell tumor which is seen in patients in their 60s and 70s with 3:1 male predominance. Industrial exposure to vinyl chloride, radium, chronic arsenic ingestion, anabolic steroid use, and iatrogenic exposure to thorotrast radiocontrast are some of the known etiologies for the development of PHA. Whereas, in most cases, attributable risk factors are rarely identified. Case Description/Methods: A 68-year-old male patient with NIDDM presented with chest pain and abdominal distension. Examination revealed marked ascites, abdominal tenderness, and bilateral leg edema. Labs were significant for thrombocytopenia and cholestatic pattern of liver enzymes with AST 94, ALT 47, ALP 413, T bilirubin 5.7. Paracentesis was negative for SBP or malignant cytology and was indicative of portal hypertensive ascites. Tumor marker workup was positive for CA 19-9 106.1, whereas negative for CEA 1.82, and AFP 2.7. CT A/P showed multifocal large heterogeneous enhancing lesions in the liver which were biopsied showing diffuse proliferation of abnormal vascular endothelial cells staining positive for CD34 and a diagnosis of PHA was made. With multifocal lesions, the patient was started on paclitaxel chemotherapy, which was eventually stopped with worsening liver function. The hospital course was complicated by hepatic encephalopathy and coagulopathy. The patient and the family later chose to transition to palliative therapy for comfort (Figure 1). Discussion: PHA is a rare and aggressive tumor with poor outcomes and an average survival rate of less than a year. Early diagnosis is challenging as it presents with nonspecific abdominal symptoms. With progression, PHA can present as decompensated pseudocirrhosis due to compression of liver parenchyma leading to portal hypertension. Contrast-enhanced US and CT can help in diagnosis by showing lesions characteristic of central non-enhancement and peripheral irregular enhancement in the arterial and portal phase, and complete wash-out in the late phase. A definitive diagnosis of PHA is established via histopathological analysis with immunohistochemistry staining but can make diagnosis more challenging due to the potential of associated bleeding. Surgical excision with negative surgical margins is the standard treatment for PHA which is localized and resectable. Multifocal and metastatic PHA is a radio-resistant tumor with a paucity of treatment options, however, TACE and/or salvage chemotherapy can be potentially attempted.Figure 1.: CT Abdomen pelvis showing multiple mass lesions occupying most of liver parenchyma.