The HBx protein from hepatitis B virus coordinates a redox-active Fe-S cluster.

The viral protein HBx is the key regulatory factor of the hepatitis B virus (HBV) and the main etiology for HBV-associated liver diseases, such as cirrhosis and hepatocellular carcinoma. Historically, HBx has defied biochemical and structural characterization, deterring efforts to understand its molecular mechanisms. Here we show that soluble HBx fused to solubility tags copurifies with either a [2Fe-2S] or a [4Fe-4S] cluster, a feature that is shared among five HBV genotypes. We show that the O2-stable [2Fe-2S] cluster form converts to an O2-sensitive [4Fe-4S] state when reacted with chemical reductants, a transformation that is best described by a reductive coupling mechanism reminiscent of Fe-S cluster scaffold proteins. In addition, the Fe-S cluster conversions are partially reversible in successive reduction-oxidation cycles, with cluster loss mainly occurring during (re)oxidation. The considerably negative reduction potential of the [4Fe-4S]2+/1+ couple (-520 mV) suggests that electron transfer may not be likely in the cell. Collectively, our findings identify HBx as an Fe-S protein with striking similarities to Fe-S scaffold proteins both in cluster type and reductive transformation. An Fe-S cluster in HBx offers new insights into its previously unknown molecular properties and sets the stage for deciphering the roles of HBx-associated iron (mis)regulation and reactive oxygen species in the context of liver tumorigenesis.

MRI of Peliosis Hepatis: A Case Series Presentation With a 2022 Systematic Literature Update.

BACKGROUND: Peliosis hepatis (PH) is a rare benign condition, characterized by hepatic sinusoidal dilatation and blood-filled cystic cavities, often found incidentally, with still challenging diagnosis by imaging due to polymorphic appearance. PURPOSE: Based on a retrospective analysis of our series (12 patients) and systematic literature review (1990-2022), to organize data about PH and identify features to improve characterization. STUDY TYPE: Retrospective case series and systematic review. POPULATION: Twelve patients (mean age 48 years, 55% female) with pathology-proven PH and 49 patients (mean age 52 years, 67% female) identified in 33 studies from the literature (1990-2022). FIELD STRENGTH/SEQUENCE: 1,5-T; T1-weighted (T1W), T2-weighted (T2W), diffusion-weighted (DW), contrast-enhanced (CE) T1W imaging. ASSESSMENT: We compared our series and literature data in terms of demographic (gender/age/ethnicity), clinical characteristics (symptoms/physical examination/liver test), associated conditions (malignancies/infectious/hematologic/genetic or chronic disorders/drugs or toxic exposure) percentage. On magnetic resonance imaging lesion numbers/shape/mean maximum diameter/location/mass effect/signal intensity were compared. PH pathological type/proposed imaging diagnosis/patient follow-up were also considered. STATISTICAL TESTS: Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports/Series quality assessment. Intraclass correlation and Cohen's kappa coefficients for levels of inter/intrareader agreement in our experience. RESULTS: Patients were mainly asymptomatic (92% vs. 70% in our study and literature) with associated conditions (83% vs. 80%). Lesions showed homogeneous T1W-hypointensity (58% vs. 65%) and T2W-hyperintensity (58% vs. 66%). Heterogeneous nonspecific (25% vs. 51%), centrifugal (34% vs. 8%), or rim-like centripetal (25% vs. 23%) patterns of enhancement were most frequent, with hypointensity on the hepatobiliary phase (HBP), without restricted diffusivity. Good inter- and intrareader agreement was observed in our experience. Concerning JBI Checklist, 19 out of 31 case reports met at least 7 out of 8 criteria, whereas 2 case series fulfilled 5 and 6 out of 10 items respectively. DATA CONCLUSION: A homogeneous, not well-demarcated T1W-hypointense and T2W-hyperintense mass, with heterogeneous nonspecific or rim-like centripetal or centrifugal pattern of enhancement, and hypointensity on HBP, may be helpful for PH diagnosis. Among associated conditions, malignancies and drug exposures were the most frequent. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Living-donor liver transplantation for liver hemorrhaging due to peliosis hepatis in X-linked myotubular myopathy: Two cases and a literature review.

X-linked myotubular myopathy (MTM) (OMIM 310400) is a severe neuromuscular disorder caused by mutations in the myotubularin (MTM1) gene. Liver hemorrhaging due to peliosis hepatis (PH) is a fatal complication. We herein report 2 successful cases of living-donor liver transplantation (LDLT) for MTM patients due to liver hemorrhaging caused by PH and review previous reports. A boy who was 9 years and 4 months old initially underwent left lateral segmentectomy due to massive hepatic and intraperitoneal hemorrhaging. As bleeding from the remnant liver continued after hepatectomy, this patient emergently underwent LDLT using a left lateral segment graft from his father. Another boy who was 1 year and 7 months old underwent transcatheter arterial embolization due to hepatic hemorrhaging and was referred to our hospital for LDLT using a left lateral segment graft from his father. The pathological findings in both cases showed sinusoidal dilatation with degenerative changes in reticular fiber and hematoma in the explanted liver, which were consistent with PH associated with MTM. LT should be considered as a treatment option for patients with episodes of hepatic hemorrhaging due to MTM in order to protect against fatal bleeding.

[Magnetic resonance imaging and diffusion weighted imaging features of focal peliosis hepatis].

Objective: To investigate the MRI and diffusion weighted imaging (DWI) features of focal peliosis hepatis. Methods: The clinical data and MRI of 19 cases with focal peliosis hepatis confirmed by pathology from January 2012 to March 2018 in Zhongshan Hospital of Fudan University were retrospectively analyzed. The number, location, size, shape, signal intensity of plain scan of lesions, enhancement pattern of lesions, vessels within lesions, and perfusion disorders of hepatic parenchyma were analyzed. The apparent diffusion coefficient (ADC) values of the lesions and adjacent hepatic parenchyma were measured, then the differences between them were explored statistically. All 24 lesions were categorized into group A with tumor-related chemotherapy and group B without tumor-related chemotherapy. The differences of MR features between the two groups were explored statistically. Results: In all 24 lesions, 22 lesions were located in the right lobe, 2 lesions in the left lobe. The median size was 7.5-72.0 (24.4±17.2) mm.On T(1)WI,21 lesions showed slightly hypointensity, 1 lesion showed slightly hyperintensity and 2 lesions were isointensity; all 24 lesions showed slightly hyperintensity on T(2)WI, and isointensity or slightly hyperintensity on DWI. The mean ADC value was (1.511±0.415)×10(-3) mm(2)/s in the lesions and (1.769±0.690)×10(-3) mm(2)/s in the adjacent hepatic parenchyma, which showed no difference between the two groups (P>0.05). On dynamic MR images, 20 lesions showed gradually filling enhancement, 4 lesions showed markedly and persistent enhancement. Punctiform or filiform vessels were found in 9 lesions. Adjacent hepatic perfusion disorders showed in 8 lesions. The median lesion size was 7.5-38.5(17.6±9.8) mm in the tumor-related-chemotherapy group and 9.0-72.0(33.8±21.2) mm in the no chemotherapy group.There was significant difference between the two groups (P<0.05). Conclusions: The MRI performance of focal peliosis hepatis had a certain characteristic. MRI combined with diffusion weighted imaging could help to make diagnoses.

Spontaneous hepatic rupture in a bodybuilder: a case report and review of the literature.

This article is the first description of a spontaneous hepatic rupture in a young bodybuilder with a history of clenbuterol and ephedrine alkaloid use. The patient presented with a sudden mid-epigastric pain and vomiting. Hemoglobin levels decreased a few hours later and a computed tomography scan was performed which revealed a rupture of the right liver capsule and hemoperitoneum. Two attempts at transarterial embolization did not control the bleeding and a right hemihepatectomy was performed. The pathological report identified a hepatic adenoma, a capsular tear and diffuse peliosis hepatis. The patient was discharged in a good condition after eleven days. Spontaneous hepatic ruptures are rare and life-threatening and are usually described in association with tumors, connective tissue diseases and gestosis. This article is a review of the available literature with regard to this condition, with a focus on its relation to peliosis hepatis and banned substance used by body image fanatics. The present case highlights the challenging diagnosis of this potentially fatal liver complication in a healthy appearing male, the risk associated with the online trade of performance enhancing drugs and its relation with peliosis hepatis.

Danazol-induced peliosis hepatis accompanied by disseminated intravascular coagulation in a patient with myelodysplastic syndrome transformed from aplastic anemia.

Peliosis hepatis (PH) is a condition involving benign tumors pathologically characterized by multiple blood-filled cavities, mostly affecting the liver and spleen. Androgenic-steroids are widely used in patients with bone marrow failure syndromes (e.g.: aplastic anemia) and these patients are at increased risk of developing PH. Although patients with PH are generally asymptomatic, PH can progress to liver failure and even fatal spontaneous intraabdominal hemorrhage. Therefore, early diagnosis is critical in order to prevent life-threatening complications of PH. We herein report a patient with PH which had been treated with danazol, who presented with liver dysfunction and multiple hepatic lesions on imaging studies at the time of diagnosis. Although the patient presented with disseminated intravascular coagulation (DIC), a bone marrow biopsy revealed no evidence of leukemic transformation. The patient was diagnosed as having danazol-induced PH, and these abnormalities spontaneously resolved after the discontinuation of danazol. PH is one of the most important complications of long-term administration of androgenic-steroids. Although the mechanisms remain unclear, the multiple blood-filled cavities characteristic of PH may be responsible for the development of DIC. Therefore, monitoring of coagulation markers might also be a key strategy for early diagnosis of PH.

Spontaneous hepatic rupture during pregnancy in a patient with peliosis hepatis.

Spontaneous hepatic rupture (SHR) during pregnancy is a rare but well known complication and it usually occurs alongside eclampsia or HELLP syndrome. SHR in uncomplicated pregnancy is extremely rare and can be associated to different undiagnosed pathological conditions. We report the case of a nulliparous woman, 27 weeks pregnant, with a peliosis hepatis, previously unknown, who was admitted to our unit due to SHR and massive hemoperitoneum. The conception was obtained by embryo transfer after multiple attempts of hormone-supported cycles using estrogens and progesterone. After emergency laparotomy the patient was submitted to deliver of the dead foetus and damage control of the hepatic bleeding source. At relaparotomy a right posterior sectionectomy (segments VI and VII) and segmentectomy of segment V were performed. The patient was discharged in good physical conditions after 18 days from admission. If hepatic rupture is suspected in a pregnant patient a collaborative multidisciplinary approach is mandatory. The cornerstones of medical and surgical management are highlighted. At the best of our knowledge this is the first case of SHR in a pregnant woman with peliosis hepatis. A possible correlation of an increased risk for SHR in a pregnant patient who was submitted to several attempts for embryo transfer is discussed. The relevant scientific literature of the possible causative role of the estrogen therapy in inducing politic liver damage is also reviewed.

Peliosis hepatis due to disseminated tuberculosis in a patient with AIDS.

Peliosis hepatis is a rare histopathological entity of unknown etiology. We present a case of peliosis hepatis in a 44-year-old man with disseminated tuberculosis and acquired immunodeficiency syndrome. The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. Diagnosis of tuberculosis was confirmed by auramine stain, rRNA amplification and culture of Mycobacterium tuberculosis from synovial fluid of the elbow joint. The patient responded favourably to tuberculostatic treatment with four drugs and the early initiation of highly active antiretroviral therapy. Histopathological evidence of peliosis hepatis, without an obvious cause, makes it necessary to rule out tuberculosis, especially in the context of immunodeficiency diseases and immigrants from endemic areas.

Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4-5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

[Primary hepatic angiosarcoma: a clinical and pathological analysis].

OBJECTIVE: To investigate the clinicopathological characteristics, differential diagnosis, and prognosis of primary hepatic angiosarcoma, and to review the literature. METHODS: Twenty cases of primary hepatic angiosarcoma were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD34, CD31, FVIIIRAg, CK, GPC-3, Hepatocyte,vimentin, PTEN, desmin, and CD117. RESULTS: The age of the patients ranged from 7 to 86 years. Eleven cases were male, and 9 were female. All cases showed no specific clinical manifestations and imaging results. Macroscopically, the tumors showed diffuse multi-nodular or single nodular patterns with hemorrhage. Microscopically, there were various patterns such as cavernous vascular space and epithelioid hemangioendothelioma-like appearances; however, specific pathological diagnostic features of angiosarcoma still existed in all cases. All of the cases expressed at least one of the three immunohistochemical markers: CD31, CD34 and/or FVIIIRag. Ten cases had PTEN low expression. Ki-67 proliferative index was more than 10% in all cases. None of cases expressed desmin, CD117, GPC-3 or Hepatocyte. CONCLUSIONS: Primary hepatic angiosarcoma is a rare malignant tumor. Detailed morphological observation and using various vascular endothelial immunohistochemical markers can help to establish the diagnosis accurately.

Hepatic Angiosarcoma with Peliosis Hepatis.

A 59-year-old woman presented to our hospital with liver dysfunction. Imaging revealed multiple lesions in the liver. The patient was diagnosed with peliosis hepatis using percutaneous and laparoscopic biopsies. However, her condition worsened with the appearance of new, obvious mass-forming lesions. Therefore, she underwent a second percutaneous biopsy of these lesions and was diagnosed with hepatic angiosarcoma. Her condition progressed rapidly, and she died two weeks after the diagnosis. Diagnosis of hepatic angiosarcoma in the early stages is difficult. It should be noted that hepatic angiosarcoma may be associated with the development of peliosis hepatis.

Peliosis hepatis presenting as liver rupture in a vulnerable adult: a case report.

Liver rupture is a serious, life-threatening event that is commonly due to blunt abdominal trauma, which should be suspected in a patient who is unconscious or unable to communicate. We report an autopsy case of a 28-year-old woman with severe developmental delay who presented to the emergency department with hemoperitoneum due to massive liver rupture and subsequently died without a diagnosis. An autopsy performed by the hospital pathology department confirmed hemoperitoneum due to hepatic rupture. The case was then referred to the medical examiner to exclude a traumatic etiology. After review of the clinical data, radiological images, and gross and microscopic pathological features, a diagnosis of peliosis hepatis was established. This rare entity has been reported previously as a cause of spontaneous, nontraumatic liver rupture and is reported here to demonstrate its characteristic features and potential to present as fatal hepatic rupture in circumstances in which occult injury must be excluded.

[A 38-year-old patient with gastroenteritis and unusual liver lesions]. / 38-jährige Patientin mit Gastroenteritis und ungewöhnlichen Leberherden.

A 38-year-old female presented with symptoms of gastroenteritis including fatigue and epigastric pain. An abdominal ultrasound indicated on the basis of raised liver values showed multiple liver lesions. However, additional imaging using contrast-enhanced ultrasound (CEUS), computer tomography (CT) as well as a magnetic resonance tomography (MR) failed to clarify the diagnosis. A fine needle biopsy revealed the histological diagnosis of peliosis hepatis. After discontinuing oral contraceptive medication, follow-up showed a steady state with clinical well being for at least 24 months.Peliosis hepatis is a rare hepatic disorder involving "bloody cysts" in the liver. Aetiology and pathogenesis remain unclear, but medication or toxins as possible triggering factors are discussed. Different clinical courses have been reported, including total asymptomatic state, unspecific fatigue, epigastric pain, as well as fulminant cases with liver rupture and bleeding complications.

Haemophagocytic lymphohistiocytosis associated with bartonella peliosis hepatis following kidney transplantation in a patient with HIV.

Bacillary peliosis hepatis is a well recognised manifestation of disseminated Bartonella henselae infection that can occur in immunocompromised individuals. Haemophagocytic lymphohistiocytosis is an immune-mediated condition with features that can overlap with a severe primary infection such as disseminated Bartonella spp infection. We report a case of bacillary peliosis hepatis and secondary haemophagocytic lymphohistiocytosis due to disseminated Bartonella spp infection in a kidney-transplant recipient with well controlled HIV. The patient reported 2 weeks of fever and abdominal pain and was found to have hepatomegaly. He recalled exposure to a sick dog but reported no cat exposures. Laboratory evaluation was notable for pancytopenia and cholestatic injury. The patient met more than five of eight clinical criteria for haemophagocytic lymphohistiocytosis. Pathology review of a bone marrow core biopsy identified haemophagocytosis. A transjugular liver biopsy was done, and histopathology review identified peliosis hepatis. Warthin-Starry staining of the bone marrow showed pleiomorphic coccobacillary organisms. The B henselae IgG titre was 1:512, and Bartonella-specific DNA targets were detected by peripheral blood PCR. Treatment with doxycycline, increased prednisone, and pausing the mycophenolate component of his transplant immunosuppression regimen resulted in an excellent clinical response. Secondary haemophagocytic lymphohistiocytosis can be difficult to distinguish from severe systemic infection. A high index of suspicion can support the diagnosis of systemic Bartonella spp infection in those who present with haemophagocytic lymphohistiocytosis, especially in patients with hepatomegaly, immunosuppression, and germane animal exposures.

Adhesins of Bartonella spp.

Adhesion to host cells represents the first step in the infection process and one of the decisive features in the pathogenicity of Bartonella spp. B. henselae and B. quintana are considered to be the most important human pathogenic species, responsible for cat scratch disease, bacillary angiomatosis, trench fever and other diseases. The ability to cause vasculoproliferative disorders and intraerythrocytic bacteraemia are unique features of the genus Bartonella. Consequently, the interaction with endothelial cells and erythrocytes is a focus in Bartonella research. The genus harbours a variety of trimeric autotransporter adhesins (TAAs) such as the Bartonella adhesin A (BadA) of B. henselae and the variably expressed outer-membrane proteins (Vomps) of B. quintana, which display remarkable variations in length and modular construction. These adhesins mediate many of the biologically-important properties of Bartonella spp. such as adherence to endothelial cells and extracellular matrix proteins and induction of angiogenic gene programming. There is also significant evidence that the laterally acquired Trw-conjugation systems of Bartonella spp. mediate host-specific adherence to erythrocytes. Other potential adhesins are the filamentous haemagglutinins and several outer membrane proteins. The exact molecular functions of these adhesins and their interplay with other pathogenicity factors (e.g., the VirB/D4 type 4 secretion system) need to be analysed in detail to understand how these pathogens adapt to their mammalian hosts.