Significance of histopathological features in the diagnosis of Budd-Chiari syndrome on liver biopsies.

Background: Budd-Chiari syndrome (BCS) requires a constellation of clinical, imaging, and histological findings for diagnosis. Liver biopsy serves as a tool for confirming the diagnosis, even though the histological characteristics are not pathognomonic. Aims: To determine which constellation of morphologic findings could aid in establishing a diagnosis of BCS in clinically suspected cases. Materials and Methods: A 5-year retrospective observational study was conducted. The clinical, laboratory, and histological findings of liver biopsies in patients with a clinical diagnosis of BCS were studied. Cases were segregated into two groups on the basis of the number of histological features present. A scoring system was then devised to assess the efficacy of the histological findings in diagnosing BCS. Statistical Analysis Used: The continuous variables were compared using the Mann-Whitney U-test, and categorical variables were compared using the Fisher-exact test. Results: The common histopathological findings were the presence of red blood cells in the space of disse (100%), peri-portal fibrosis (97.1%), sinusoidal dilation (97.1%), portal inflammation (67.6%), centrilobular necrosis (61.8%) and pericellular/sinusoidal fibrosis (61.8%). Comparison between the two groups showed that centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis were significant parameters. No correlation was found between the clinical and laboratory parameters and the two groups. Conclusions: The liver biopsy features in BCS are often nonspecific, and no single feature in isolation is characteristic. A constellation of features (centrilobular necrosis, lobular inflammation, portal inflammation, central vein fibrosis, and pericellular/sinusoidal fibrosis), when present together, indicate the possibility of BCS.

A novel two-stage approach to the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome.

OBJECTIVE: To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. PATIENTS AND METHODS: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. RESULTS: Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. CONCLUSION: While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Multiple hemangiomas (hepatic small vessel neoplasia) in the liver with Budd-Chiari syndrome.

Hepatic small vessel neoplasia (HSVN) is a recently recognized hemangioma of the liver with uncertain malignant potential. Almost all the patients are asymptomatic. Budd-Chiari syndrome (BCS) is a rare disorder characterized by noncardiogenic hepatic venous outflow obstruction. Benign hepatocellular nodules have been acknowledged for a long time in the liver with the chronic BCS. However, there has been no case report of BCS associated with HSVN. The patient was diagnosed with BCS 13 years ago. The imaging test initially displayed multiple hepatic nodules that were suspected of benign hepatocellular nodules. They gradually increased in size and number in the course of the disease. At an autopsy, these nodules were confirmed to be multifocal HSVN. The tumor of the present case could not be proved to have GNAQ and GNQ14 mutations. We describe the case focusing on the chronological imaging changes and discuss on the relationship between BCS and HSVN.

Single-center study: evaluation of sonography in Budd-Chiari syndrome.

PURPOSE: Budd-Chiari syndrome (BCS) is a rare disease characterized by hepatic venous outflow tract obstruction. The study aimed to evaluate the diagnostic utility of ultrasound in confirming the diagnosis of BCS and to provide an overview of the clinical picture. MATERIALS AND METHOD: In this retrospective single-center study, patients with an initial diagnosis of BCS were included. The files were analyzed concerning the ultrasound images and compared to computed tomography (CT) and magnetic resonance imaging (MRI). Main clinical signs of BCS were collected. RESULTS: Data of 25 patients were analyzed. Doppler sonography showed the highest sensitivity (78.9%) with the highest specificity 97.4 (%) in confirming the correct diagnosis of BCS. Main imaging signs were obstruction in the hepatic veins (68.0%, 17/25 thrombotic), collaterals (91.7%, 11/12 intrahepatic), inhomogeneous liver parenchyma (7/21), and a hypertrophied lobus caudatus (18/21) (p < 0.01). All imaging signs could be detected with sonography. Hypertrophied lobus caudatus was seen exclusively in BCS. Furthermore, portal hypertension (9/25), liver cirrhosis (9/25), and ascites (19/25) can be diagnosed as non-specific signs of BCS (p < 0.01).The main clinical findings were elevated γ-GT levels in the laboratory (92.0%, 23/25, p < 0.01) and esophageal varices in endoscopy (12/25 p < 0.01). An association with myeloproliferative neoplasia (MPN) was frequently seen (10/25) (p < 0.01). CONCLUSION: The present study demonstrates that sonography is an appropriate tool for the diagnosis of BCS and should be used as the first imaging procedure.

Sintilimab plus sorafenib: a novel regimen for hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most common malignant tumors in China and is also a major cause of cancer deaths worldwide. Recent advances in immunotherapy have identified new treatments in which immunotherapy can be combined with antiangiogenic therapy. We report a case of hepatocellular carcinoma with a tumor thrombus at the inferior vena cava-right atrium junction and multiple lung metastases after a multiple-course treatment. Treatment with sintilimab in combination with sorafenib led to a partial remission and immune-related hepatitis.

Lay abstract Hepatocellular carcinoma is often found at intermediate or advanced stages and thus often has a poor outcome. This is due to a high chance of return and spread of the cancer. Combining immunotherapy and targeted therapy can improve the anticancer effects of treatment. Here we describe a patient with hepatocellular carcinoma who developed widespread cancer after multiple-course treatment. Sintilimab combined with sorafenib shrunk the tumor. This shows this regimen as a promising treatment strategy for hepatocellular carcinoma.

Small hepatic veins Budd-Chiari syndrome and paroxysmal nocturnal hemoglobinuria - The association of two rare entities: a case report.

Small hepatic veins Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction limited to the small intrahepatic veins, with normal appearance of the large hepatic veins at imaging. In this case only a liver biopsy can demonstrate the presence of a small vessels outflow block. Paroxysmal nocturnal haemoglobinuria (PNH) is one of the most severe acquired thrombophilic state and represents one of the main aetiological factors of Budd-Chiari syndrome. In patient affected by PNH with liver impairment and/or ascites, Budd-Chiari syndrome must be always taken into consideration and, if necessary, a liver biopsy performed to exclude the small hepatic veins involvement. We report a case of small hepatic veins Budd-Chiari syndrome secondary to paroxysmal nocturnal haemoglobinuria.

Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

A Comparison of Splenic Pathologic Change and Immune Function in HBV-Related Portal Hypertension and Chinese Budd-Chiari Syndrome Patients with Hypersplenism.

The difference of splenic pathologic alterations and immune function changes in portal hypertension (PHT) with different etiology is unclear. We aimed to investigate the differences between the hypersplenic patients with hepatitis B virus (HBV)-related PHT and Budd-Chiari syndrome (B-CS). A total of 93 patients with hypersplenism due to Chinese primary B-CS (B-CS group), 105 patients with hypersplenism due to HBV-related cirrhosis (HBV/PHT group), and 31 healthy people (control group) were included in this study retrospectively. The peripheral bloods and paraffin sections of the spleen from part of patients were analyzed by flow cytometry and immunohistochemistry. Hypersplenism and PHT were more serious in HBV/PHT group than in B-CS group. In the peripheral blood, the percentages of regulatory T cell (15.1% vs. 8.1% vs. 2.2%, p = 0.0021) and myeloid-derived suppressive cells (2.8% vs. 0.8% vs. 0.9%, p = 0.009) were higher, but CD4+ T and CD8+ T cells were lower in HBV/PHT group compared with B-CS and control groups. In spleen, the percentages of CD4+ T and CD8+ T cells were lower, but CD68+ macrophages were higher in HBV/PHT group than in B-CS group. Moreover, CD86, inducible nitric oxide synthase, Toll-like receptor 4, and tumor necrosis factor-α expression in the spleen, as well as the plasma lipopolysaccharide (LPS) level (677.7 vs. 311.1 vs. 222.1 ng/mL, p = 0.0022), were significantly higher in HBV/PHT group than in B-CS and control groups. The HBV/PHT group showed more severe immunosuppression and immune dysfunction and more substantial hypersplenism and splenic phagocytosis than B-CS group.

Budd-Chiari Syndrome and hepatic regenerative nodules: Magnetic resonance findings with emphasis of hepatobiliary phase.

Budd-Chiari syndrome (BCS) is a disorder with numerous causes that is a result of hepatic outflow obstruction, in the absence of right heart failure or constrictive pericarditis. Acute Budd-Chiari syndrome is uncommon and clinically characterized by ascites, hepatomegaly, and hepatic insufficiency. In the majority of cases, patients present with chronic BCS, showing a dysmorphic liver disease with variable fibrosis deposition. In chronic Budd-Chiari syndrome, hepatocellular carcinoma (HCC) and benign regenerative nodules (called large regenerative nodules or FNH-like lesions) have been described in the literature. Very few studies have reported magnetic resonance imaging (MRI) findings about these nodules, using hepatobiliary contrast medium. The aim of our review is to describe the magnetic resonance imaging findings of hepatic regenerative nodules in BCS, with emphasis on the hepatobiliary phase, and to compare the imaging features of benign nodules with those of HCC.

Immunohistochemical and Ultrastructural Features of Hepatocellular Cytoplasmic Globules in Venous Outflow Impairment.

OBJECTIVES: To examine the immunohistochemical and ultrastructural features of hepatocellular cytoplasmic globules in venous outflow impairment (VOI). METHODS: Sixty-four liver core biopsies were screened. Patients with α-1 antitrypsin (AAT) deficiency were excluded. All biopsies were stained with H&E, Masson trichrome, periodic acid-Schiff with diastase digestion (PAS-D), phosphotungstic acid hematoxylin (PTAH), complement protein 4d (C4d) immunostain, and AAT immunostain. Electron microscopy was also performed. RESULTS: Hepatocellular globules were identified in 8% of in-house cases. Causes of VOI included heart failure and Budd-Chiari syndrome. The hepatocellular cytoplasmic globules showed size variability, random distribution, and positivity for PAS-D, PTAH, and AAT. C4d was inconsistently positive. Electron microscopy showed that the globules were lysosome-bound inclusions containing microfibrillar material and fibrinogen. CONCLUSIONS: PAS-D-positive hepatocellular globules occur in VOI. They cross-react with AAT but have different appearance, localization, and ultrastructural composition from globules in AAT deficiency.

Residual cancerous lesion and vein tumour thrombus identified intraoperatively using a fluorescence navigation system in liver surgery.

AIM: The main aims of this study are to investigate the clinical application value of using indocyanine green fluorescence imaging for ensuring complete resection of tumour tissue during hepatectomy and to evaluate the diagnostic efficacy of near-infrared (NIR) fluorescence imaging system using indocyanine green in hepatectomy. METHODS: After undergoing liver resection at the Affiliated Hospital of Southwest Medical University from July 2017 to May 2018, 35 eligible patients were included in this study. The liver surface and resection margin were intraoperatively assessed by intraoperative ultrasonography and NIR fluorescence imaging, after intravenous administration of indocyanine green (0.5 mg/kg) 72-96 h prior to surgery. The intraoperative observations were compared with the pathological findings in the liver. RESULTS: In the 35 patients, a total of 53 lesions were found, of which 42 were malignant lesions. The analysis results showed that the sensitivity and accuracy of detection using NIR fluorescence imaging were significantly higher than with intraoperative ultrasonography (P < 0.05). However, there was no difference between contrast-enhanced helical computed tomography and NIR fluorescence imaging in finding lesions (P > 0.05). In addition, 11 new suspicious lesions were detected only by NIR fluorescence imaging in the liver surface and resection margin during surgery, four of which were hepatocellular carcinoma. We also detected four vein tumour thrombi using the NIR fluorescence navigation system. CONCLUSIONS: The NIR fluorescence navigation system enables the identification of small tumours, residual cancer tissues in resection margin and venous tumour embolies in real time and enhances the accuracy and integrity of liver resection.

Homocysteine Serum Levels as Prognostic Marker of Hepatocellular Carcinoma with Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of endstage hepatocellular carcinoma (HCC). The aim of our study was to evaluate the role of Homocysteine (Hcy) in HCC patient with PVT. Hcy is a sulphur amino-acid involved in two pathways, trans-sulphuration and remethylation, that involve vitamins B6, B12 and folates. METHODS: We recruited 54 patients with HCC and PVT, 60 patients with HCC and without PVT and 60 control subjects. We measured serum levels of Hcy, folate, vitamins B6 and B12. RESULTS: The comparison between HCC patients with PVT versus HCC without PVT was shown that mean values of Hcy were 6.4 nmol/L (p<0.0073) higher, LDL cholesterol were 4.8 mg/dl (p<0.0079) lower, vitamin B6 were 4.6 nmol/L(p=0.0544) lower, vitamins B 12 were 22.1 pg/ml (p=0.0001) lower. CONCLUSION: High serum levels of Hcy are an established thrombotic risk factor in the general population. We found significantly higher levels of Hcy in HCC patients with PVT versus both HCC patients without PVT and controls.

Low specificity of washout to diagnose hepatocellular carcinoma in nodules showing arterial hyperenhancement in patients with Budd-Chiari syndrome.

BACKGROUND & AIMS: It remains unclear whether the classic imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be applied to chronic vascular liver diseases, such as Budd-Chiari syndrome (BCS). Herein, we aimed to evaluate the diagnostic value of washout for the discrimination between benign and malignant lesions in patients with BCS. METHODS: This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal lesions on MRI from 2000 to 2016. MRI images were reviewed by 2 radiologists blinded to the nature of the lesions. Patient and lesion characteristics were recorded, with a focus on washout on portal venous and/or delayed phases. Lesions were compared using Chi-square, Fisher's, Student's t or Mann-Whitney U tests. RESULTS: A total of 49 patients (mean age 35 ±â€¯12 years; 34 women [69%] and 15 men [31%]) with 241 benign lesions and 12 HCC lesions were analyzed. Patients with HCC were significantly older (mean age 44 ±â€¯16 vs. 33 ±â€¯9 years, p = 0.005), with higher alpha-fetoprotein (AFP) levels (median 16 vs. 3 ng/ml, p = 0.007). Washout was depicted in 9/12 (75%) HCC, and 69/241 (29%) benign lesions (p <0.001). A total of 52/143 (36%) lesions ≥1 cm with arterial hyperenhancement showed washout (9 HCC and 43 benign lesions). In this subgroup, the specificity of washout for the diagnosis of HCC was 67%. Adding T1-w hypointensity raised the specificity to 100%. A serum AFP >15 ng/ml was associated with 95% specificity. CONCLUSION: Washout was observed in close to one-third of benign lesions, leading to an unacceptably low specificity for the diagnosis of HCC. The non-invasive diagnostic criteria proposed for cirrhotic patients cannot be extrapolated to patients with BCS. LAY SUMMARY: Washout on MRI is depicted in a significant proportion of benign nodules in patients with Budd-Chiari syndrome (BCS), limiting its value for the differentiation between benign and malignant lesions. Criteria proposed for the non-invasive diagnosis of hepatocellular carcinoma in patients with cirrhosis cannot be extrapolated to patients with BCS. Additional imaging findings and patient characteristics, including alpha-fetoprotein serum level, can help determine the probability of a nodule being HCC in patients with BCS.

Intravenous Lymphatic Cyst in Inferior Vena Cava-A Rare Cause of Budd-Chiari Syndrome.

A case with an extremely rare intravenous cystic lesion in the suprahepatic inferior vena cava was reported, which originated from the lymphatic system and had induced Budd-Chiari syndrome. To the best of our knowledge, this is the first report of a benign cystic lesion originating from the wall of a suprahepatic inferior vena cava which results in Budd-Chiari syndrome.