A 13-year-old girl presented for evaluation of pulmonary hypertension after symptoms of dyspnea and exercise intolerance. Full evaluation was negative except for abdominal ultrasonography with splenomegaly and esophageal varices suggestive of portal hypertension. Cardiac and hepatic vein catheterization confirmed portopulmonary hypertension. Liver biopsy demonstrated sinusoidal dilatation, nodularity, and minimal fibrosis, which was interpreted as possible nodular regenerative hyperplasia but not cirrhosis. Radiographic imaging, including computed tomography venography, demonstrated an elongated and severely stenotic extrahepatic portal vein, and portal hypertension was presumed to be secondary to congenital portal vein hypoplasia. She was treated with ambrisentan with initial improvement in symptoms and estimated pulmonary pressure. Whole-exome sequencing revealed a likely pathogenic missense mutation in Delta-like canonical Notch ligand 4 associated with Adams-Oliver syndrome. After 2 years, pulmonary hypertension and right heart failure symptoms worsened, along with liver failure. She then had fulminant liver failure and cardiorespiratory arrest. Resuscitative efforts included extracorporeal membranous oxygenation (ECMO), but because of hypoxic brain injury, care was compassionately withdrawn. Autopsy limited to the thorax and abdomen revealed high-grade pulmonary plexiform arteriopathy, splenomegaly, esophageal varices, and large splenorenal shunt. The liver was small with a nodular surface but not fibrotic. The entire length of the extrahepatic portal vein was severely stenotic, and intrahepatic portal veins were missing or diminutive-findings diagnostic of hepatoportal sclerosis. Noncirrhotic portopulmonary hypertension is rare and should include evaluation of immunologic, infectious, toxic, thrombotic, and genetic etiologies. Unfortunately, there is no known treatment of hepatoportal sclerosis.

Arsenic toxicity is rare in developed countries. It may be difficult to diagnose due to its heterogenous symptom presentation. We present a case of severe hepatic steatosis and cholestatic hepatitis associated with arsenic toxicity in an adult.

Aim: The differential diagnosis of intrinsic nonfibrotic conditions that may lead to portal hypertension include hepatoportal sclerosis (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). In this article, we characterize the clinical features and outcome of these lesions when they manifest as portal hypertension. Methods: Data was collected through retrospective patient medical records. Results: Patients (HPS: 28, NRH: 17, SOS: 11) were identified more frequently in recent years. All groups presented with signs and symptoms of portal hypertension. All patients had complex medical histories. An elevated serum alkaline phosphatase occurred in all groups and an elevated bilirubin with SOS. Imaging of the liver with HPS and NRH suggested cirrhosis, which was not seen with SOS. 11%, 12%, and 9% of patients in the HPS, NRH, and SOS respectively, underwent transjugular intrahepatic portosystemic shunt placement to manage the complications of portal hypertension, while 43%, 24%, and 36% of patients respectively, received a liver transplant. Conclusions: Patients with HPS, NRH, and SOS had complex medical histories, likely contributing to the development of these lesions. They are recognized more frequently now. In contrast to HPS and NRH, SOS occurred in liver transplant recipients, was associated with elevated serum bilirubin, and imaging did not suggest the presence of advanced fibrosis/cirrhosis. Liver transplantation appeared to be a viable treatment for complications related to HPS and NRH. Retransplantation for SOS yielded mixed results. HPS, SOS, and NRH should be considered when evaluating liver specimens from patients with unexplained nonfibrotic portal hypertension. Key message: Intrinsic nonfibrotic causes of portal hypertension appear to be increasing in frequency. The differential diagnosis includes NRH, HPS, and SOS. These conditions are associated with complex diseases and possibly due to treatments. Pathologists need to be aware of this differential diagnosis when presented with liver biopsies performed to assess portal hypertension.

Hepatoportal sclerosis (HPS) is an idiopathic non-cirrhotic portal hypertension (INCPH) characterized by hypersplenism, portal hypertension, and splenomegaly. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Non-cirrhotic portal hypertension is an extremely rare cause of HCC. A 36-year-old woman was referred to our hospital with esophageal varices. All serologic tests for etiology were negative. Serum ceruloplasmin and serum Ig A-M-G were normal. In the follow-up, two liver lesions were identified on a triple-phase computer. The lesions had arterial enhancement but no washout in the venous phase. In the magnetic resonance imaging examination, differentiation in favor of HCC was considered at one of the lessions. Radiofrequency ablation therapy was first applied to a patient who had no signs of metastasis. Within 2 months, the patient underwent a living donor liver transplant. In explant pathology, well-differentiated HCC and HPS were considered the cause of non-cirrhotic portal hypertension. The patient has been followed without relapse for 3 years. The development of HCC in INCPH patients is still debatable. Despite the presence of liver cell atypia and pleomorphism in nodular regenerative hyperplasia liver specimens, a causal link between HCC and INCPH is yet to be established.

We describe a case of hepatoportal sclerosis (HPS) identified in an 81-year-old woman taking a traditional Chinese herbal supplementation, Cordyceps. The patient presented with splenomegaly and weight loss. After an extensive evaluation, liver biopsy confirmed loss of the small portal veins with characteristics of obstruction at the level of the small and large portal veins, suggestive of HPS. After a comprehensive history and exclusion of other etiological factors, patient's HPS was attributed to Cordyceps use. Ultimately, the patient's features of HPS improved with the cessation of Cordyceps.