On the question of functional diagnostics of the liver by Ѵidalа

In 1920, Vidal (1) proposed a functional liver test, substantiated by the following experimental data: if a dog takes blood from v. portae in the midst of digestion and inject it into the systemic circulation, the dog reacts to the introduction of blood by a drop in the number of leukocytes and blood pressure, a change in blood clotting time, a decrease in the refractometric index and a change in the leukocyte formula.

Case Report of Acute Liver Failure Induced By Isotretinoin Medication

Introduction: Drug induced liver injury or DILI is any injury to the liver by a medication, herb, or dietary supplement. Ranking as the first cause of acute liver failure in the USA and Europe, spectrum of clinical presentation may range from asymptomatic elevated liver function test to ALF. Approximately 20 new cases of DILI per 100,000 persons occur each year worldwide. Classified as intrinsic (with the most common cause being acetaminophen), and idiosyncratic adverse drug reaction (including mostly those related to antibiotics, NSAID drugs, and isoniazid). Isotretinoin is indicated to treat severe inflammatory acne that is refractory to antibiotics or topical agents; Although it has a high margin of safety, adverse effects include transaminasitis, like many retinoids, but unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver failure. We report a case of 31 year old lady on isotretinoin therapy for her acnea since 8 month with poor follow up, presenting with acute liver failure to our emergency department. Case Presentation: 31 year old lady , NKDFA, on isotretinoin for her acne, started 8 month ago at a dose 40mg daily, is brought by her family for decrease level of consciousness and increasing jaundice since around 5 days associated with mild abdominal disconfort. Intubated for GCS of 3, laboratory tests showed prolonged INR and elevated total bilirubin, mainly direct, with elevated transaminase levels, all work up for other etiologies turned negative, and patient was diagnosed with isotretinoin inducing acute liver failure. Discussion: Hepatotoxicity manifesting by liver test abnormalities, occur in up to 15% of patients on isotretinoin. These liver test abnormalities are usually asymptomatic and resolve spontaneously even without discontinuation of therapy in most cases. Severe liver injury due to isotretinoin is exceedingly rare: The acute liver failure was only been described with etretinate and acitretin and not with isotretinoin therapy. Risk factors for DILI include older age, female sex, African American, pharmacological risk (including daily dosage, degree of lipophilicity and extent of hepatic metabolism), preexisting liver disease and Host Genetic Factors. An important association was found between the dose of oral medication and hepatotoxicity in the United States and Sweden, in addition to a positive association between higher drug lipophilicity and DILI in condition to be coupled with high dose ingestion. Our patient meets the criteria for sex and for the pharmacological characteristic of isotretinoin (which is a highly lipophilic drug and was ingested at 40mg daily). DILI may cause cholestatic or hepatocellular liver injury or mixed on the basis of the R value, In addition, studies have showed that DILI in females is more often hepatocellular and may be associated with a more severe course, which can result in the need for liver transplant, or death and all that were compatible with our case. As the disorder is rare, there are no specific biomarkers for diagnosis of idiosyncratic DILI, and diagnosis is made by exclusion. Recent advances in the diagnosis of DILI include the recognition of the importance of the establishment of clinical networks to refine causality assessment estimated by RUCAM score and also the use of expert panels in the diagnosis of DILI [3]. The calculated RUCAM score for our case is equal to 8, indicating probable drug reaction. Concerning acute liver failure, the most widely accepted definition from the American Association for the Study of Liver Diseases (AASLD) is ‘’evidence of coagulation abnormality, usually an international normalized ratio above 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting liver disease and with an illness of less than 26 weeks’ duration’’. Based on all above, the presentation of our patient was typical for an acute liver failure induced by the drug isotretinoin. The only curative treatment of drug induced acute liver failure is liver transplantation. Conclusion: This is probably the first case reporting an acute liver failure induced by isotretinoin therapy. Strict monitoring of liver tests is highly recommended for patients receiving isotretinoin at regular intervals, with close observation and follow up, because, although rare, it may induce an acute liver failure with deleterious results. Future works must include a discovery of an early markers of DILI, for early detection and prevention in the high risk patients.

Case Report of Acute Liver Failure Induced By Isotretinoin Medication

Introduction: Drug induced liver injury or DILI is any injury to the liver by a medication, herb, or dietary supplement. Ranking as the first cause of acute liver failure in the USA and Europe, spectrum of clinical presentation may range from asymptomatic elevated liver function test to ALF. Approximately 20 new cases of DILI per 100,000 persons occur each year worldwide. Classified as intrinsic (with the most common cause being acetaminophen), and idiosyncratic adverse drug reaction (including mostly those related to antibiotics, NSAID drugs, and isoniazid). Isotretinoin is indicated to treat severe inflammatory acne that is refractory to antibiotics or topical agents; Although it has a high margin of safety, adverse effects include transaminasitis, like many retinoids, but unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver failure. We report a case of 31 year old lady on isotretinoin therapy for her acnea since 8 month with poor follow up, presenting with acute liver failure to our emergency department. Case Presentation: 31 year old lady , NKDFA, on isotretinoin for her acne, started 8 month ago at a dose 40mg daily, is brought by her family for decrease level of consciousness and increasing jaundice since around 5 days associated with mild abdominal disconfort. Intubated for GCS of 3, laboratory tests showed prolonged INR and elevated total bilirubin, mainly direct, with elevated transaminase levels, all work up for other etiologies turned negative, and patient was diagnosed with isotretinoin inducing acute liver failure. Discussion: Hepatotoxicity manifesting by liver test abnormalities, occur in up to 15% of patients on isotretinoin. These liver test abnormalities are usually asymptomatic and resolve spontaneously even without discontinuation of therapy in most cases. Severe liver injury due to isotretinoin is exceedingly rare: The acute liver failure was only been described with etretinate and acitretin and not with isotretinoin therapy. Risk factors for DILI include older age, female sex, African American, pharmacological risk (including daily dosage, degree of lipophilicity and extent of hepatic metabolism), preexisting liver disease and Host Genetic Factors. An important association was found between the dose of oral medication and hepatotoxicity in the United States and Sweden, in addition to a positive association between higher drug lipophilicity and DILI in condition to be coupled with high dose ingestion. Our patient meets the criteria for sex and for the pharmacological characteristic of isotretinoin (which is a highly lipophilic drug and was ingested at 40mg daily). DILI may cause cholestatic or hepatocellular liver injury or mixed on the basis of the R value, In addition, studies have showed that DILI in females is more often hepatocellular and may be associated with a more severe course, which can result in the need for liver transplant, or death and all that were compatible with our case. As the disorder is rare, there are no specific biomarkers for diagnosis of idiosyncratic DILI, and diagnosis is made by exclusion. Recent advances in the diagnosis of DILI include the recognition of the importance of the establishment of clinical networks to refine causality assessment estimated by RUCAM score and also the use of expert panels in the diagnosis of DILI [3]. The calculated RUCAM score for our case is equal to 8, indicating probable drug reaction. Concerning acute liver failure, the most widely accepted definition from the American Association for the Study of Liver Diseases (AASLD) is ‘’evidence of coagulation abnormality, usually an international normalized ratio above 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting liver disease and with an illness of less than 26 weeks’ duration’’. Based on all above, the presentation of our patient was typical for an acute liver failure induced by the drug isotretinoin. The only curative treatment of drug induced acute liver failure is liver transplantation. Conclusion: This is probably the first case reporting an acute liver failure induced by isotretinoin therapy. Strict monitoring of liver tests is highly recommended for patients receiving isotretinoin at regular intervals, with close observation and follow up, because, although rare, it may induce an acute liver failure with deleterious results. Future works must include a discovery of an early markers of DILI, for early detection and prevention in the high risk patients.

Impact of Liver Test Abnormalities and Chronic Liver Disease on the Clinical Outcomes of Patients Hospitalized with COVID-19

<b><i>Background and Aims:</i></b> The impact of SARS-CoV-2 infection on the liver and the possibility of chronic liver disease (CLD) as a risk factor for COVID-19 severity is not fully understood. Our goal was to describe clinical outcomes of COVID-19 inpatients regarding the presence of abnormal liver tests and CLD. <b><i>Methods:</i></b> A retrospective analysis of patients with SARS-CoV-2 infection, hospitalized in a tertiary center in Portugal, was performed. Studied outcomes were disease and hospitalization length, COVID-19 severity, admission to intensive care unit (ICU) and mortality, analyzed by the presence of abnormal liver tests and CLD. <b><i>Results:</i></b> We included 317 inpatients with a mean age of 70.4 years, 50.5% males. COVID-19 severity was moderate to severe in 57.4% and critical in 12.9%. The mean disease length was 37.8 days, the median hospitalization duration 10.0 days and overall mortality 22.8%. At admission, 50.3% showed abnormal liver tests, and 41.5% showed elevated aminotransferase levels, from which 75.4% were mild. Elevated aminotransferase levels at admission were associated with COVID-19 severity (78.7 vs. 63.3%, <i>p</i> = 0.01), ICU admission (13.1 vs. 5.92%, <i>p</i> = 0.034) and increased mortality (25.8 vs. 13.3%, <i>p</i> = 0.007). However, in a subgroup analysis, only aspartate transaminase (AST) was associated with these worse outcomes. Alkaline phosphatase was elevated in 11.4% of the patients and was associated with critical COVID-19 (21.1 vs. 9.92%, <i>p</i> = 0.044) and mortality (20.4 vs. 9.52%, <i>p</i> = 0.025), while 24.6% of the patients showed elevated γ-glutamyl transferase, which was associated with ICU admission (42.3 vs. 22.8%, <i>p</i> = 0.028). Fourteen patients had baseline CLD (4.42%), 3 with liver cirrhosis. Alcohol (<i>n</i> = 6) and nonalcoholic fatty liver disease (<i>n</i> = 6) were the most frequent etiologies. CLD patients had critical COVID-19 in 21.4% (<i>p</i> = 0.237), mean disease length of 36.6 days (<i>p</i> = 0.291), median hospitalization duration of 11.5 days (<i>p</i> = 0.447) and a mortality rate of 28.6% (<i>p</i> = 0.595), which increased to 66.7% among cirrhotic patients (<i>p</i> = 0.176). <b><i>Conclusions:</i></b> Liver test abnormalities in COVID-19 patients were frequent but most commonly mild. AST, but not alanine transaminase, was associated with worse clinical outcomes, such as COVID-19 severity and mortality, probably indicating these outcomes were independent of liver injury. A low prevalence of CLD was seen, and a clear impact on COVID-19 outcomes was not seen.

SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.

Evaluation of the frequency of gastrointestinal symptoms and liver test disorder in patients during the Covid-19 outbreak in the Military Unit: A single-center pilot study.

BackgroundAlthough Covid-19 is often a disease presenting with respiratory symptoms, gastrointestinal (GI) symptoms can also be seen. Also, there may be disruptions in liver enzyme during the disease. In our study, we aimed to investigate the extent of the military co-epidemic during the Covid-19 epidemic process and the frequency of GI symptoms and liver test disorders.MethodsThe demographic, radiological, laboratory, and clinical analysis of the soldiers diagnosed Covid-19 with real-time polymerase chain reaction, was carried out retrospectively in March, April, and May of 2020.ResultsCovid-19 was detected in 17 (0.7%) of the 2152 soldiers coming from different cities to perform their military service, in the following days after being recruited, in 9 (0.4%) of the soldiers. While 1 (0.3%) of 320 senior military and 2 (3.6%) soldiers from 56 other soldiers who came to the unit from other units were also diagnosed with Covid-19.The mean age was 21.2 ± 1.8. In Torax CT, only 4 (13.7%) patients had pneumonia. At the time of diagnosis, 6.8% of the patients had GI symptoms and 13.7% of them had liver enzyme disruption. None of the patients experienced respiratory failure, intensive care, and death, and all patients recovered.ConclusionIn the literature, our study is the first study to investigate the Covid-19 outbreak in the military unit in the world and the frequency of GI symptoms and liver enzyme disruptions in these patients. In our study, Covid-19 was milder in the young population and we found that GI symptom and liver test disorder were observed less frequently. Covid-19 outbreak can be taken under control by fast and accurate triage and suitable isolation for those with suspected disease, in environments where many people such as military units will live close together. Especially in patients with GI symptoms, Covid-19 should always be kept in mind and early isolation of patients can prevent the spread of the epidemic in such crowded environments.