Absence Of Pre-existing Liver Disease Research Articles

Fulminant hepatic failure in pregnancy: challenges, management strategies, prognosis and outcomes

Fulminant hepatic failure is defined as a sudden, severe impairment of hepatic function leading to an encephalopathy, which occurs within eight weeks of appearance of first symptoms in the absence of pre-existing liver disease. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver function leading to significant morbidity and even mortality. Hepatic dysfunction in pregnancy may be categorized into Pre-eclampsia-associated liver diseases such as pre-eclampsia/eclampsia, the HELLP syndrome and Acute fatty liver of pregnancy (AFLP), and other causes of hepatic dysfunction namely Hyperemesis gravidarum (HG) and Intrahepatic cholestasis of pregnancy (IHCP). For this review, a search was conducted for published articles, case reports and clinical trials in MEDLINE/Pubmed from 1970 to 2020 with the keyword’s fulminant hepatic failure, acute liver failure in pregnancy, pre-eclampsia, HELLP and AFLP. We concluded that fulminant hepatic failure is one of the most dreaded complications in pregnancy in obstetrical units worldwide. Mandatory screening for etiology, early diagnosis and initiation of supportive management as soon as possible are absolutely essential to ensure better maternal and fetal outcomes. Effective communication with the obstetrician regarding timely delivery/termination of pregnancy ensures a favourable prognosis in the majority of cases. Liver transplant is a definitive life-saving option for cases of severe fulminant hepatic failure in pregnancy, and management has to be suited to each patient individually, keeping in mind the well-being of both the mother, and the child.

Liver transplantation in acute liver failure: Dilemmas and challenges.

Acute liver failure (ALF) refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease. ALF has different causes, but the clinical characteristics are strikingly similar. In clinical practice, however, inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas. ALF mortality rates used to be over 80% in the past; however, survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management. The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates. Given that liver transplantation (LT) is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression, it is very important to select accurate patients who may benefit from it. Still, emergency LT remains a lifesaving procedure for many ALF patients. However, there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner. The other problems associated with LT in ALF are the shortage of graft, development of contraindications on the waiting list, vaguely defined delisting criteria, time constraints for pre-transplant evaluation, ethical concerns, and comparatively poor post-transplant outcomes in ALF. Therefore, there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies, such as liver support systems, plasma exchange, stem cells, auxiliary LT, and so on, to enhance transplant-free survival and to fill the void created by the graft shortage

N-acetylcysteine therapy for ischaemic hepatic failure: a successful antidote

Acute liver failure (ALF) is characterised by severe liver injury with the onset of coagulopathy (INR ≥1.5) and encephalopathy in the absence of pre-existing liver disease. It is associated with a high mortality rate of 10-57%, which is largely driven by multi-organ failure, sepsis and cardiac arrhythmia. Current management focuses on identifying and treating the aetiology, providing supportive care and monitoring liver function. The use of N-acetylcysteine (NAC) therapy is well-studied in the treatment of paracetamol toxicity but is controversial in other causes of ALF. We reported the first case of ischaemic hepatic failure secondary to prolonged portal vein occlusion treated with 72 hours of NAC therapy. Although ischaemic hepatopathy is a relatively uncommon cause of ALF, it is associated with a high mortality rate. The case highlights how early use of NAC therapy may improve hepatic serology biomarkers and should warrant consideration in ALF secondary to ischaemic hepatopathy.

Acute severe autoimmune hepatitis with anti-rods and rings autoantibodies; literature first evidence.

Autoimmune hepatitis (AIH) was defined as a progressive, chronic inflammatory autoimmune liver disease (ALD). The diagnosis of AIH requires the presence of characteristic clinical and laboratory features, and the exclusion of other clinical conditions that cause chronic hepatitis and cirrhosis. AIH can have an acute onset that mimics an acute viral or toxic hepatitis or an acute severe (fulminant, ASF) presentation that satisfies criteria for acute liver. Guidelines from the European Association for the Study of Liver Diseases define ALF with absence of pre-existing liver disease, acute onset of ≤ 26 weeks, coagulopathy (international normalised ratio (INR) ≥ 1.5), and presence of hepatic encephalopathy (HE). In recent years, autoantibodies (Aab) targeting subcellular structures described as the rods and rings (R&R) pattern in HEp-2 ANA have been presented as a unique and particular case of Aab generation. These R&R structures are composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors. Aab targeting these relatively unknown structures has been observed in Hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferona/ ribavirin (IFN/RBV) therapy. We presented and characterized a case patient with R&R and SMA Aab in AIH (ASF, fatal, without liver transplantation). To the best of our knowledge, this is the first evidence described in the Literature. Our early experience showed the R&R circulating Aab in one patient with Primary Biliary Cholangitis. This work now demonstrates that R&R Aab can also be present in AIH case.

Pathophysiological mechanisms of liver injury in COVID-19.

The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19.

RARE CAUSE OF FATAL LIVER DISEASE: A CASE OF ACUTE LIVER FAILURE IN A PATIENT WITH RECENTLY DIAGNOSED METASTATIC OVARIAN CARCINOMA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Metastatic liver disease is a relatively common finding in autopsies of adults with aggressive tumors. In a majority of cases, affected patients do not have signs or symptoms of liver failure. CASE PRESENTATION: A 41-year-old previously healthy Caucasian female presented to our ED with worsening abdominal pain and shortness of breath. Her symptoms started about a week prior to the ED visit. Her PCP ordered a CT scan of chest, abdomen, and pelvis which showed an ovarian mass concerning for carcinoma with multiple hepatic and pulmonary metastases. In the ED, vital signs were normal. A distended non-tender abdomen was appreciated during the physical exam. Laboratory workup revealed leukocytosis (WBC 31.1K/UL), abnormal LFTs (AST 1525U/L, ALT 396U/L, bilirubin 3.6MG/DL, alkaline phosphatase 366U/L), renal failure (Crea 1.76MG/DL, BUN 47MG/DL), elevated lactic acid (8.1MEQ/L), INR (1.6). A repeat CT scan of the chest, abdomen, and pelvis was unchanged. The patient was started on broad-spectrum antibiotics. On day 2, the patient was noted to have the worsening of liver function (AST 4652U/L and ALT 907U/L) as well as the development of respiratory failure. She was placed on BiPAP for increased work of breathing. She was started on CRRT for refractory metabolic acidosis and the worsening of renal failure. On day 3, the patient became confused with visible jaundice, asterixis, worsening of LFTs with AST and ALT (20845U/L and 2441U/L, respectively), elevated ammonia level as well as coagulopathy. Her MELD score was 46. Unfortunately, the patient suffered a cardiac arrest (PEA) twice within an hour with ROSC. The family made the decision to proceed with the withdrawal of care. The patient expired soon after that. DISCUSSION: Acute (also known as fulminant) liver failure is characterized by severe acute liver dysfunction (INR ≥1.5 and hepatic encephalopathy) in the absence of preexisting liver disease within less than 26 weeks. The two most common causes of acute liver failure are viral and drug-induced hepatitis. Malignant infiltration is a rare cause of liver failure which has been increasingly recognized in recent years. Patients with acute liver failure in the setting of metastatic liver disease have a very poor prognosis. CONCLUSIONS: In patients with signs and symptoms of acute liver failure, it is important to rule out metastatic liver disease as a potential etiology. Unfortunately, no definitive treatment is available at this point in affected individuals since liver transplant is contraindicated in patients with metastatic liver disease not meeting oncologic criteria for cure. Reference #1: Polson J, Lee WM. AASLD position paper: The management of acute liver failure. Hepatology. 2005;41(5):1179-1197. Reference #2: Nazario HE, Lepe R, Trotter JF. Metastatic breast cancer presenting as acute liver failure. Gastroenterology & hepatology. 2011;7(1):65. DISCLOSURES: No relevant relationships by Vincent Chan, source=Web Response No relevant relationships by Artem Minalyan, source=Web Response No relevant relationships by Qian Zhang, source=Web Response

A case of cryptogenic pseudocirrhosis causing acute liver failure: when clinic and radiology work together

It is known that a wild spectrum of hepatic manifestations can be common presentations of metastatic breast cancer. Pseudocirrhosis pattern has been often described as almost always secondary to systemic chemotherapy and it is defined by morphological liver changes that mimic cirrhosis including capsular retraction, nodularity, parenchyma atrophy and caudate lobe, radiologically identifiable. Acute liver injury is an occasional complication in oncologic patients, and it outlines an organ failure when there is evidence of encephalopathy and coagulopathy (international normalized ratio >1.5) in the absence of pre-existing liver disease, with an illness of <26 weeks duration. The two most common etiologies are leukemia/lymphoma followed by breast cancer but also in this case, liver is involved almost always after chemotherapy, hormonotherapy or radiotherapy. Here we present a case of rapid evolving acute liver failure presented as cryptogenic pseudocirrhosis without any evidence of primitive breast cancer but an incidental demonstration.

6-Mercaptopurine-Induced Non-Cirrhotic Portal Hypertension With Rapid Progression to Liver Cirrhosis in the Absence of Pre-Existing Liver Disease

6-Mercaptopurine-Induced Non-Cirrhotic Portal Hypertension With Rapid Progression to Liver Cirrhosis in the Absence of Pre-Existing Liver Disease

Acute Liver Failure Meets SOPH Syndrome: A Case Report on an Intermediate Phenotype

Acute liver failure (ALF) is a life-threatening condition in the absence of preexisting liver disease in children. The main clinical presentation comprises hepatic dysfunction, elevated liver biochemical values, and coagulopathy. The etiology of ALF remains unclear in most affected children; however, the recent identification of mutations in the neuroblastoma amplified sequence (NBAS) gene in autosomal recessively inherited ALF has shed light on the cause of a subgroup of fever-triggered pediatric ALF episodes. Previously, biallelic mutations in NBAS have been reported to be associated with a syndrome comprising short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) specifically occurring in the Yakut population. No hepatic phenotype has been observed in individuals with this disorder who all carry the homozygous NBAS founder mutation c.5741G>A [p.(Arg1914His)]. We present the case of a 4-year-old girl with the cardinal features of SOPH syndrome: characteristic facial dysmorphism, postnatal growth retardation, delay of bone age, slender long bones, optic atrophy, and Pelger-Huët anomaly. During the first 2 years of her life, a series of infections with episodes of fever were accompanied by elevated liver enzyme levels, but hyperammonemia, hypoglycemia, coagulopathy, or encephalopathy suggestive of acute and severe liver disease were never observed. Whole exome sequencing in the patient revealed compound heterozygosity of the 2 NBAS variants, p.(Arg1914His) and p.(Glu943*). This case highlights the variability of clinical presentation associated with NBAS deficiency. Absence of severe liver problems in this case and SOPH-affected Yakut subjects suggests that individuals carrying the NBAS missense mutation p.(Arg1914His) are less susceptible to developing ALF.

Acute Liver Failure: Diagnosis and Management.

Acute liver failure is life threatening liver injury with coagulopathy and hepatic encephalopathy within 26 weeks and generally, in the absence of preexisting liver disease. Fulminant liver failure occurs when hepatic encephalopathy occurs within 8 weeks of jaundice. The majority of patients with ALF are women with the median age of 38 years. In the United States, drug induced liver injury including acetaminophen causes the majority of ALF cases. The etiology of ALF should be determined, if possible, because many causes have a specific treatment. The mainstay for ALF is supportive care and liver transplantation, if necessary. There are multiple prognostic criteria available. Prognosis can be poor and patients should be referred to a liver transplantation center as soon as possible.

Increased serum levels of regenerative miRNAs in patients with spontaneous recovery from acute liver failure

Introduction: Acute liver failure (ALF) represents a life-threatening situation characterized by sudden and massive liver cell death in the absence of preexisting liver disease. Although most patients require liver transplantation to prevent mortality, some recover spontaneously and show complete liver regeneration. The molecular mechanisms of spontaneous recovery from ALF and the role of miRNAs are largely unknown. We therefore investigated miRNAs such as miR-21 and miR-221, which have been implicated to play a role in liver regeneration, in sera of ALF patients with or without spontaneous recovery. In addition, we analyzed growth-inhibitory target genes of those miRNAs as well as hepatocyte proliferation in liver tissues of spontaneously recovered and non-recovered ALF patients.

MicroRNAs play a role in spontaneous recovery from acute liver failure.

Acute liver failure (ALF) represents a life-threatening situation characterized by sudden and massive liver cell death in the absence of preexisting liver disease. Although most patients require liver transplantation to prevent mortality, some recover spontaneously and show complete liver regeneration. Because of the rarity of this disease, the molecular mechanisms regulating liver regeneration in ALF patients remain largely unknown. In this study, we investigated the role of microRNAs (miRs) that have been implicated in liver injury and regeneration in sera from ALF patients (n = 63). Patients with spontaneous recovery from ALF showed significantly higher serum levels of miR-122, miR-21, and miR-221, compared to nonrecovered patients. In liver biopsies, miR-21 and miR-221 displayed a reciprocal expression pattern and were found at lower levels in the spontaneous survivors, whereas miR-122 was elevated in both serum and liver tissue of those patients. As compared to nonrecovered patients, liver tissue of spontaneous survivors revealed not only increased hepatocyte proliferation, but also a strong down-regulation of miRNA target genes that impair liver regeneration, including heme oxygenase-1, programmed cell death 4, and the cyclin-dependent kinase inhibitors p21, p27, and p57. Our data suggest that miR-122, miR-21, and miR-221 are involved in liver regeneration and might contribute to spontaneous recovery from ALF. Prospective studies will show whether serological detection of those miRNAs might be of prognostic value to predict ALF outcome.

Significant advances towards a reproducible, clinically relevant large animal model of acetaminophen‐induced acute liver failure

Acute liver failure (ALF) remains a devastating, life-threatening clinical problem that is defined as sudden hepatocellular necrosis in the absence of pre-existing liver disease. The onset and clinical course of ALF is unpredictable, and despite improved critical care management, mortality remains unacceptably high. Currently, to date, liver transplantation is the only curative treatment. However, owing to the rapid progression of ALF-induced multi-organ failure, and the persistent shortage of available organs, liver transplantation is very limited. Therefore, treatment options to bridge to liver transplantation or to

Fulminant hepatic failure and hepatomegaly caused by diffuse liver metastases from small cell lung carcinoma: 2 autopsy cases

Fulminant hepatic failure (FHF) is defined as a liver disease that causes encephalopathy within 8 weeks of onset in the absence of pre-existing liver disease. Although liver metastases are commonly found in cancer patients, FHF secondary to diffuse liver infiltration is rare. Here, we report the rare autopsy cases of patients with small cell lung carcinoma (SCLC) and secondary FHF. These patients presented with remarkable hepatomegaly and a near complete replacement of the liver parenchyma with metastatic tumor. Neoplastic involvement of the liver should be considered in the differential diagnosis of FHF.

Adult hepatoblastoma: Learning from children

Hepatoblastoma is the most common malignant liver tumour in infants and young children. Its occurrence in the adult population is debated and has been questioned. The aim of this paper is to review the histological and clinical features of adult hepatoblastoma as described in the adult literature, and to compare the findings with those of paediatric hepatoblastoma. The developmental and molecular aspects of hepatoblastoma are reviewed and their potential contribution to diagnosis of adult hepatoblastoma discussed. Case reports of adult hepatoblastoma identified by a PubMed search of the English, French, German, Italian, and Spanish literature through March 2011 were reviewed. Forty-five cases of hepatoblastoma were collected. Age at presentation was variable. Survival was uniformly poor, except for the rare patients who presented with the relatively differentiated, foetal type. The common denominator between adult and paediatric cases is the occurrence of embryonal or immature aspect of the tumours. Whether the adult cases of hepatoblastoma represent blastemal tumours, stem cell tumours, or unusual differentiation patterns in otherwise more frequent adult liver tumours remains to be established. Adult tumours labelled as hepatoblastoma are characterised by malignant appearing mesenchymal components. Surgical management is the cornerstone of therapy in children and also appears to confer an improved prognosis in adults. Whether adult hepatoblastoma exists, remains controversial. Indeed, several features described in adult cases are markedly different from hepatoblastoma as it is understood in children, and other differential diagnoses should also be entertained. Nonetheless, hepatoblastoma should be considered in adults presenting with primary liver tumours in the absence of pre-existing liver disease. Adult and paediatric patients with immature hepatoblastoma appear to have worse outcomes, and adults presenting with presumed hepatoblastoma have an overall poorer prognosis than children with hepatoblastoma. In all patients, surgery should be the treatment of choice, neoadjuvant chemotherapy is advisable.

Acute Liver Failure as a Rare Complication of Metastatic Medullary Thyroid Cancer

Purpose: Acute liver failure (ALF) is characterized by abrupt onset of jaundice, coagulopathy and hepatic encephalopathy in the absence of preexisting liver disease. Medullary thyroid cancer (MTC) is a rare calcitoninsecreting tumor. ALF from metastasis is uncommon and even rarer when it occurs secondary to metastatic MTC. We found no published reports of ALF from metastatic MTC after conducting a systematic search of Medline and Embase. Results: A 59 y.o. male without significant medical history or medication use presented with neck lymphadenopathy. He had no history of alcohol use, smoking or head and neck radiation. CT scan of the neck showed a heterogeneous mass in the right thyroid lobe. Excisional biopsy revealed MTC. Calcitonin was elevated at 4,402 pg/ml, CEA was 9,483 ng/ml. RET gene mutation was negative. In screening for metastasis, abdominal CT showed multiple hypodense liver lesions; the largest was in segment 8 (5.3 x 4.4 cm). Staging PET showed foci of intense FDG uptake in the neck and liver (see Figure), the largest of which corresponded with the same area noted on the CT scan. He underwent tumor debulking and was found to have adjacent muscle and adipose tissue involvement with positive cervical lymph nodes. Prior to planned chemotherapy, he presented with jaundice, fever and encephalopathy. Hematocrit was 38.8%, platelets 91,000/cumm, WBC 22,500/cumm, albumin 2.8 g/dl, direct bilirubin 6 mg/dl, AST 310 u/l, ALT 186 u/l, alkaline phosphatase 335 u/l, INR 2.8, plasma ammonia 128 μmol/L and LDH 920 u/l. Tests for Hepatitis A, B and C, hepatotoxins, autoimmune markers and blood cultures were negative. Ultrasound with doppler noted increased liver heterogeneity, consistent with progression of metastases, but no portal or hepatic vascular occlusion or biliary obstruction. The patient's mental status continued to deteriorate and he expired after progression to hepatic coma, shock and multiorgan failure. Conclusion: Our case suggests metastatic MTC as a rare cause of ALF. The diagnosis of ALF from MTC infiltration is supported by extensive hepatic lesions, persistently elevated calcitonin levels and absence of viral, metabolic or toxicologic etiologies.Figure

How to assess liver function?

The liver comprises a multitude of parenchymal and nonparenchymal cells with diverse metabolic, hemodynamic and immune functions. Available monitoring options consist of 'static' laboratory parameters, quantitative tests of liver function based on clearance, elimination or metabolite formation and scores, most notably the 'model for end-stage liver disease'. This review aims at balancing conventional markers against 'dynamic' tests in the critically ill. There is emerging evidence that conventional laboratory markers, most notably bilirubin, and the composite model for end-stage liver disease are superior to assess cirrhosis and their acute decompensation, while dynamic tests provide information in the absence of preexisting liver disease. Bilirubin and plasma disappearance rate of indocyanine green reflecting static and dynamic indicators of excretory dysfunction prognosticate unfavorable outcome, both, in the absence and presence of chronic liver disease better than other functions or indicators of injury. Although dye excretion is superior to conventional static parameters in the critically ill, it still underestimates impaired canalicular transport, an increasingly recognized facet of excretory dysfunction. Progress has been made in the last year to weigh static and dynamic tests to monitor parenchymal liver functions, whereas biomarkers to assess nonparenchymal functions remain largely obscure.

Caspase activation is associated with spontaneous recovery from acute liver failure

Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration. Because of the low incidence of ALF, however, the molecular mechanisms of liver dysfunction and regeneration are largely unknown. In this study, we investigated the role of apoptosis and caspases in 70 ALF patients using novel biomarkers that allow the detection of caspase activation in serum samples. Compared with healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF revealed a significantly higher activation of caspases than patients that required transplantation or died, although in the latter patients extensive DNA fragmentation and signs of nonapoptotic cell death were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), important cytokines involved in liver regeneration. Our data suggest that caspase activation and apoptosis are involved in ALF of patients with spontaneous recovery, whereas caspase-independent cell death might be more relevant in irreversible forms of liver failure. These findings might be important for therapeutic options of ALF but also suggest that measurement of caspase activation might be of prognostic value to predict the outcome of acute liver failure.

Asymptomatic Liver Mass

Asymptomatic Liver Mass

Liver failure

Liver failure is a rare but life-threatening condition affecting a multitude of other organ systems, most notably the brain and kidneys, following severe hepatocellular injury. Liver failure may develop in the absence ('acute') or presence ('acute-on-chronic') of liver disease with substantial differences in pathophysiology and therapeutic options. Within the last 12 months substantial progress has been made in identifying patients who will potentially benefit from extracorporeal support of their failing liver. In addition to traditional 'static' laboratory tests to assess liver function, the significance of 'dynamic' tests, such as indocyanine green clearance, has been better defined, and these tests are becoming more easily available. Transplantation remains the treatment of choice for fulminant, acute and subacute liver failure with predicted unfavorable outcome according to King's College or Clichy criteria, most notably in the absence of pre-existing liver disease, and should be performed before extrahepatic complications emerge. Encouraging results have been obtained with the use of support systems in patients with acute and acute-on-chronic liver failure in relatively small patient collectives, making well-conducted randomized trials a necessity to define their role in this high-risk population. Current (pre)clinical data suggest that programmed cell death is an important mechanism for the pathogenesis of acute and acute-on-chronic liver failure and, thus, antiapoptotic strategies are promising pharmacologically. Although mortality remains high, substantial progress has been made in 2004 regarding the understanding of pathophysiology, and the monitoring and support of the patient presenting with a failing liver.