Amyloidosis: a rare cause of severe acute liver failure.

Gastrointestinal amyloidosis can be primary, more associated with monoclonal plasma cell dyscrasia, or secondary, usually secondary to a tissue-destructive, chronic inflammatory process (such as inflammatory bowel disease, for example) and long-term dialysis. The rare presentation of severe acute liver failure in systemic amyloidosis can make this diagnosis/ management more difficult. Hepatomegaly with signs of diffuse infiltrative disease and periportal involvement associated with thoracic and other abdominal radiological findings in the appropriate clinical context may constitute a diagnostic imaging clue in this challenge.

Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants.

We report the clinical, biochemical and genetic findings from a Spanish boy of Caucasian origin who presented with fever-dependent RALF (recurrent acute liver failure) and osteogenesis imperfecta (OI). Whole-exome sequencing (WES) uncovered two compound heterozygous variants in NBAS (c.[1265 T > C];[1549C > T]:p.[(Leu422Pro)];[(Arg517Cys)]), and a heterozygous variant in P4HB (c.[194A > G];[194=]:p.[(Lys65Arg)];[(Lys65=)]) that was transmitted from the clinically unaffected mother who was mosaic carrier of the variant. Variants in NBAS protein have been associated with ILFS2 (infantile liver failure syndrome-2), SOPH syndrome (short stature, optic nerve atrophy, and Pelger-Huët anomaly syndrome), and multisystem diseases. Several patients showed clinical manifestations affecting the skeletal system, such as osteoporosis, pathologic fractures and OI. Experiments in the patient's fibroblasts demonstrated that mutated NBAS protein is overexpressed and thermally unstable, and reduces the expression of MGP, a regulator of bone homeostasis. Variant in PDI (protein encoded by P4HB) has been associated with CLCRP1 (Cole-Carpenter syndrome-1), a type of severe OI. An increase of COL1A2 protein retention was observed in the patient's fibroblasts. In order to study if the variant in P4HB was involved in the alteration in collagen trafficking, overexpression experiments of PDI were carried out. These experiments showed that overexpression of mutated PDI protein produces an increase in COL1A2 retention. In conclusion, these results corroborate that the variants in NBAS are responsible for the liver phenotype, and demonstrate that the variant in P4HB is involved in the bone phenotype, probably in synergy with NBAS variants.

Hydrogen peroxide-activatable polymeric prodrug of curcumin for ultrasound imaging and therapy of acute liver failure.

Curcumin is a major active phenolic component of turmeric and has gained great attention in pharmaceutics due to its potent antioxidant, anti-inflammatory and anticancer activity. Here, we developed poly(oxalate-co-curcumin) (POC) as a hydrogen peroxide (H2O2)-activatable polymeric prodrug of curcumin by incorporating curcumin in the backbone of H2O2-responsive polyoxalate. POC particles effectively scavenged H2O2 and released curcumin in a H2O2-triggered manner. POC particles exhibited excellent antioxidant and anti-inflammatory activity in activated cells. POC particles intravenously administrated into acetaminophen-intoxicated mice remarkably suppressed the level of alanine transaminase and inhibited apoptotic cell death in liver. Interestingly, POC particles could also enhance the ultrasound contrast in the intoxicated liver due to CO2 bubble generation through H2O2-triggered oxidation of peroxalate esters. Given their H2O2-responsiveness and highly potent antioxidant activity, POC particles hold great translational potential as theranostic agents for H2O2-associated diseases.

Substantial hepatic necrosis is prognostic in fulminant liver failure.

AIM: To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation. The patients were grouped based on the etiology of hepatic necrosis. Each of the etiology groups were then further stratified according to whether or not they had received a liver transplant post-index biopsy, and whether or not the patient survived. RESULTS: The core tissue length ranged from 5 to 44 mm with an average of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced liver injury (DILI), 9 hepatitis virus infection, and 4 unknown origin. Among them, 11 showed submassive (26%-75% of the parenchymal volume) and 26 massive (76%-100%) necrosis. Transplant-free survival was worse in patients with a higher extent of necrosis (40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%-75% and 26%-50%, respectively). Additionally, transplant-free survival rates were 66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively. Even after liver transplantation, the survival rate in patients as a result of viral hepatitis remained the lowest (80%, 100%, and 40% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively). CONCLUSION: Adequate liver biopsy with more than 75% necrosis is associated with significant transplant-free mortality that is critical in predicting survival.

Diagnostic utility of radiological heterogeneity in acute severe (fulminant) autoimmune hepatitis.

BACKGROUND: Histological examination is useful for the diagnosis of acute severe (fulminant) autoimmune hepatitis (AIH), but it is sometimes difficult to perform liver biopsy due to the complicated coagulopathy and ascites. We have shown that heterogeneous hypoattenuation on unenhanced computed tomography (CT) is a characteristic imaging feature of acute severe (fulminant) AIH. In the present study, we examined the utility of the imaging feature by applying the score to diagnose acute severe (fulminant) AIH. METHODS: Twenty-three patients with acute severe (fulminant) AIH were analyzed retrospectively. Modified AIH score was created by adding three points to AIH score with/without histological points in case of the presence of heterogeneous hypoattenuation on unenhanced CT. RESULTS: Areas of hypoattenuation were present in 15 (65%) patients, all of which were heterogeneous pattern. Five (22%) patients were diagnosed as "definite" AIH, 16 (69%) as "probable" and two (9%) as "non-diagnosis" by the revised original score without histological score. By adding three points, two of "non-diagnosis" changed to "probable" AIH, and all patients were diagnosed as AIH. CONCLUSIONS: Modified AIH score using heterogeneous CT image finding would be beneficial especially for patients in whom histological examinations cannot be performed because of complications.

Hepatitis A virus genotype IA-infected patient with marked elevation of aspartate aminotransferase levels.

We describe a case of acute liver failure (ALF) without hepatic encephalopathy with marked elevation of aminotransferase due to hepatitis A, according to the revised Japanese criteria of ALF. This liver biopsy of the patient showed compatible to acute viral hepatitis and she immediately recovered without intensive care. She had no comorbid disorders. Of interest, phylogenetic tree analysis using almost complete genomes of hepatitis A virus (HAV) demonstrated that the HAV isolate from her belonged to the HAV subgenotype IA strain and was similar to the HAJFF-Kan12 strain (99% nucleotide identity) or FH1 strain (98% nucleotide identity), which is associated with severe or fulminant hepatitis A. Careful interpretation of the association between HAV genome variations and severity of hepatitis A is needed and the mechanism of the severe hepatitis should be explored.

Fulminant hepatic failure secondary to acyclovir-resistant herpes simplex virus.

Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase. Acyclovir is a first-line therapy for HSV infection; however, acyclovir-resistant viral strains should be considered and alternative HSV therapies given in HCT recipients whose HSV infection does not improve on acyclovir therapy.

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis.

OBJECTIVE: To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL). MATERIALS AND METHODS: BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASHTM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging. RESULTS: The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min-1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining. CONCLUSIONS: Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

Acute liver failure secondary to hepatic compartment syndrome: case report and literature review.

We report a case of a patient with a delayed large intrahepatic hematoma and transient decline in hemoglobin to 62 g/L 18 days after liver injury. Abdominal computed tomography revealed seriously flattening of inferior vena cava, which was consistent with compression by the enlarging hematoma. Although traditionally there was no indication for surgical intervention, the patient developed acute liver failure with a progressive increase in liver enzymes and bilirubin. We postulated the ever-expanding hematoma might have led to dramatically elevated intrahepatic pressures that in turn restricted hepatic vein reflux and subsequently resulted in acute liver failure. Therefore, she underwent percutaneous drainage, and the decompression instantly reversed the liver injury. This phenomenon is similar to the well-described abdominal compartment syndrome, which is defined as new onset organ dysfunction or failure secondary to sustained intraabdominal hypertension and in which decompression is the standard treatment.

Unique morphologic and clinical features of liver predominant/primary small cell carcinoma--autopsy and biopsy case series.

Liver predominant small cell carcinoma is rare but often presents as hyperacute liver failure with unknown primary and is a medical emergency. We present 2 autopsy and 7 biopsy cases of liver predominant small cell carcinoma and demonstrate that these patients present with liver failure and identifiable hepatomegaly but lack discrete lesions on imaging as well as no mass lesions identified in other organs including lung. Compared with the multiple nodules of metastatic small cell carcinoma in the liver, unique morphologic feature of liver predominant/primary small cell carcinoma in autopsy and biopsy specimens was a diffuse infiltration of small blue neoplastic cells predominantly in the sinusoidal space in the liver parenchyma. Before diagnosing liver predominant/primary small cell carcinoma, other infiltrating small blue cell neoplasms including lymphoma and peripheral neuroectodermal tumor need to be ruled out through immunohistochemistry. We, therefore, demonstrate that liver biopsy together with a rapid panel of immunostains is necessary to firmly establish a diagnosis of liver predominant small cell carcinoma and allow clinicians to immediately implement potentially lifesaving chemotherapy.

MDCT of abdominopelvic oncologic emergencies.

Acute complications arising in abdominopelvic malignancies represent a unique subset of patients presenting to the emergency room. The acute presentation can be due to complications occurring in the tumor itself or visceral or vascular structures harboring the tumor. Multidetector computed tomography (MDCT) is the investigation of choice in the workup of these patients and enables appropriate and timely management. Management of the complication depends primarily on the extent of the underlying malignancy and the involvement of other viscera. The purpose of this article is to depict the imaging features of these complications on MDCT.

Angiosarcoma of the liver as a cause of fulminant liver failure.

Primary liver sarcomas make up 2% of all malignant neoplasms of the liver; of these, angiosarcoma is the most common type. Primary liver tumours rarely cause fulminant hepatic failure (FHF), which is most frequently caused by non-neoplasmic pathologies. In the case of neoplasms, the most frequent are lymphoma and metastatic carcinomas. We describe the case of a 76-year-old man who suffered from FHF as a result of a liver angiosarcoma and we present a review of the medical literature in which we found only two cases of liver angiosarcomas linked to FHF.

Fulminant hepatic failure caused by adenovirus infection mimicking peliosis hepatitis on abdominal computed tomography images after allogeneic hematopoietic stem cell transplantation.

Disseminated adenovirus disease after allogeneic hematopoietic stem cell transplantation (HSCT) is lethal in most cases, especially when it develops as fulminant hepatic failure. We encountered a patient who developed fulminant hepatic failure caused by adenovirus infection. She did not show manifestations of graft-versus-host disease and the results of serum tests for viral infection were all negative. Abdominal computed tomography (CT) findings were consistent with peliosis hepatitis. She died of fulminant hepatic failure, however, and pathological examinations of the liver specimen obtained after her death revealed adenovirus infection. In this report, we review the clinical characteristics and imaging findings of fulminant hepatic failure caused by adenovirus infection.

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report.

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.

Percutaneous treatment of liver failure and acute mesenteric ischaemia.

INTRODUCTION: Synchronous embolism to the superior mesenteric artery (SMA) and coeliac axis (CA) is a rare disease. REPORT: A 67-year-old man with atrial fibrillation developed acute liver failure due to an embolic occlusion of the CA and SMA, with a severe coagulation disorder. He was successfully managed with percutaneous stent placement and an exploratory laparotomy was not needed. He remains symptom-free 1 year after the procedure, and duplex follow-up showed stent patency. CONCLUSION: Endovascular techniques in patients with liver failure, no signs of peritonism, early diagnosis and high operative risk seem feasible and should be used if possible, as first-line option.

Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram: a case report.

A 54-year-old woman with hepatic encephalopathy grade IV (coma) and flat electroencephalogram (EEG) due to fulminant liver failure (FHF) due to hepatitis B virus infection was admitted to our hospital on May 24, 2002. We performed a living donor auxiliary partial orthotopic liver transplantation (APOLT) emergently on the day of admission. The donor was the patient's son, whose ABO blood group was identical. The immunosuppressant regimen consisted of tacrolimus and low-dose steroids. The left lobe (260 g) of the recipient, which was removed using a Pringle maneuver, was reconstructed with a left lobe (417 g) graft from the donor, which was orthotopically positioned as an auxiliary support. The patient remained in a coma for the first 5 days but on day 6 her eyes opened and followed objects. Finally, she recovered an almost normal appearance. Abdominal compartment syndrome, bile leak, and a mild rejection episode occurred during the postoperative course; all were treated successfully. The patient was discharged on the postoperative day 142. Computed tomography (CT) scan and biopsy were used to follow the changes in the graft and the native liver. On postoperative day 520, a CT scan showed a remarkable improvement in native liver size (493 cm3). Immunosuppression was tapered off and stopped on the postoperative day 635 to surrender the grafted liver. The graft liver biopsy specimen showed severe chronic rejection. The present status of the patient, who is now more than 7 years after transplantation, is an absence of neurological findings with normal liver function.

Transjugular biopsy of an atypical focal nodular hyperplasia in a patient with acute liver failure clinical presentation.

The following is a report on one case of successful biopsy of a hepatic focal lesion incidentally found in an emergency computed tomography scan performed in a patient with acute liver failure clinical presentation. The presence of peri-hepatic ascites and severe coagulopathy contraindicated the percutaneous biopsy. The transjugular approach was used to perform a random liver biopsy to assess the amount of hepatic necrosis and to perform the focal lesion biopsy orienting the needle with sonography guidance. The specimen acquired was satisfactory to exclude the presence of malignant cells in the lesion; the diagnosis of atypical focal nodular hyperplasia was performed. The patient underwent successful liver transplantation the day after.

[Evaluation of liver function before living donor liver transplantation and liver resection]. / A májfunkció kiértékelése élo donoros májátültetést és májreszekciót megelozoen.

UNLABELLED: Liver resection is the curative therapeutic option for hepatocellular carcinoma, biliary tumors, metastases of colorectal and other extrahepatic tumors, living donor liver transplantation and other benign liver diseases. AIM OF STUDY: To summarize the evaluation methods of liver function before living donor liver transplantation and liver resection. METHOD: We summarize the literature about the evaluation of liver function. RESULTS: Perioperative mortality is determined mostly by the extent of preoperative evaluation focused on the liver. After resection the remnant liver parenchyma must cope with the challenge caused by increased metabolism, portal overflow, decreased vascular bed and biliary tract and oxidative stress following the operation. If the remnant liver is unable to grow up to this challenge, acute liver failure occurs. This maintains the necessity of determining the hepatic functional reserve and the hepatic remnant volume. Child-Pugh classification is widely spread to predict outcome. Dynamic functional tests such as indocyanine green retention test, galactosyl human serum albumin scintigraphy and aminopyrine breath tests can be used to evaluate hepatic reserve. To determine remnant liver volume modern imaging processes such as CT volumetry and hepatobiliary scintigraphy are available. CONCLUSION: After the detailed evaluation resection can be limited to an extent which is oncologically radical enough (1% remnant liver tissue/kg) and spares parenchyma which can ensure survival yet. With careful preoperative examination mortality can be reduced even to reach zero.