Gynura root induces hepatic veno-occlusive disease:A case report and review of the literature

Gynura root has been used extensively in Chinese folk medicine and plays a role in promoting microcirculation and relieving pain.However,its hepatic toxicity should not be neglected.Recently,we admitted a 62-year old female who developed hepatic veno-occlusive disease(HVOD)after ingestion of Gynura root.Only a few articles on HVOD induced by Gynura root have been reported in the literature.It is suspected that pyrrolizidine alkaloids in Gynura root might be responsible for HVOD.In this paper,we report a case of HVOD and review the literature.

A case report of hepatic veno-occlusive disease after ingesting dainties

Hepatic veno-occlusive disease (HVOD) is rarely encountered and easily misjudged as Budd-Chiari syndrome. It is often related to stem cell transplantation in recent years. We report a case of HVOD that is related to ingestion of some palatable local dishes. The diagnosis was confirmed by liver biopsy pathology with specific observation of inflammatory changes and fibrosis of venules intima, dilated sinusoids and central veins. Chronic diarrhea is unique for this case as a result of ingesting harmful stuffs. This case demonstrated that supervision and instruction of food recipe and traditional medicine are crucial, and prompt diagnosis, supportive care and specific treatment are essential to decreasing the morbidity and mortality of HVOD.

Hepatic veno-occlusive disease induced by Gymura segetum: report of two cases

BACKGROUND: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is associated with a high mortality because of its severity. Gymura segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in rural areas in China. This study was undertaken to better understand VOD and its relations to the effect of Gymura segetum. METHODS: Between 2000 and 2002,two patients were admitted to our department because of VOD. Before admission, both of them had been injured and taken oral decoction of patent drug Gymura segetum. We analyzed the clinical manifestations, diagnosis and therapy of the two patients. RESULTS: Pyrrolizidine in Panax notginseng was proved to induce VOD. The diagnosis of VOD depended on hepatic biopsy. CONCLUSION: Gymura segetum can induce VOD. More attention should be paid to its unsuscepted side effects.

Reliable experimental model of hepatic veno-occlusive disease caused by monocrotaline

BACKGROUND:Hepatic veno-occlusive disease(HVOD)is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids.Many experimental models were established to study its mechanisms or therapy,but few are ideal.This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease. METHODS:Thirty-two male rats were randomly classified into 5 groups,and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg).They were sacrificed on day 7(groups A,B and D)or day 10(groups C and E).Blood samples were collected to determine liver enzyme concentrations.The weight of the liver and body and the amount of ascites were measured.Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system.The positivity of proliferating cell nuclear antigen(PCNA)was estimated. RESULTS:The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths)and the histopathological picture of HVOD.On the other hand,the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations.Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased,especially that of hepatocytes.CONCLUSIONS:Monocrotaline induces acute,dose- dependent HVOD in rats.The model is potentially reversible with a low dose,but reliable and irreversible with a higher dose.The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD.The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies

Hepatic veno-occlusive disease(VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.

Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease(VOD) in non-adult patients undergoing hematopoietic stem cell transplantation(HSCT) during cyclosporine therapy.METHODS: A total of 123 patients taking cyclosporinewere evaluated using an electronic medical system at the Seoul National University Children's Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions(ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease(a GVHD) and VOD. Although the incidences of a GVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level(BILmax) of ≥ 1.4 mg/d L correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/d L, suggestive of more sensitive VOD indication in this age group.

One patient of hepatic veno-occlusive disease with an increased cancer antigen-125 expression caused by misuse of Sedum aizoon

Nowadays hepatic veno-occlusive disease is mainly caused by Sedum aizoon in China,and its prognosis dependents on the dosage and courses of the Sedum aizoon treatment but lacks other objective indicators.There are a lot relationships between CA125 level and liver cirrhosis,this case had a obvious increased CA125 level in the serum,hydrothorax and ascites,following by the liver cirrhosis in a short time,and then died of upper gastrointestinal bleeding.By now we guess that CA125 level could forecast the liver cirrhosis following by hepatic veno-occlusive,which will become the prognosis of the hepatic veno-occlusive.

Vacuum therapy prevents corporeal veno-occlusive dysfunction and penile shrinkage in a cavernosal nerve injured rat model

Erectile dysf un ction and penile shri nkage are the comm on complications after radical prostatectomy.Penile rehabilitati on is widely applied after the surgery.Vacuum therapy is one of the three penile rehabilitation methods used in the clinical setting,but its mechanism is not well known.This study was designed to investigate whether vacuum erectile device(VED)can prevent corporeal veno-occlusive dysfunction and penile shrinkage in the bilateral cavernous nerve crush(BCNC)rat model.Adult male Sprague-Dawley rats were randomly assigned into three groups:sham group,BCNC group,and BCNC+VED group.After 4 weeks,penile length and intracavernosal pressure(ICP)were measured,and then the middle part of the penis was harvested after dynamic inf usion caver no sometry to complete the followi ng items:smooth muscle/collage n ratios and collagenⅠ/Ⅲratios;ultramicrostructure of the tunica albuginea,endothelial cell,and smooth muscle cell;and the expression of calponin・l and osteopontin.The penile shortening,peak ICP and ICP drop rate after alprostadil injection were significantly improved with vacuum therapy after 4-week treatme nt.Compared with BCNC group,VED sign ifica ntly in creased smooth muscle/collagen ratios,decreased collagenⅠ/Ⅲratios,and preserved the ultramicrostructure of the tunica albuginea,endothelial cell,and smooth muscle cell.The data also showed that an imals exposed to VED could partially reverse the expression of calp onin・l and osteop ontin induced by BCNC.In conclusion,vacuum therapy is effective to prevent penile shrinkage and veno-occlusive dysfunction in penile rehabilitation,which may be associated with well-preserved structure and function of the tunica albuginea,endothelial cell,and smooth muscle cell.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study

Objective: Hepatic veno-occlusive disease(HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.Methods: This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.Results: Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen(P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived(both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels.Unexpectedly, we found that hydrothorax was detected in 21(65.63%) patients in the death group and 19(59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio(INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.Conclusion: HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

Hepatic venous outflow obstruction:Three similar syndromes

Our goal is to provide a detailed review of veno- occlusive disease (VOD), Budd-Chiari syndrome (BCS), and congestive hepatopathy (CH), all of which results in hepatic venous outflow obstruction. This is the first article in which all three syndromes have been reviewed, enabling the reader to compare the characteristics of these disorders. The histological findings in VOD, BCS, and CH are almost identical: sinusoidal congestion and cell necrosis mostly in perivenular areas of hepatic acini which eventually leads to bridging fibrosis between adjacent central veins. Tender hepatomegaly with jaundice and ascites is common to all three conditions. However, the clinical presentation depends mostly on the extent and rapidity of the outflow obstruction. Although the etiology and treatment are completely different in VOD, BCS, and CH; the similarities in clinical manifestations and liver histology may suggest a common mechanism of hepatic injury and adaptation in response to increased sinusoidal pressure.

Reversible sinusoidal obstruction syndrome associated with tacrolimus following liver transplantation

Sinusoidal obstruction syndrome(SOS), previously known as hepatic veno-occlusive disease, is a rare disorder in solid organ transplant patients, and is an uncommon complication after liver transplantation. Severe SOS with hepatic failure causes considerable mortality. Tacrolimus has been reported to be an offending agent, which potentially plays a role in the pathophysiological process of SOS. SOS due to tacrolimus has been reported in lung and pancreatic transplantations, but has never been described in a liver transplant recipient. Herein, we present a case of SOS after liver transplantation, which was possibly related to tacrolimus. A 27-year-old man developed typical symptoms of SOS with painful hepatomegaly, ascites and jaundice after liver transplantation, which regressed following withdrawal of tacrolimus. By excluding other possible predisposing factors, we concluded that tacrolimus was the most likely cause of SOS.

Imaging of the chemotherapy-induced hepatic damage:Yellow liver,blue liver,and pseudocirrhosis

The liver is the major drug-metabolizing and drug-detoxifying organ.Many drugs can cause liver damage through various mechanisms;however,the liver response to injury includes a relatively narrow spectrum of alterations that,regardless of the cause,are represented by phlogosis,oxidative stress and necrosis.The combination of these alterations mainly results in three radiological findings:vascular alterations,structural changes and metabolic function reduction.Chemotherapy has changed in recent decades in terms of the drugs,protocols and duration,allowing patients a longer life expectancy.As a consequence,we are currently observing an increase in chemotherapy-associated liver injury patterns once considered unusual.Recognizing this form of damage in an early stage is crucial for reconsidering the therapy regimen and thus avoiding severe complications.In this frontier article,we analyze the role of imaging in detecting some of these pathological patterns,such as pseudocirrhosis,“yellow liver”due to chemotherapy-associated steatosis-steatohepatitis,and“blue liver”,including sinusoidal obstruction syndrome,veno-occlusive disease and peliosis.

Gemtuzumab ozogamicin in the treatment of adult acute myeloid leukemia

Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to a derivative of an antitumor antibiotic, calicheamicin. GO was approved for the treatment of relapsed acute myeloid leukemia (AML) in the United States (US) in 2000. However, GO was withdrawn from the US market in June 2010, because a large-scale clinical trial failed to show additive or synergistic effects with conventional chemotherapy for newly diagnosed AML. GO is currently available only in Japan. However, several large clinical studies have demonstrated beneficial effects of GO when added to chemotherapy for AML in recent years;therefore, reconsideration of GO availability is gaining attention. Therefore, the role and efficacy of GO as monotherapy or in combination therapy for de novo or relapsed AML should be positively investigated.

Severe Hepatic Sinusoidal Obstruction Syndrome during the Induction Chemotherapy of Burkitt’s Lymphoma

The Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive disease (VOD), is a well-known complication of haematopoietic stem cell transplantation, of the treatment of Wilms tumor and rhabdomyosarcoma and maintenance therapy of acute lymphoblastic leukemias. Its occurrence is rare in other cancers of the child. We report the observation of a 7-year-old girl with Burkitt’s lymphoma who developed a severe HSOS during her second induction treatment with dexamethasone, cisplatin, cytosine arabinoside. The evolution was fatal. This observation shows that the diagnosis of HSOS should not be excluded in the absence of the risk factors usually described.

Clinical significance of multislice spiral CT scans in hepatic veins occlusion in Budd-Chiari syndrome

Background Budd-Chiari syndrome with hepatic vein occlusion （HVBCS） can induce severe portal hypertension and liver damage. We retrospectively analyzed hepatic CT features of HVBCS and evaluated the usefulness of triphasic enhancement of CT examinations and CT angiography （CTA） in its diagnosis. Methods Twenty-five cases with HVBCS, confirmed by digital subtraction angiography （DSA）, received a triphasic enhancement CT scan within one week before DSA. The CTA images of the relevant blood vessels were reconstructed with maximum intensity projection, volume rendering and oblique reformat techniques. Results Compared with DSA, the detection rate of transverse CT and CTA images for abnormal hepatic vein were 81.7% （58/71） and 95.8% （68/71） （X^2=7.044, P=-0.008）, for membranous obstruction were 47.4% （9/19） and 84.2% （16/19） respectively （X^2 =5.729, P=-0.017 ）, for segmental obstruction were 88.0% （22/25） and 100% （25/25） respectively （X^2=1.418, P=-0.234）. The detection rates for hepatic vein stenosis were 100% with each method. Diffuse hepatomegaly was found in all 6 cases in acute phase and 3 of 19 cases in chronic phase who had severe obstruction of three hepatic veins without patent intrahepatic collaterals. The other 16 cases in chronic phase had hepatatrophia to different extents related to the obstructed hepatic vein. All in acute phase and 15 in chronic phase presented typical patchy enhancement initially in caudate lobe and perihilar areas and enlarged with time delay. In all cases, parenchyma areas with atrophy, necrosis and congestion demonstrated lower and later enhancement. In all the parts, which had normal enhancement at least one patent outflow hepatic vein, accessory hepatic vein or collateral vessel was detected.Conclusion Dynamic enhancement CT examination by multislice spiral CT not only could improve the diagnosis of HVBCS by CTA technique, but also could noninvasively provide anatomical information and reveal damage to the hepatic parenchyma.