Monitoring Of Liver Function Research Articles

Toxic Effects of Treatment with Cyclophosphamide on Serum Biochemical Markers of Hepatic Function in Albino Rats

Despite being an effective modality of treatment against cancer, chemotherapy is a major factor responsible for the morbidity and mortality caused by cancer. Cyclophosphamide, a widely used chemotherapeutic drug belonging to the Nitrogen Mustard family of alkylating agents, has been documented for many side- effects on the healthy tissues and metabolism of individuals undergoing treatment. In the present study, an effort has been made to investigate the effects of cyclophosphamide administration on hepatic metabolism of albino rats. Male albino rats were divided into two groups (n= 6 in each). Group 1 (Vehicle control) rats were treated with distilled water and group II rats were intraperitoneally administered with single dose of cyclophosphamide at the dose of 200 mg/kg b wt on day 1 of the experiment. Blood was collected from rats of each group on day 7 via cardiac puncture. Serum was separated and analysed for level of liver function markers and lipid profile parameters. Intraperitoneal administration of cyclophosphamide resulted in a significant increase in serum level of bilirubin and liver enzymes-- Serum Glutamic Pyruvic Transaminase (SGPT), Serum Glutamic Oxaloacetic Transaminase (SGOT) and Alkaline Phosphatase (ALP) (P<0.001), while decreased the level of total protein (P<0.01), albumin (P<0.05) and globulin, when compared to vehicle control group rats. A significant increment in serum level of Total Cholesterol (TC), Low Density Lipoprotein (LDL-c), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL- c) along with a significant decrease in High Density Lipoprotein (HDL-c) was observed following cyclophosphamide administration in group II rats, when compared to control group (P<0.001)Cyclophosphamide caused severe biochemical alterations resulting in hepatic toxicity, increased lipid peroxidation and redox imbalances in albino rats. Therefore, a routine monitoring of liver function might be advisable for the individuals undergoing chemotherapy as well as before recommending the chemotherapy session.

Pharmacokinetic/Pharmacodynamic Determinations of Iron-tannic Molecular Nanoparticles with its Implication in MR Imaging and Enhancement of Liver Clearance.

Assessment and enhancement of liver clearance are promising strategies for protection of liver from various liver diseases. Iron-tannic nanoparticles (FTs) were previously considered as imageable autophagic enhancers with biodegradation potential. Herein, we present a new approach for utilizing Iron-tannic nanoparticles (FTs) as a tool for imaging and increasing liver clearance. Pharmacokinetic profiling suggested that FTs were initially found in blood circulation and thereafter were distributed to the liver. By using MR imaging (T1 weighted), maximum MRI signal enhancement was found to occur after 30 minutes post-injection (i.v.) and gradually decreased afterward. Decreasing MRI signal may be due to FTs metabolism by the liver. By assessing imaging-derived pharmacokinetics, we can simply determine the rate constant of liver degradation of FTs. Potentially, we might use this parameter to monitor liver function, where its clearance is of concern. Once functional implication of FTs in liver clearance was investigated, FTs were found to induce hepatocyte autophagy along with activation of lysosomes. Consequently, the hepatocytes were capable of efficiently clearing cellular debris. From these results, it is clear that FTs should be considered as a molecular tool for quantitative MRI-derived liver function assessment, and for enhancing clearance function in liver parenchyma. Hopefully, our findings will pave the way to develop new strategies for non-invasive assessment and enhancement of liver clearance.

COVID-19 is associated with a high prevalence of liver damage: a systematic review and meta-analysis

Introduction: The Coronavirus Disease 2019 (COVID-19) outbreak is a serious threat to humans, and the impact of COVID-19 on the liver remains unexplored. At present, no meta-analysis has summarized available findings of COVID-19 patients with liver injury in depth. Thus, we aimed to scrutinize the association of the liver in COVID-19 patients and approximate the prognosis of COVID-19 patients with liver injury thoroughly. Method: We searched different databases for qualified studies between December 2019 to May 2021. Finally, meta-analysis was carried out using fixed-effect or random-effect models based on the heterogeneity. Result: Our Meta-analysis includes 32 studies with a total of 6,933 COVID-19 patients. The pooled prevalence of chronic liver disease (CLD) was 3.5%. Overall, the rates of severity and mortality in COVID-19 patients with underlying CLD were 4.6% and 19.2%, respectively. Additionally, the incidence of acute on chronic failure (ACLF) among COVID-19 patients with CLD was 25.1%. The prevalence of an increase in serum ALT, AST, TBil, and LDH levels was 39.5%, 28.6%, 26.5%, and 55.5%, respectively. Similarly, PT was prolonged in 8.3% of cases, and albumin was decreased in 66.8% of cases. The pooled prevalence of liver injury among COVID-19 patients was 28.2%. Strikingly, the patients with liver injury had significantly more severe disease (42.3%) and a higher incidence of mortality (18.5%) than the patients without liver injury. Conclusion: In conclusion, more than one in five of the COVID-19 patients is at risk of developing a liver injury. Further, patients with liver injury have significantly more severe disease and a higher incidence of mortality than patients without liver injury. Thus, careful monitoring of liver function is advisable while treating COVID-19 patients.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

Postmortem Liver Pathology Findings in Patients With COVID-19: A Systematic Review

Background: The Coronavirus Disease 2019 (COVID-19) pandemic promptly became a significant public health challenge with extra-pulmonary manifestations, including liver damage. Postmortem examination is crucial for gaining a better understanding of these manifestations and improving patient management. This study summarized the current knowledge of the postmortem liver pathology of patients with COVID-19. Methods: This review was conducted on studies evaluating the postmortem macroscopic and microscopic findings of the liver in patients with COVID-19. Accordingly, we searched 4 electronic databases (PubMed, Scopus, Google Scholar, & Web of Science) until June 2021. From the 317 screened articles, 16 articles examining a total of 332 patients who had died due to COVID-19 were selected. Results: The significant findings of the liver were moderate macro and microvesicular steatosis with mild sinusoidal dilation, active lobular and portal vein thrombosis, mildly-increased lymphocyte filtration in sinusoidal space, and multifocal hepatic necrosis. Additionally, the most common comorbidities were hypertension and other metabolic diseases. In conclusion, liver damage due to COVID-19 infection has various manifestations in patients who have expired due to COVID-19. Conclusion: Therefore, monitoring liver function during the course and treatment of this disease is necessary for better patient management and to decrease the COVID-19-induced mortality rate COVID.

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a reversible cholestatic condition specific to pregnancy, characterized by pruritus, hepatic cytolysis and elevated serum bile acids. It usually starts at the end of the second or third trimester and is reversible rapidly after delivery. Incidence is higher in South American and Scandinavian countries (9.2-15.6% and 1.5% respectively) than in Europe (0.1-0.2%). Its aetiology is multifactorial, including genetic, endocrine and environmental factors. The maternal prognosis is usually benign, while fetal complications such as preterm birth, meconium apraxia, fetal distress and sudden intrauterine fetal death not infrequently lead to considerable perinatal morbidity and mortality. Ursodeoxycholic acid has proven to be the most effective therapeutic agent with proven safety and efficacy. Management of cholestasis of pregnancy (CP) consists of close monitoring of maternal liver function and serum bile acid levels, in addition to assessment of the fetal biophysical profile and delivery at the optimal time after fetal lung maturity. This article summarizes current information on CP based on recent literature data and presents an update on the diagnosis and management of this pathology.

78: Using pre-visit planning and electronic health record messaging to improve liver function and annual lab monitoring in the pediatric cystic fibrosis clinic

78: Using pre-visit planning and electronic health record messaging to improve liver function and annual lab monitoring in the pediatric cystic fibrosis clinic

96: Monitoring liver function tests (LFTs) for cystic fibrosis patients on elexacaftor/tezacaftor/ivacaftor

96: Monitoring liver function tests (LFTs) for cystic fibrosis patients on elexacaftor/tezacaftor/ivacaftor

COVID-19 among African Americans and Hispanics: Does gastrointestinal symptoms impact the outcome?

BACKGROUNDThe coronavirus disease 2019 (COVID-19) disproportionately affected African Americans (AA) and Hispanics (HSP). AIMTo analyze the significant effectors of outcome in African American patient population and make special emphasis on gastrointestinal (GI) symptoms, laboratory values and comorbiditiesMETHODSWe retrospectively evaluated the medical records of 386 COVID-19 positive patients admitted at Howard University Hospital between March and May 2020. We assessed the symptoms, including the GI manifestations, comorbidities, and mortality, using logistic regression analysis.RESULTSOf these 386 COVID-19 positive patients, 257 (63.7%) were AAs, 102 (25.3%) HSP, and 26 (6.45%) Whites. There were 257 (63.7%) AA, 102 (25.3%) HSP, 26 (6.45%) Whites. The mean age was 55.6 years (SD = 18.5). However, the mean age of HSP was the lowest (43.7 years vs 61.2 for Whites vs 60 for AAs). The mortality rate was highest among the AAs (20.6%) and lowest among HSP (6.9%). Patients with shortness of breath (SOB) (OR2 = 3.64, CI = 1.73-7.65) and elevated AST (OR2 = 8.01, CI = 3.79-16.9) elevated Procalcitonin (OR2 = 8.27, CI = 3.95-17.3), AST (OR2 = 8.01, CI = 3.79-16.9), ferritin (OR2 = 2.69, CI = 1.24-5.82), and Lymphopenia (OR2 = 2.77, CI = 1.41-5.45) had a high mortality rate. Cough and fever were common but unrelated to the outcome. Hypertension and diabetes mellitus were the most common comorbidities. Glucocorticoid treatment was associated with higher mortality (OR2 = 5.40, CI = 2.72-10.7). Diarrhea was prevalent (18.8%), and GI symptoms did not affect the outcome.CONCLUSIONAfrican Americans in our study had the highest mortality as they consisted of an older population and comorbidities. Age is the most important factor along with SOB in determining the mortality rate. Overall, elevated liver enzymes, ferritin, procalcitonin and C-reactive protein were associated with poor prognosis. GI symptoms did not affect the outcome. Glucocorticoids should be used judiciously, considering the poor outcomes associated with it. Attention should also be paid to monitor liver function during COVID-19, especially in AA and HSP patients with higher disease severity

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.

Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

P-98 BIOCHEMICAL MAKERS AMONG CHRONIC LIVER DISEASE PATIENTS ACCORDING COVID-19 INFECTION: A FOLLOW-UP STUDY

IntroductionCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human health and the economy. Chronic Liver disease (CLD) patients could be at high risk for COVID-19. At this moment, there is little data about biochemical variation according to liver disease along to COVID-19 infection.ObjectivesThis study aims to report the levels of biochemical markers in CLD patients with or without COVID-19 to give more information that could help clinical monitoring.MethodsA total of 66 CLD patients were included in this study during year of 2020. Study was approved by Brazilian Ethics Committee. Blood and respiratory samples were collected after signed informed consent. At baseline and during follow-up, all subjects included in this study underwent routine examination, monitoring of biochemical markers, and SARS-CoV-2 nucleic acid testing with a median follow-up interval of 15 days.ResultsMost of individuals were male 56% (37/66) and mean age of population was 49±17 years. Six out 66 CLD patients were SARS CoV-2 RNA positive at baseline. At the end of follow-up, all these 6 patients achieved SARS-CoV-2 clearance. At least once during follow-up, the CLD group versus CLD/COVID-19 group, 50% (30/60) vs. 33% (2/6) had abnormal alanine aminotransferase; 47% (28/60) vs. 17% (1/6) had abnormal aspartate aminotransferase; 60% (36/60) vs. 67% (4/6) had abnormal γ-glutamyltransferase, 32% CLD patients (19/60) had abnormal total bilirubin levels vs. none of the CLD/COVID-19 group.ConclusionsPrevious liver disease did not seem to increase the biochemical levels, except GGT, during COVID-19 infection. However, liver function monitoring is still essential for both COVID-19 patients with and without liver disease.

P-117 LOW PREVALENCE OF HEPATITIS B AND C AMONG PEOPLE LIVING IN POVERTY IN NORTHEAST BRAZIL

Hepatitis B and C infection are responsible for more than 300 million of chronic liver disease patients all over the world. One goal of WHO 2030 agenda is the eradication of hepatitis B and C. However poverty is a great obstacle to achieve this goal. In Brazil, more than 13 million of people live in poverty (PLP) and could be vulnerable to HBV and HCV. This study aims to determine HBV and HCV prevalence and analyze the response to HBV vaccination by measuring anti -HBs antibodies in serum samples from PLP. This was a cross­ sectional study carried out in rural settlement in the municipality of Sao Joao do Piaui, Northeast Brazil in March and July 2019. Participants were recruited in their homes and after signing the informed consent, they gave blood samples. A commercial ELISA was use d for measurements of antibodies against i) hepatitis B surface antigen (anti-HBs) and ii) hepatitis B core antigen (HBc) and of the hepatitis surf ace antigen (HBsAg). Nearly half of the population was female (51.0%). The mean age was 36.2±20.4 years, and about 43.2% received a monthly income of approximately $35.00 USD. Most are self­declared black or mixed race (81.9%), were married (50.1%), 15.5% was illiterate and 25.8% had a maximum of six years of formal schooling. Overall zero positivity for HBsAg, anti-HBc and anti -HBs determined by ELISA was 0.2%, 5.1 % and 43.9%, respectively. Anti-HBs reactivity was not associated with monthly income and schooling. Low rates of vaccination against hepatitis B were found among PLP in Northeast Brazil, highlighting the need for preventive actions towards this population segment, vulnerable and a potential disseminator of this infection. Strategies to increase HBV vaccination will be essential to eradicate hepatitis Band achieve the goals of WHO 2030 agenda. Report the levels of biochemical markers in CLD patients with or without COVID-19 to give more information that could help clinical monitoring. Study was approved by Brazilian Ethics Committee. Blood samples were collected after signed informed consent. Most of individuals were male 56% (37/66) and mean age of population was 49±17 years. Six out 66 CLD patients were SARS CoV-2 RNA positive at baseline. At the end of follow-up, all of these 6 patients achieved SARS-CoV-2 clearance. At least once during follow-up, the CLD group versus CLD/COVID-19 group, 48% (29/60) vs. 17% (1/6) (P = 0.2) had abnormal alanine aminotransferase; 47% (28/60) vs. 17% (1/6) had abnormal aspartate aminotransferase (P = 0.21); 60% (36/60) vs. 67% (4/6) had abnormal γ-glutamyl transferase (P = 1.00), 32% CLD patients (19/60) had abnormal total bilirubin levels vs. none of the CLD/COVID-19 group (P = 0.17). Previous liver disease did not seem to increase the biochemical levels, except GGT, during COVID-19 infection. However, liver function monitoring is still essential for both COVID-19 patients with and without liver disease.

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma

SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p= 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p= 0.07; Child-Pugh 6, p <0.05; prior TACE, p= 0.08). SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that mayaffect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.

Cystic Fibrosis Transmembrane Conductance Regulator Modulators During Pregnancy: A Case Series

Cystic fibrosis (CF) is the most common genetic disease in the United States (US) and, with the development of newer therapeutics, there is increased fertility among women with CF. We present a series of pregnant patients taking novel CF transmembrane conductance regulator (CFTR) modulators and summarize pertinent clinical considerations. All women conceived within four months after starting elexacaftor-ivacaftor-tezacaftor. Pulmonary function was stable before and during pregnancy. One patient developed transaminitis necessitating discontinuation of the medication mid-trimester. All patients delivered healthy neonates between 36-38 weeks of gestation with uncomplicated postpartum courses. No birth defects were encountered. Given that newly introduced CFTR modulators may increase fertility among CF patients, contraception counseling, pulmonary function monitoring, liver function monitoring, and multi-disciplinary care are important pillars of management.

Periocular Necrobiotic Xanthogranuloma Response to Cladribine.

A 42-year-old woman presented to the Ophthalmology department with bilateral large nodular lesions around her eyes for the past 2 years (panel A). On examination, yellow to skin colored, ill as well as well-defined multiple papules and nodules were noted around the periorbital area, forehead, and neck. Many papules had coalesced to form large plaques. Blood investigations including electrophoresis were performed to rule out paraproteinemia. A biopsy from the periocular lesion revealed necrobiotic granulomatous inflammation, atypical giant cells, cholesterol clefts, plasma cells, and minimal fibrosis. A diagnosis of xanthogranuloma necrobiotica was made. Intralesional steroids were injected, and the patient was started on oral steroids. However, there was no response. Eventually, 4 cycles of intravenous cladribine were administered with routine monitoring of liver function, kidney function, and other blood parameters. A marked reduction in the size of the lesions were noted. (Panel B) There was no obvious systemic adverse reaction of the drug and the lesions did not flare up once the chemotherapy was halted. Necrobiotic xanthogranuloma is a rare, chronic and gradually progressive disease characterized by yellowish plaque lesions typically involving the periorbital area and unlike other orbital xanthogranulomas, having a high propensity to ulcerative and fibrose. The clinical condition principally involves the skin and subcutaneous tissue and is known to be associated with characteristic dermatopathologic findings, monoclonal gammopathy, and less commonly malignant tumors. Medical management including chemotherapy with alkylating agents and antimetabolites as well as administration of intralesional, topical and systemic steroids has yielded varied results. Although multiple other modes of treatment have also been advocated in the management of xanthogranuloma necrobiotica ranging from, radiation therapy, plasmapheresis, surgical excision, or a combination of them, there still remains a dispute regarding the definite management. In the recent times, cladribine has shown encouraging results in the management of xanthoma disseminatum, with that knowledge in background the authors used the drug in the management of xanthogranuloma necrobiotica.FIG.: A, Clinical picture of the patient at presentation showing bilateral huge periocular nodular lesions. B, Clinical picture of the patient after 4 cycles of Cladribine showing reduction in size of the lesions.

A cross-sectional survey of hospitalization and blood tests implementation status in patients who received tolvaptan under 75 years of age using a Japanese claims database

ABSTRACT Background Hypernatremia and liver injury are typical adverse effects of tolvaptan. Therefore, hospitalization and frequent monitoring of serum sodium concentration and liver function are necessary for tolvaptan initiation. We performed a cross-sectional survey to evaluate these situations. Research design and methods We employed the Japanese claims database, which contains data of patients aged < 75 years. Patients who were newly prescribed tolvaptan for fluid accumulation induced by chronic heart failure (FA-CHF) or liver cirrhosis (FA-LC) from January 2011 to June 2017 were included. We evaluated the hospitalization status and implementation of serum sodium and liver function tests in the evaluation period, based on the Japanese package insert. Results Of 1,173 patients, 347 and 117 were enrolled in FA-CHF and FA-LC groups, respectively. Among them, 10.7% (FA-CHF group) and 5.13% (FA-LC group) were prescribed tolvaptan without hospitalization. In the FA-CHF group, 11.0% and 17.6% did not undergo serum sodium and liver function tests even once in the evaluation period, respectively, compared with 12.0% and 12.8% in the FA-LC group. Conclusions Our results highlight the deviation from Japanese package insert recommendations. This approach can be applied to other drugs and provides important perspectives on pharmacovigilance research.

European guideline on indications, performance and clinical impact of 13 C-breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC.

Introduction 13C‐breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers.MethodsThis consensus‐based clinical practice guideline defines the clinical indications, performance, and interpretation of 13C‐breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed.ResultsThe guideline gives an overview over general methodology of 13C‐breath testing and provides recommendations for the use of 13C‐breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of 13C‐breath testing are summarized briefly. The recommendations specifically detail when and how individual 13C‐breath tests should be performed including examples for well‐established test protocols, patient preparation, and reporting of test results.ConclusionThis clinical practice guideline should improve pan‐European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, this guideline identifies areas of future clinical research involving the use of 13C‐breath tests.

Relative risk of hepatotoxicity associated with cyclin-dependent kinase inhibitors (CDK4/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials.

e13037 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib, and ribociclib have changed the landscape of management of estrogen receptor-positive and HER2-negative breast cancer in recent years. We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hepatic dysfunction associated with the use of CDK4/6i. Methods: We conducted a systematic search using PRISMA guidelines in PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer Symposium meeting abstracts from inception through Jan 30, 2021. Phase 3 RCTs using CDK4/6i in the intervention arm and reporting the number of events for elevation of liver enzymes were included in the analysis. The Cochran-Mantel-Haenszel method and random effects model were used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested by Cochran’s Q test and I2 value. Results: Nine phase 3 RCTs — MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH 2, MONARCH 3, MONARCH plus, monarchE, PALOMA-2, and PALOMA-3 — randomizing 5,809 patients in the CDK4/6i arms and 4,638 patients in the control arms were included in the analysis. The CDK4/6i arms used CDK4/6i such as palbociclib, abemaciclib, or ribociclib in combination with one of the standard-of-care endocrine therapies such as letrozole, anastrozole, tamoxifen, or fulvestrant. The control arms received placebo along with respective endocrine therapies. The incidence of any grade alanine aminotransferase (ALT) elevation was 13.1% in the CDK4/6i arm and 5.4% in the control arm, pooled RR: 2.18, 95% CI: 1.74-2.72, P &lt; 0.00001, I2 = 45%. The incidence of any grade aspartate aminotransferase (AST) elevation was 12.5% in the CDK4/6i arm and 5.3% in the control arm, pooled RR: 2.00, 95% CI: 1.57-2.54, P &lt; 0.00001, I2 = 57%. The incidence of grade 3/4 ALT elevation was 4.1% in the CDK4/6i arm and 0.8% in the control arm, pooled RR: 4.43, 95% CI: 3.08-6.37, P &lt; 0.00001, I2 = 0%. The incidence of grade 3/4 AST elevation was 2.9% in the CDK4/6i arm and 0.9% in the control arm, pooled RR: 2.70, 95% CI: 1.75-4.19, P &lt; 0.00001, I2 = 29%. No fatal case of hepatotoxicity has been reported. Conclusions: Cyclin-dependent kinase 4/6 inhibitors are associated with significant risk of any grade and grade 3/4 hepatic enzymes elevation. Regular monitoring of liver function is a key to early detection and initiation of appropriate management.

Landscape of Hepatobiliary Adverse Drug Reactions Related to Preparations Containing Psoraleae Fructus and Its Application in Pharmacovigilance

To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance. A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed. There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion. Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.