Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report

BACKGROUND Light chain(AL)amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells,which leads to progressive dysfunction of the affected organs.The two most commonly affected organs are the heart and kidneys,and liver is rarely the dominant affected organ with only 3.9%of cases,making them prone to misdia-gnosis and missed diagnosis.CASE SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly.Initially,based on enhanced computed tomography scan and angiography,Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed.However,addi-tional diagnostic procedures,including liver biopsy and bone marrow-exami-nation,revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression.The disease course was progre-ssive and fatal,and the patient eventually died 5 mo after initial presentation of symptoms.CONCLUSION AL amyloidosis with isolated liver involvement is very rare,and can be easily misdiagnosed as a vascular disease.

Liver transplantation for polycystic liver and massive hepatomegaly

Liver tumor and other benign liver diseases such as polycystic liver disease can cause massive hepatomegaly and may represent an indication for liver transplantation(LT)in some instances.In this setting,LT can be extremely difficult and challenging due to its decreased mobility and access to vascular supply.Benefit from either a right or a left partial liver resection during the transplant procedure has been advocated to safely accomplish the hepatectomy of the native liver.Although we believe that partial hepatectomy adds some risk to intra-operative bleeding,we alternatively advise a different approach.We have a successful experience with LT in 6 massive hepatomegaly patients due to giant liver lesions.All the transplant procedures were performed without intermediate partial liver resection,showing that selective use of veno-venous bypass can play a significant role in the treatment of massive hepatomegaly.

Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective:To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus(FSS)and Schisandra chinensis Fructus(FSC)oils in mice.Methods:Mice were orally administered a single dose of SchisandraeFructusoils.Serumandhepatictriglyceride(TG),triglyceridetransferprotein(TTP),apolipoproteinB48(Apo B48),very-low-densitylipoprotein(VLDL),hepatocytegrowth factor(HGF),alanine aminotransfease(ALT)and liver index were measured at 6-120 h post-dosing.Results:FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels,with maximum increases in the liver(by 297%and 340%)at 12 h post-dosing and serum(244%and 439%)at 24-h post-dosing,respectively.Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51%and63%,Apo B48 by 152%and 425%,and VLDL by 67%and 38%in mice,respectively.FSS and FSC oil treatments also increased liver mass by 53%and 55%and HGF by 106%and 174%,but lowered serum ALT activity by 38%and 22%,respectively.Fenofibrate pre/co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41%and 49%at 48 h post-dosing,respectively,but increased hepatic TG contents(by 38%and 33%,respectively)at 12 h post-dosing.Conclusions:Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil(mainly increasing endogenous TG)and FSC oil(mainly elevating exogenous TG).

Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway

Fenofibrate,a peroxisome proliferator-activated receptor α(PPARα)agonist,is widely prescribed for hyperlipidemia management.Recent studies also showed that it has therapeutic potential in various liver diseases.However,its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear.Here,the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice,which was dependent on hepatocyteexpressed PPARα.Yes-associated protein(YAP)is pivotal in manipulating liver growth and regeneration.We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination,promoting its K63-linked ubiquitination,and enhancing the interaction and transcriptional activity of the YAP-TEAD complex.Pharmacological inhibition of YAP-TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly.Other factors,such as MYC,KRT23,RAS,and RHOA,might also participate in fenofibrate-promoted hepatomegaly and liver regeneration.These studies demonstrate that fenofibratepromoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling,with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

Epidemiological, Clinical and Etiological Aspects of Adult Hepatomegaly at the Gabriel Touré University Hospital of Bamako in 2023

Summary: Hepatomegaly is one of the clinical signs commonly encountered in chronic liver disease. The aim of our study was to study the epidemiological, clinical and etiological aspects of hepatomegaly in the hepato-gastroenterology department (HGE) of the Gabriel Touré university hospital. This was a cross-sectional study that took place from September 2021 to October 2022 in the department. All patients aged 18 years and older with hepatomegaly, hospitalized or examined by physicians were included. We collected 100 cases of hepatomegaly, representing 3.7% of 2661 patients examined or hospitalized in the HGE department during the study period. These patients had a mean age was 46.7 ± 16.10 years with extremes of 18 and 76 years. The sex ratio was 2.7. Jaundice was the most commonly reported history with a frequency of 26%. Pertaining to patients’ lifestyle, alcohol consumption was the most common feature with 6%. The most common associated clinical signs were jaundice, ascites, and edema of the lower limbs. Painful hepatomegaly (86%), with a sharp lower edge (74%), a firm consistency (69%), and an irregular surface (52%) was frequently observed. Cytolysis (75.5%), increased alphafetoprotein levels (70%), microcytic anemia (37%), hyperleukocytosis (54.3%), and biological hepatocellular insufficiency syndrome (low albumin with 30.4%, high bilirubinemia with 61.2% and low platelets with 33.9%) were the most common observed laboratory abnormalities. Hepatitis B virus markers (61%) were the most frequently found in the study patients. At ultrasound examination, heterogeneous hepatomegaly was observed in 87.3% of the patients. Esophageal varices (43.1%) were more commonly seen than other varices during upper gastrointestinal endoscopy. The dominant etiology was hepatocellular carcinoma on cirrhosis with 66% followed by cirrhosis. Conclusion: Painful hepatomegaly was quite frequently in our urban setting hospital with several etiologies. HCC was the most common etiology, therefore measures to prevent it in the community need to be established by the concerned stakeholders to improve adult population health in Bamako.

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially via yes-associated protein activation

The constitutive androstane receptor(CAR, NR3 I1) belongs to nuclear receptor superfamily.It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein(YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration.TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wildtype(WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy(PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice.Hepatocytes enlargement around central vein(CV) area was observed, meanwhile hepatocytesproliferation was promoted as evidenced by the increased number of KI67+cells around portal vein(PV)area. The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation. Co-immunoprecipitation results suggested a potential proteineprotein interaction of CAR and YAP. However, CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient(Yape/e) mice. In summary, CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway, which provides new insights to further understand the physiological functions of CAR.

Liver involvement in patients with COVID-19 infection:A comprehensive overview of diagnostic imaging features

During the first wave of the pandemic,coronavirus disease 2019(COVID-19)infection has been considered mainly as a pulmonary infection.However,different clinical and radiological manifestations were observed over time,including involvement of abdominal organs.Nowadays,the liver is considered one of the main affected abdominal organs.Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs.After clinical assessment,radiology plays a key role in the evaluation of liver involvement.Ultrasonography(US),computed tomography(CT)and magnetic resonance imaging(MRI)may be used to evaluate liver involvement.US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection,in particular liver steatosis and portal-vein thrombosis.CT and MRI are used as second-and third-line techniques,respectively,considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization.This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.

Niemann-Pick A/B Disease in a 13-Year-Old Child and Review of the Literature

Niemann-Pick disease (NPD) refers to a group of patients who have varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features, including hepatosplenomegaly, insufficiency pulmonary and/or central nervous system (CNS). Thanks to the pioneering work of Roscoe Brady and colleagues, we now know that there are two distinct metabolic abnormalities that explain NPD. The first is due to the deficient activity of the acid sphingomyelinase enzyme (ASM;NPD “types A and B”), and the second is due to defective functioning in the transport of cholesterol (NPD “type C”). We report the case of a 13-year-old adolescent diagnosed with Niemann-Pick A/B disease.

Autophagy and ethanol-induced liver injury

The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

Glycogenic hepatopathy:A narrative review

Glycogenic hepatopathy(GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease(NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.

Case of autoimmune hepatitis with markedly enlarged hepatoduodenal ligament lymph nodes

Autoimmune hepatitis(AIH) is a necroinflammatory liver disease of unknown etiology.The disease is characterized histologically by interface hepatitis,biochemically by increased aspartate aminotransferase and alanine aminotransferase levels,and serologically by increased autoantibodies and immunoglobulin G levels.Here we discuss AIH in a previously healthy 37-year-old male with highly elevated serum levels of soluble interleukin-2 receptor and markedly enlarged hepatoduodenal ligament lymph nodes(HLLNs,diameter,50 mm).Based on these observations,the differential diagnoses were AIH,lymphoma,or Castleman's disease.Liver biopsy revealed the features of interface hepatitis without bridging fibrosis along with plasma cell infiltration which is the typical characteristics of acute AIH.Lymph node biopsy revealed lymphoid follicles with inflammatory lymphocytic infiltration;immunohistochemical examination excluded the presence of lymphoma cells.Thereafter,he was administered corticosteroid therapy:after 2 mo,the enlarged liver reached an almost normal size and the enlarged HLLNs reduced in size.We could not find AIH cases with such enlarged lymph nodes(diameter,50 mm) in our literature review.Hence,we speculate that markedly enlarged lymph nodes observed in our patient may be caused by a highly activated,humoral immune response in AIH.

Is dengue emerging as important cause of acute liver failure in endemic regions?

Dengue virus infection continues to be major public health problem in large part of world.The epidemiology of dengue viral infection is becoming increasingly complex and has substantially changed over almost past six decades not only in terms of prevalent strains and geographical locations but also in terms of disease severity and atypical presentations.Though liver is the most common organ affected but is generally asymptomatic.We present a case of infant with severe dengue who died of fulminant hepatic failure and showed pan lobular necrosis on post mortem liver biopsy.The case is being presented to highlight life threatening complication of dengue in young children,and dengue viral infection as a cause of acute liver failure in endemic areas.Thus dengue fever should also be considered as one of the differential diagnosis in children presenting with fever and fulminant hepatic failure in endemic regions.

Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Hepatic glycogenosis(HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder(with circulating aminotransferase increase) in the presence of poor glycemic control(elevation of glycated hemoglobin, Hb A1 c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage(infectious, metabolic, obstructive and autoimmune disease). The imaging study(ultrasonography and/or radiological examinations) gives information about the liver alterations(hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usu-ally accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options(transplantation) have been successfully reported.

An unusual case of aggressive systemic mastocytosis mimicking hepatic cirrhosis

Hepatic involvement in aggressive systemic mastocytosis(ASM) is relatively common, and the main clinical features of this disease include hepatomegaly, portal hypertension, ascites, and fibrosis. Cirrhosis is a rare ASM symptom. We report an ASM case that initially mimicked cirrhosis based on clinical and radiographic analyses. The portal tract was expanded by mononuclear inflammatory cells, and an increase in collagen amount was observed in routine histological sections of the biopsied liver. A diagnosis of systemic mastocytosis(SM) was made after ancillary tests for mast cells using bone marrow aspirates. Extensive involvement of the liver and gastrointestinal tract was observed. Clinicians and pathologists need to consider ASM as a diagnosis or differential diagnosis in a clinical case of cirrhosis with unknown etiology. The diagnosis can be confirmed or disregarded by immunohistochemical staining and molecular analysis.

Epidemiological, Clinical, Paraclinical, Etiological and Therapeutic Aspects of Liver Cirrhosis in the Hepato-Gastroenterology Department of the Hospital Aristide Le Dantec in Dakar

Introduction: Liver cirrhosis is a global public health issue. Our aim was to determine the epidemiological, clinical, paraclinical and therapeutic aspects of liver cirrhosis in the hepato-gastroenterology department of the hospital Aristide Le Dantec in Dakar. Patients and Methods: We conducted a retrospective study with a descriptive focus covering the period from January 1st, 2010 to December 31, 2020. We included the medical records of patients which presented body of clinical and paraclinical arguments which supported the diagnosis of cirrhosis. The data collected were related to age, gender, clinical, paraclinical, therapeutic and prognosis aspects of cirrhosis and were analyzed with the software Sphinx Plus. Results: Prevalence of cirrhosis was 6.2%. Sex ratio was 2.1%. The average age was 38 years. Asthenia (60.9%), altered performance status (60.1%), abdominal pain (37.2%), gastrointestinal bleeding (29.6%) and abdominal swelling (27.8%) were the most common motives of consultation. Physical examination revealed primarily portal hypertension (74.9%), liver failure (2.4%), hepatomegaly (28.2%) and anemia (13.7%). Viral hepatitis B was the most common etiology (81.9%). Abdominal screening (ultrasound/CT scan) showed hepatomegaly (80.6%), liver dysmorphia (87.7%), portal hypertension signs (85.3%) and portal vein thrombosis (18.2%). 55.1% Patients were classified as Child Pugh A, 33.8% were Child Pugh B and 11.1% were Child Pugh C. Tenofovir Disoproxil Fumarate (TDF) was prescribed to all patients affected by hepatitis B virus only. Evolution was characterized by clinical improvement and prognosis reclassification. Conclusion: Liver cirrhosis is a frequent pathology in the hepato-gastroenterology department of the hospital Aristide Le Dantec in Dakar. It affects young male adult. Hepatitis B virus is the leading cause. TDF is an effective treatment.

Hepatic Solitary Fibrous Tumor Presenting as Severe Hypoglycaemia: A Case-Report

We report a case of a patient presenting with profound insulin-independent hypoglycaemia. A large hepatic leasion was identified and surgically resected. Histology confirmed a 17.5 cm hepatic solitary fibrous tumour. The clinical and biochemical presentation is consistent with IGF-II mediated hypoglycaemia.

CT-Scan Findings of Hepatic Mass Patients Attending at a Tertiary Care Hospital in Bangladesh

Background: CT-scan is a very useful diagnostic tool for the detection of hepatic mass. Objective: The present study was undertaken to determine the CT-scan findings of benign and malignant hepatic mass patients. Methodology: This was a cross sectional study conducted in Radiology and Imaging Department at Mymensingh Medical College Hospital (MMCH), Mymensingh;Dhaka Medical College Hospital (DMCH), Dhaka and Banghabandhu Sheikh Mujib Medical University (BSMMU), Dhaka with the collaboration of Pathology Department of the same institute for histopathological confirmation. This study was carried out from January 2006 to December 2007 for a period of 2 years. The patients who were clinically suspected of having hepatic mass attended in the Radiology and Imaging Department in the above mentioned institutes were included as study population. All the CT-scan findings were recorded. Result: A total number of 50 patients were enrolled for this study. CT-scan was done among 40 males and 10 females with a mean age of 51.28 years old. Hypodensity was found in 17 (60.7%) and 18 (81.8%) cases in malignant and benign hepatic lesions respectively. Ill-defined margin was detected in 12 (42.9%) and 6 (27.3%) cases respectively. Calcification was present on 11 (39.3%) malignant lesion and 6 (27.3%) benign lesions. Pressure effect on biliary apparatus was found in 11 (39.3%) malignant lesions and 1 (4.5%) benign lesions (p < 0.05). Lymphadenopathy was found in 10 (35.7%) malignant lesions and 1 (4.5%) benign lesions (p < 0.05). Conclusion: In conclusion, CT-scan findings of malignant and benign hepatic mass show hypodensity with more contrast enhancement in malignant lesions with more calcification in malignant lesion;however, significant difference is detected in pressure effect on biliary apparatus and lymphadenopathy.

Ypel5 regulates liver development and function in zebrafish

YPEL5 is a member of the Yippee-like(YPEL)gene family that is evolutionarily conserved in eukaryotic species.To date,the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models.Here,using CRISPR/Cas9-mediated genome editing,we generated a stable ypel5^(−/−)mutant zebrafish line.Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation.Meanwhile,hepatic metabolism and function are dysregulated in ypel5^(−/−)mutant zebrafish,as revealed by metabolomic and transcriptomic analyses.Mechanistically,Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5.Zebrafish hnf4a overexpression could largely rescue ypel5 deficiencyinduced hepatic defects.Furthermore,PPARαsignaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene.Herein,this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Patients with severe schistosomiasis mansoni in Ituri Province, Democratic Republic of the Congo

Background:Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas.These complications are rarely reported and,hence,underestimated.Case presentation:We report on eight patients with severe morbidity associated with S.mansoni infection in Ituri Province,northeastern Democratic Republic of Congo(DRC).The patients were identified during a community-based survey in 2017;one patient was seen at the district hospital.After taking the patients'history,a clinical examination and an abdominal ultrasonographical examination were performed.S.mansoni infection was diagnosed in fecal(Kato-Katz technique)and urine(point-of-case circulating cathodic antigen test)samples.These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high 5.mansoni infection prevalence and related morbidity.The patients'ages ranged from 19 to 57 years;four patients were women.Three patients reported hematemesis.Two patients were severely anemic.All patients reported non-specific abdominal symptoms,such as diarrhea(six patients),abdominal pain(seven patients),and blood in the stool(five patients),as well as weight loss(two patients).Abdominal ultrasonography revealed ascites in four patients.All patients had portal hypertension with hepatomegaly(seven patients)or splenomegaly(five patients).Of the six patients with a discernable liver parenchyma pattern,five displayed pattern F and three patient displayed pattern E.Liver parenchyma was not visible for two patients with severe ascites.An 5.mansoni infection was confirmed in six patients,with infection intensity ranging from light to heavy.All S.mansoni positive patients were treated with praziquantel(40 mg/kg body weight)and referred to the district hospital for follow-up.One patient with severe ascites died two weeks after we saw her.Due to security and accessibility reasons,the villages could not be visited again and the patients were lost to follow-up.Conclusions:Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S.mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications.