Severe Liver Failure Research Articles

Gastrointestinal Manifestations of CML: A Systematic Review

IntroductionChronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by overproduction of mature granulocytes. Up to half of the patients are asymptomatic and diagnosed during routine blood investigations; others present with fatigue and non-specific symptoms. Many patients develop gastrointestinal manifestations such as abdominal pain, bloody diarrhea, and pancreatitis during the disease course. Some presentations are related to leukemia itself, while others may be related to CML treatment.MethodsWe searched the English literature (PubMed, SCOPUS, and Google Scholar) for studies, reviews, case series, and case reports of patients with CML who developed any gastrointestinal manifestations involving the gastrointestinal tract from the esophagus down to the rectum Inclusion criteria comprised of patients above 18 years of age, with CML and gastrointestinal features. Pregnant women and bone marrow transplant recipients were excluded. Search terms included chronic myeloid leukemia, chronic myelogenous leukemia, with esophagitis, pancreatitis, duodenitis, gastritis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, hepatocellular carcinoma, cholangiocarcinoma, colon cancer, malignancy, hepatitis, primary biliary cholangitis, primary biliary cirrhosis, primary sclerosing cholangitis, and perforation.ResultsA total of 129 patients were included. Patient characteristics are shown in table 1. Among the gastrointestinal manifestations, the most common treatment-related complications were drug-related hepatitis followed by reactivation of viral hepatitis B, pancreatitis, and typhlitis. Hepatitis in CML was reported with different TKIs but more commonly with imatinib. Reactivation of viral hepatitis B was common, while hepatitis C reactivation was rarely reported. Pancreatitis was associated mostly with nilotinib. Colitis is seen mainly with dasatinib. Inflammatory bowel diseases, liver diseases such as primary biliary cholangitis (PBC), were variable; some occurred after CML diagnosis while others preceded the diagnosis. Malignancies like pancreatic adenocarcinoma and hepatocellular carcinoma occurred after CML.DiscussionGastrointestinal features in patients with chronic myeloid leukemia can be the first presenting featuring of leukemia itself, arising during the course of CML or as a complication of the treatment. Interestingly, most of these presentations have been reported in patients with CML. These include inflammatory conditions such as pancreatitis and esophagitis, reactivation of viral hepatitis to the neoplastic process, and malignancy. In patients with CML, malignant tumors in the gastrointestinal tract can be caused by leukemic infiltration. Moreover, like other myeloproliferative neoplasms, CML confers a risk of developing a second non-hematological malignancy, including colonic neoplasms.Gastrointestinal complications can pose drastic impacts throughout the disease course; they may result in a change in the treatment, affect the prognosis, and may also be fatal, as in severe enterocolitis or fulminant liver failure. The treatment goal in patients with CML has changed significantly over the last decades. The current treatment goal is to achieve normal survival and good quality of life without the need for lifelong treatment. The improvement in CML treatment and prognosis is largely attributed to the introduction of tyrosine kinase inhibitors. However, most gastrointestinal features associated with treatment are related to tyrosine kinase. The exact pathogenesis of TKI injury is unclear but likely attributed to immune-related mechanisms. Imatinib is the first-line therapy for CML and is the most widely used TKI; however, not all the gastrointestinal features are associated with imatinib as expected. Various gastrointestinal features are prominent with other TKIs as well. Appropriately identifying which TKI is the likely trigger will help in avoiding highly suspected gastrointestinal complications or guide in switching to a safer TKI, thereby achieving treatment goals.ConclusionPatients with chronic myeloid leukemia can have a different gastrointestinal presentation which can alter their disease course. Such complications must be managed appropriately in order to improve outcome and quality of life in this group of patients and maintain treatment goals. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Systematic Review of Antifungal-Induced Acute Liver Failure.

Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but long-standing clinical challenge. We aimed to approximate the risk of clinical acute liver injury among users of oral antifungals in the general population. This review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Six articles were included, comprising case reports and cohort studies, after eliminating duplicate publications. No randomized control studies were found. In all studies, the duration of antifungal use was associated with significantly increased liver enzyme levels.Although it is not very common for patients on antifungals to develop acute liver failure, the prognosis is often good with swift discontinuation of the drug and proper treatment. Liver function evaluation before treatment and periodic monitoring every three to six weeks after commencement of treatment is suggested.

Combination of Trans-Resveratrol and ε-Viniferin Induces a Hepatoprotective Effect in Rats with Severe Acute Liver Failure via Reduction of Oxidative Stress and MMP-9 Expression.

Stilbenes are a major grapevine class of phenolic compounds, known for their biological activities, including anti-inflammatory and antioxidant, but never studied in combination. We aimed to evaluate the effect of trans-resveratrol + ε-viniferin as an antioxidant mixture and its role in inflammatory development an in vivo model of severe acute liver failure induced with TAA. Trans-resveratrol + trans-ε-viniferin (5 mg/kg each) was administered to Wistar rats. Resveratrol + ε-viniferin significantly decreased TBARS and SOD activity and restored CAT and GST activities in the treated group. This stilbene combination reduced the expression of TNFα, iNOS, and COX-2, and inhibited MMP-9. The combination of resveratrol + ε-viniferin had a hepatoprotective effect, reducing DNA damage, exhibiting a protective role on the antioxidant pathway by altering SOD, CAT, and GST activities; by downregulating TNFα, COX-2, and iNOS; and upregulating IL-10. Our results suggested that adding viniferin to resveratrol may be more effective in hepatoprotection than resveratrol alone, opening a new perspective on using this stilbene combination in functional diets.

S3652 SOS: A Medication Crisis

Introduction: Hepatic sinusoidal obstructive syndrome (SOS) is characterized by the absence of cirrhosis on liver biopsy, portal hypertension, and histological signs of portal sinusoidal vascular disease. It is a rare condition that often develops following hematopoietic stem cell transplantation (HSCT). We describe a case of SOS as a sequela of herbal supplement use. Case Description/Methods: A 65-year-old white woman was referred to the ED for progressive shortness of breath in the setting of new onset ascites. She had past medical history of Type 2 diabetes, hypothyroidism, and osteoarthritis. She denied the use of medication but reported taking multiple herbal supplements. She underwent paracentesis with SAAG of 1.6 and TP 2.6, which may be consistent with SOS. The liver biopsy showed porto-sinusoidal vascular disease. Small portal tracts were sclerotic with absence of normal veins. Some portal tracts contained inappropriate vascular spaces, with areas of diffuse sinusoidal dilatation. These findings were consistent with SOS and the patient was discharged with recommendation to discontinue all herbal supplements. She returned with severe liver failure and was referred to tertiary transplant center. Due to morbid obesity, she was not a candidate for liver transplant and transferred to hospice. Discussion: SOS is a rare and potentially fatal form of hepatic injury that occurs predominantly after HSCT. SOS is also observed in relation to herbal supplements containing pyrrolidine alkaloids (PAs), antineoplastic drugs, alcohol, contraceptives, and liver radiation. Mechanism of injury is believed to be toxin-induced damage to endothelial cells in the liver followed by cell necrosis and extrusion into sinusoids, leading to obstruction and congestion. Liver biopsy is the gold standard for diagnosis. Management focuses on prevention of further injury, support for complications, and liver transplantation in severe cases. The true incidence of herbal supplement induced SOS is unknown and likely underestimated. To the best of our knowledge, this is one of the very few cases describing herbal supplement use causing SOS leading to acute liver failure requiring transplantation.

S2587 COVID-19 Virus Causing Fulminant Liver Failure

Introduction: SARS-CoV-2 has now infected 179 million people worldwide. The virus is known to effect multiple organ systems, most commonly the lungs, but it is also well known that the virus affects the liver. Elevations in AST and ALT have frequently been observed in COVID-19 infection, however these elevations are usually mild to moderate. We present an extremely rare case of COVID-19 causing severe acute liver failure. Case Description/Methods: A 76 year-old male with a past medical history of hypertension and atrial fibrillation presented to the ED with fevers, altered mental status, shortness of breath, fatigue, and nausea. A SARS-CoV-2 nasal swab performed in the ED was positive. The patient had asterixis on physical examination. The patient was found to have severe transaminitis (AST 812, ALT 810, INR 2.51, T-bili 2.4) on admission. The patient had no prior history of liver disease. The patient was admitted to the ICU for acute liver failure in the setting of COVID-19 pneumonia. The patient was intubated for worsening acute hypoxic respiratory failure. The patient expired on hospital day 17. Discussion: Based on the patient’s encephalopathy on presentation, asterixis on physical exam, and severely elevated LFTs, the diagnosis of acute liver failure can be made. The patient was not hypotensive on admission and had SpO2 > 88%, so shock liver was a less likely etiology of the liver failure. Furthermore, LFTs are generally ∼35-50x the upper limit of normal in shock liver. Other causes of liver failure, such as viral hepatitis, drug induced liver injury, and acetaminophen toxicity were ruled out. The pathogenesis of hepatocellular damage seen in COVID-19 infection is still unknown. One proposed mechanism of acute liver failure as a result of COVID-19 infection is through the ACE2 receptor. It is known that SARS-CoV-2 uses the ACE2 receptor to enter and subsequently infect cells of the respiratory tract. However, ACE2 receptors are also expressed on hepatocytes and cholangiocytes. Therefore, our proposed mechanism for how our patient developed such a severe case of acute liver failure was via entry of the SARS-CoV-2 virus into hepatocytes through ACE2 receptors. This is an extremely rare case of SARS-CoV-2 causing acute liver failure. This case emphasizes the importance of monitoring liver function tests closely in COVID-19 patients. More research needs to be performed on the outcomes and possible prognostic indicators for these patients.Table 1.: Progression of Liver Disease During Hospital Course.

S2694 Severe Acute Liver Failure in a Patient With SARS-CoV-2 Infection

Introduction: Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, are regularly found to have elevated LFTs. Up to 46% had elevated AST and 35% had elevated ALT. Occasional elevations in GGT, ALP, and total bilirubin are also seen. These elevations were usually below 5 times the upper limit of normal (ULN). Less than 10% of patients had severe liver injury (ALT > 5 times ULN). Hepatic injury in COVID-19 can be attributed to numerous causes including direct injury, drug toxicity and inflammatory storm. Direct injury is thought to occur when SARS-CoV-2 binds directly to ACE-2 which are abundantly expressed in biliary and liver epithelial cells. We present the case of an 88-year-old COVID-19 patient with severe liver failure managed conservatively. Case Description/Methods: 88-year-old male with history of CHF, atrial fibrillation on Apixaban, DM-2, HTN and recent diagnosis of COVID-19 presented with shortness of breath. Vitally, he was normotensive but hypoxic. Initial labs are shown in Table 1. He denied an established history of liver disease, alcohol use or hepatotoxic drug use. Chest CTA had findings concerning for COVID-19 pneumonia and acute pulmonary embolism. He was not started on Remdesivir due to elevated LFTs. His acute hepatitis panel and acetaminophen level were negative. The patient’s LFTs continued to worsen over his hospital course (Image 1). Transfer to a tertiary liver center was not considered due to his tenuous condition, age, and comorbidities. On day five the patient’s AST and ALT started trending down. However, total bilirubin continued to rise, and ALP stayed relatively stable. His respiratory status continued to worsen, and he was eventually transitioned to comfort care. Discussion: In the absence of an established history of liver disease, alcohol abuse, or hepatotoxic drug use, we believe that our patient’s acute liver failure might have been a direct complication of COVID-19 infection. Treatment with 1-2 drugs from the following categories: hepatoprotective, anti-inflammatory, and jaundice-reducing agents including polyene phosphatidyl choline, glycyrrhizic acid, bicyclol, and vitamin E has been proposed to reduce the burden of liver injury. With the increasing number of cases of liver injury with COVID-19, it is pivotal to identify its pathogenesis, acute interventions, and potential long-term complication to treat this life-threatening condition promptly and effectively.Table 1.: demonstrating our patient’s initial labs.Figure 1.: Image 1 demonstrating lab trend of our patient over his hospital stay.

Intraoperative Indocyanine Green Retention Test of Left Hemiliver in Decision-Making for Patients With Hepatocellular Carcinoma Undergoing Right Hepatectomy

Introduction: The aim of this study was to select qualified patients with hepatocellular carcinoma (HCC) who underwent right hepatectomy (RH) via intraoperative indocyanine green retention test at 15 min (ICG-R15) of the left hemiliver, which prevents severe posthepatectomy liver failure (PHLF).Methods: Twenty HCC patients who were preoperatively planned to undergo RH were enrolled. Intraoperative ICG-R15 of left hemiliver was measured after the right Glissonean pedicle was completely blocked. Patients then underwent RH if intraoperative ICG-R15 was ≤ 10%. Otherwise, patients underwent staged RH (SRH), either associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) or portal vein ligation (PVL), followed by stage-2 RH. The comparison group consisted of patients with a ratio of standard left liver volume (SLLV) of > 40% and preoperative ICG-R15 ≤ 10% who underwent RH. The clinical outcomes of these two groups were compared.Results: Of the 20 patients, six underwent stage-1 RH, six underwent ALPPS, five underwent PVL followed by stage-2 RH, and three failed to proceed to stage-2 RH after PVL. No significant differences were found among the 17 patients who underwent stage-1 or stage-2 RH in the study group, the 19 patients in the comparison group, the 11 patients in the stage-2 RH group, and the six patients in the stage-1 RH group in incidences of PHLF, postoperative complications, hospital stay, and HCC recurrence within 1 year after RH. Compared with the stage-1 ALPPS group, the mean operative time and blood loss of the stage-1 PVL group were significantly less (p <0.001 and p = 0.022, respectively). The stage-1 PVL group had a significantly longer waiting-time (43.4 vs. 14.0 days, p = 0.016) than the stage-1 ALPPS group to proceed to stage-2 RH. After stage-2 RH, tumor recurrence within 1 year was 20% (1/5) in patients after PVL and 50% (3/6) after stage-1 ALPPS.Conclusions: Intraoperative ICG-R15 ≤ 10% of left hemiliver was valuable in intraoperative decision-making for patients who were planned to undergo RH. There is a possibility that stage-1 PVL might help to select patients with more favorable biological behavior to undergo stage-2 RH.

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data.

To investigate whether acute liver failure (ALF) leads to secondary acute myocardial injury, 100 ALF patients that were retrospectively identified in a single center based on ICD 10 codes and 8 rats from an experimental study that died early after bile duct ligation (BDL) were examined. Creatine kinase (CK), creatine kinase-MB isoenzyme (CKMB) and cardiac troponin-I (cTnI) were analyzed as markers of myocardial injury. For histological analysis, hematoxylin-eosin (HE), elastic Van Gieson (EVG), CD41 and myeloperoxidase were used to stain rat hearts. Major adverse cardiac events (MACEs) were a critical factor for mortality (p = 0.037) in human ALF. Deceased patients exhibited higher levels of CKMB than survivors (p = 0.023). CKMB was a predictor of mortality in ALF (p = 0.013). Animals that died early after BDL exhibited increased cTnI, CKMB, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels compared to controls (cTnI: p = 0.011, CKMB: p = 0.008, TNFα: p = 0.003, IL-6: p = 0.006). These animals showed perivascular lesions and wavy fibers, microthrombi and neutrophilic infiltration in the heart. MACEs are decisive for mortality in human ALF, and elevated CKMB values indicate that this might be due to structural myocardial damage. Accordingly, CKMB was found to have predictive value for mortality in ALF. The results are substantiated by data from a rat BDL model demonstrating diffuse myocardial injury.

Peripheral Arrangement of Steatosis Microvacuoles in Wilson’s Disease

A 17-year-old girl was referred for jaundice and severe liver failure (international normalized ratio, 2.4; Factor V 19%, and total bilirubin level, 85 μmol/L). Transaminase and serum GGT levels were slightly elevated. There was hemolytic anemia with a negative Coombs test and thrombocytopenia. The liver was dysmorphic with splenomegaly. There was no viral hepatitis; the IgG level reached 21 g/L without autoantibodies. Her urinary copper level was 1779 μg/24 hours (N < 0.6), ceruloplasmin level was 0.12 g/L (N > 0.2), and a high exchangeable copper to total copper ratio (23.4%; N < 8.0) and hepatic copper level (844 μg/g) supported the diagnosis of Wilson's disease.

Etiopathogenesis and Diagnostic Strategies in Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a chronic liver disease with the incidence of 10 to 17 per 100,000 people in Europe. It affects people of any age, but most often occurs in the 40–60 age group. The clinical picture is varied, from asymptomatic to severe acute hepatitis or liver failure. The disease onset is probably associated with the impaired function of T lymphocytes, the development of molecular mimicry, intestinal dysbiosis, or infiltration with low density neutrophils, which, alongside autoantibodies (i.e., ANA, ASMA), implicate the formation of neutrophil extracellular traps (NETs), as a component of the disease process, and mediate the inappropriate immune response. AIH is characterized with an increased activity of aminotransferases, elevated concentration of serum immunoglobulin G, the presence of circulating autoantibodies and liver inflammation. The result of the histological examination of the liver and the presence of autoantibodies, although not pathognomonic, still remain a distinguishing feature. The diagnosis of AIH determines lifelong treatment in most patients. The treatment is implemented to prevent the development of cirrhosis and end-stage liver failure. This work focuses mainly on the etiopathogenesis and diagnosis of AIH.

Reversal to normal anatomy after one-anastomosis/mini gastric bypass, indications and results: a systematic review and meta-analysis.

This review evaluates the indications and outcomes of one-anastomosis/mini gastric bypass (OAGB/MGB) reversal to normal anatomy. A systematic literature search and meta-analysis was performed in PubMed, Web of Science, and Scopus for articles published by October 1, 2020, including the keywords "one anastomosis gastric bypass," "OAGB," "mini gastric bypass," "MGB," "reversal," "reverse," "malnutrition," and "reversal bariatric surgery". After examining 182 papers involving 11,578 patients, 14 studies were included. A reversal was performed in 119 patients on average 23.6 months after the primary OAGB/MGB surgery. The mean body mass index (BMI) was 22.92 ± 3.47 kg/m2 and the mean albumin level was 25.17 ± 4.21 g/L at reversal. The mean length of the common channel (CC) was 383.57 ± 159.35 cm, with a mean biliopancreatic limb (BPL) length of 214.21 ± 48.45 cm. Pooled estimation of the meta-analysis of prevalence studies reported a prevalence of 1% for reversal. The major signs and symptoms of protein-energy malnutrition were the leading causes of the reversal of OAGB/MGB. Bleeding, leakage, and death due to severe liver failure were the most reported complications after reversal, with an overall incidence of 10.9%. In conclusion, OAGB/MGB reversal has a prevalence of 1% and has a complication rate of 10.9%. Protein-energy malnutrition with hypoalbuminemia was the most common etiology. The mean lengths of BPL and CC were reported as 215 cm and 380 cm, respectively, in the cases. Therefore, special attention should be paid to malnutrition in all OAGB/MGB patients during follow-up to prevent severe malnutrition and subsequent increase in reversal procedures.

Clinical experience of somatostatin for the treatment of severe posthepatectomy liver failure

Posthepatectomy liver failure (PHLF) is a major cause of morbidity and mortality after major liver resection. Postoperative excessive portal pressure could cause shear stress to the small remnant liver leading to a PHLF. This study aimed to report the clinical experience of somatostatin for portal modulation in patients with severe PHLF. This retrospective study enrolled 15 patients who received somatostatin for the treatment of PHLF between 2016 and 2019. When the patients fulfilled the 50-50 criteria (serum bilirubin > 2.9 mg/dL and prothrombin time < 50%) on or before postoperative day 5, somatostatin (3.5 μg/kg/h) was administered by continuous infusion. The discontinuation criteria were as follows: serum bilirubin < 2 mg/dL and prothrombin time ≥ 50%. Prospectively collected clinical characteristics, laboratory tests, postoperative morbidity and mortality were evaluated. The study cohort consisted of 8 patients with hepatocellular carcinoma, 6 with cholangiocarcinoma, and 1 with colon cancer liver metastasis. Seven patients (46.7%) had underlying liver cirrhosis, and 14 (93.3%) underwent major hepatectomy. The median start time of somatostatin was postoperative day 1 (range, 1-19), and the median duration of administration was 9 days (2-29 days). There was no obvious side effects or hypersensitivity related to the somatostatin. The median hospital stay was 37 days (21-249 days). The 30-day and 90-day mortality were both 6.7% (1 of 15 patients). Administration of somatostatin in the early postoperative period is considered to be effective for the treatment of PHLF. Further prospective comparative clinical trials are needed to validate this finding.

A narrative review of herb-induced liver injury

: Herb and herbal product have been used for both healthy and specific ailments. Its use as medicine or dietary supplements has increased worldwide for more than a decade due to easy access, purported harmless nature, and perceived therapeutic efficacy. Herb induced liver injury which has been recognized for many years is likely to increase. Close scrutiny on herb related safety and liver toxicities is strongly advocated. Toxic ingredients, reactive metabolites, organelle stress, bile salt export inhibition and immune response have been postulated in the pathogenesis of herb-induced liver injury (HILI). HILI is in analogy to drug induced liver injury (DILI) in following aspects (I) clinical manifestations: from asymptomatic abnormal liver tests to severe liver injury and liver failure requiring liver transplantation; (II) mechanism: idiosyncratic or intrinsic; and (III) phenotypes of injury: hepatocellular, cholestatic or mixed type. The diagnosis of HILI remains a challenge. Roussel Uclaf Causality Assessment Method (RUCAM), a structured, quantitative, effective and validated tool for HILI should be reinforced in clinical use. The pathogenetic hallmarks of genome-wide association study (GWAS), human leukocyte antigen (HLA) alleles and non-HLA genetic variants may determine the risk for HILI. Diagnostic biomarkers for HILI need to be re-investigated and reliably validated in future research for their clinical implications. Global prospective HILI registry with advances in the exploration of toxic ingredients, genetic testing and new biomarkers may better explain the pathogenesis and pathogenetic mechanism of HILI which can lead to improvement in diagnosis and treatment of DILI. Pharmacovigilance and standardized regulatory surveillance on safety and efficacy of herbs and herbal products are warranted to reduce the occurrence of HILI and its associated morbidity and mortality.

Concomitant congenital CMV infection and inherited liver diseases

Inherited liver diseases may present in infancy as cholestatic jaundice progressing to severe hepatic dysfunction. Congenital cytomegalovirus (cCMV) infection may initially involve the liver, yet in otherwise healthy hosts rarely leads to long-term hepatic disease. We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6–12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15–24 months of follow-up – the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contribution of cCMV infection to the course of the inherited primary disease, possibly leading to further compromise of the liver. We recommend screening patients with inherited liver disease for cCMV, and considering anti-viral treatment with valganciclovir to delay hepatic disease progression.

Electrolyte monitoring during regional citrate anticoagulation in continuous renal replacement therapy.

Patients with acute kidney injury who need continuous renal replacement therapy with locoregional citrate anticoagulation are at risk of citrate accumulation with disruption of the calcium balance. We aimed to evaluate the safety of detecting citrate accumulation and adjusting electrolyte disbalances during continuous venovenous hemodialysis (CVVHD) in critically ill patients with acute kidney injury using a blood sample frequency every 6 h. A prospective single center study in critically ill intensive care unit patients who suffered from acute kidney injury with the need of renal replacement therapy. We evaluated the deviations in pH, bicarbonate and calcium during CVVHD treatment with local regional citrate anticoagulation. Values indicate median and interquartile range. Severe hypocalcemia (below 1.04 mmol/L) or hypercalcemia (above 1.31 mmol/L) occurred in 10.5% and 4.8% respectively. During treatment changes of systemic ionized calcium, post-filter ionized calcium, pH and bicarbonate were corrected with protocolized adjustments. No arrhythmias or citrate accumulation were seen. The values stabilized after 42 h and after that no statistically significant changes were observed. After 42 h of citrate CVVHD, systemic ionized calcium, pH and bicarbonate levels stabilized. A blood sample frequency every 6 h is probably safe to detect citrate accumulation and to adjust the settings of electrolytes to avoid serious electrolyte disturbances in ICU patients without severe metabolic acidosis or severe liver failure.

Neonatal lupus erythematosus with diffuse iron deposition in the liver on magnetic resonance imaging

Abstract Rationale: Neonatal lupus erythematosus (NLE) is caused by transplacental transfer of maternal autoantibodies against SS-A, SS-B, and/or RNP. Symptoms include heart block, skin lesions, cytopenia, liver dysfunction, and occasionally hydrocephalus. Hepatobiliary disease in NLE should be closely monitored, since severe liver failure has been reported. Patient concerns: A 0-day-old female patient presented with nonspecific systemic erythema, liver dysfunction, and hyperferritinemia at birth, and abdominal magnetic resonance imaging indicated diffuse iron deposition in the liver but not in extrahepatic tissues. The patient had no maternal complications or findings indicating intrauterine growth retardation, oligohydramnios, or fetal ascites. Diagnoses: The patient was diagnosed with NLE based on the presence of anti-SS-A and SS-B antibodies in the maternal and cord blood. Interventions: No intervention was required. Outcomes: Her symptoms improved spontaneously. The titers of anti-SS-A and SS-B antibodies became undetectable levels on day 379, while serum anti-double stranded DNA antibody became positive without any clinical symptoms. Lessons: Since NLE with hepatobiliary disease could present with diffuse iron deposition in the liver mimicking neonatal hemochromatosis, we need to carefully evaluate and monitor this condition.

A Combined Model of Human iPSC-Derived Liver Organoids and Hepatocytes Reveals Ferroptosis in DGUOK Mutant mtDNA Depletion Syndrome.

Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients’ skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient‐specific iPSCs and corrected iPSCs‐derived high purity hepatocyte organoids (iHep‐Orgs) and hepatocyte‐like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep‐Orgs, but not control and corrected one, are more sensitive to iron overload‐induced ferroptosis, which can be rescued by N‐Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co‐activator 4 (NCOA4)‐dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep‐Orgs model in hereditary liver diseases.

093 Tracking use of Non-prescription and Herbal Supplements by Men with ED

Many patients who seek counseling from a urologist for erectile dysfunction (ED) may have already tried various therapies before coming to a physician. Studies have shown that many patients purchase illicit pharmaceuticals over the internet or obtain “natural remedies” from gas stations and other retail stores. Counterfeit imitations of common ED medications and even “100% natural products” may contain phosphodiesterase 5 inhibitors (PDE-5i) or other adulterants. Patients taking counterfeit drugs or herbal supplements for ED have experienced severe hypoglycemia, liver failure, chest pain, and priapism. If patients are taking unknown quantities of PDE-5i in combination with nitrate medications, they may experience unsafe hypotension. Due to the unknown composition of these products and potentially unpredictable interactions with medications legitimately prescribed by physicians, it is important that the prevalence of these behaviors be quantified.

Patient experiences of alcohol specialist nurse interventions in a general hospital, and onwards care pathways.

To provide insight into patient experiences of a general hospital-based alcohol specialist nurse intervention during alcohol detoxification, experiences of alcohol specialist nurse hospital-based follow-up appointments (Pathway A) as well as the experiences of patients who did not have access to this additional help post detoxification (Pathway B). A longitudinal qualitative study. A thematic analysis of semi-structured interviews (2016-2017) with 24 patient participants (N=12 in each pathway; purposive selection) 1-4weeks post-detoxification and at 3 and 6months, to identify patient experiences of these interventions. Participants gave accounts of how 'empathic' and 'straight talking' interactions with alcohol specialist nurses during detoxification helped them to 'open up' and orient towards change. After detoxification follow-up, outpatient appointments in the hospital setting were seen as supporting change in early recovery and engagement with a wider range of services. Those with no access to nurse follow-up described experiencing a 'void' in available help. Participants in both groups described barriers to engagement with community alcohol services, peer groups and access to help for mild-moderate mental health problems. Patient accounts indicate alcohol specialist nurse interventions during and after unplanned detoxification in a hospital setting can help orient patients towards change and support early recovery. Providing alcohol specialist nurse interventions in general hospitals offers one route to initiating recovery in alcohol-dependent patients. This has potential to improve the lives of those affected and to reduce related demands on hospital services, but further research is needed.

Pleural Effusion Related to Chronic Hepatitis B Virus Reactivation: A Rare Association.

In the presence of pleural effusion of unknown origin, especially if with simultaneous acute hepatitis, a viral aetiology should be suspected and pursued.The severity of liver disease and not the pleural effusion should guide antiviral treatment.