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Correspondence: Address correspondence to: Raouf E. Nakhleh, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224.
The aim of this study was to review a large series of cases with hepatoportal sclerosis (HPS) as a pathologically recognizable entity in liver tissue specimens and describe the associated clinical and radiographic manifestations, along with the outcomes of this entity.
Methods
Data were collected through a retrospective chart review.
Results
Twenty-eight patients were identified that had pathologically defined HPS. All patients had a significant past medical history and signs and symptoms of portal hypertension. The most consistent laboratory finding was an elevated alkaline phosphatase. Radiographically, 9 patients were mistakenly identified as having advanced fibrosis/cirrhosis. The initial histologic diagnosis was made on biopsy in 20 patients and after transplant in 8 patients. The severity of symptoms was variable and required transplantation in 11 patients, 3 were treated with transjugular intrahepatic portosystemic shunt, and the remaining patients were treated symptomatically.
Conclusion
HPS is associated with past medical history that may be causal in nature. Signs and symptoms may be severe enough to require liver transplantation. A significant proportion of patients are radiographically misdiagnosed as cirrhosis. In this small series, overall outcomes for transplanted patients are acceptable.
Porto-sinusoidal vascular disorder (PSVD) is the term that has recently been adopted to describe a broad range of clinical entities that encompass non-cirrhotic portal hypertension.
Many of these lesions are confusing and often referred to by multiple names (often based on clinical findings and not pathologic findings). One of these lesions is hepatoportal sclerosis (HPS). This is a condition that is localized to the pre-sinusoidal intrahepatic portion of the portal venous circulation and is characterized clinically by an increased portal pressure with patent portal and hepatic veins, without evidence of cirrhosis.
The primary hepatic lesions seen in HPS are varying degrees of fibrosis and sclerosis of the portal vein (PV) branches seen on microscopic examination (Figure).
The aim of this study was to review a large series of cases with HPS as a pathologically recognizable entity on liver tissue specimens and describe the associated clinical and radiographic manifestations, along with the outcomes of this entity.
FigurePortal tract with a portal vein (yellow arrow) that is sclerosed (trichrome stain 100X).
We conducted a retrospective search for the diagnosis of HPS in our surgical pathology files at Mayo Clinic, Florida, from 2000 to 2020. Institutional review board approval was obtained for this minimal risk study. Cases were confirmed by an experienced liver pathologist. The presence of sclerotic PV branches was the main criterion for inclusion in this study. Patients with other liver disease were excluded from the study. A chart review was conducted for the clinical presentation, laboratory and radiographic studies, associated pathology findings, treatment, and outcome.
Results
There were 28 patients in our series (Table 1). Only 4 patients were referred with a diagnosis of HPS. The remaining patients had symptoms and signs of portal hypertension (PHT). Six patients had hepatic encephalopathy (HE) and 2 were diagnosed with hepatopulmonary syndrome. Past medical history was relevant in most cases: 7 (25%) patients had a history of malignancy, receiving various chemotherapeutic agents (Table 2); 14 (50%) patients had an extrahepatic autoimmune disease; 5 patients had congenital vascular anomalies, and 1 patient was infected with human immunodeficiency virus. Twelve of 15 patients who underwent hepatic venography had an elevated hepatic venous pressure gradient greater than 5 mmHg. Computerized tomography and magnetic resonance imaging studies were available in 25 patients. Findings of cirrhosis and advanced fibrosis were described in 8 and 1 case, respectfully. Caudate lobe hypertrophy was noted in 2 cases. One patient had a prior right lobe resection with left lobe hyperplasia. One patient demonstrated a nonocclusive thrombus in the main PV with occlusion of the right PV. Another patient demonstrated attenuation and delayed filling of the PV branches. In 1 patient, there was absence of the PV with splenic and superior mesenteric veins draining into a hepatic venous confluence along the medial border of the liver.
Table 1Clinical and Pathologic Findings in 28 Patients With Hepatoportal Sclerosis
Histologic diagnosis was made on biopsy in 20 patients. The initial diagnosis was made on the explanted livers in the remaining 8 cases (4 with prior biopsies). Treatment and outcome are listed in Table 1.
Three patients underwent transjugular intrahepatic portosystemic shunt (TIPS) placement to manage complications of PHT. Another patient had a TIPS placed prior to a bowel resection for Crohn’s disease given the presence of significant PHT. Eleven patients proceeded to liver transplantation (LT)—the indications for transplant were HE refractory to medical therapy (5 patients, 2 of whom were post-TIPS), heptopulmonary syndrome (2 patients), progressive spastic paresis post-TIPS and progressive liver dysfunction (1 patient each). Other indications for LT included malnutrition (2) and pulmonary hypertension (2). Some patients had more than 1 indication for LT. One patient underwent simultaneous liver and kidney transplant for refractory HE and end-stage renal disease, respectively. The mean biological model for end-stage liver disease score at the time of LT was 15 (range, 7–38); 1 patient was on warfarin at the time of LT. Four patients had been awarded model for end-stage liver disease exception scores given their presentation to expedite transplantation. Four of the LT recipients died postoperatively, one at the time of surgery, the other 3 surviving for a mean of 5 years (range, 4–6 years); 1 patient required retransplantation 6 days after the first LT for hepatic artery thrombosis. The remaining 7 patients were alive at a median of 3 years post-LT (range, 2 months–17 years). Two of the 3 patients who had a TIPS were alive while the third patient was lost to follow-up.
Discussion
PSVD is the latest term used to encompass various histologic changes in the liver in the presence of PHT, including HPS.
In this report, we sought to describe a cohort of patients with HPS who were clearly defined by the histologic finding of sclerotic PV tributaries with associated PHT. The lesion may be identified with hematoxylin and eosin stain, but trichrome and elastin stains may also be helpful in defining the portal structures. Sclerosed PV can be seen in other conditions including cirrhotic livers.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
The determination of PHT without cirrhosis and other conditions should trigger a pathologic assessment for HPS, nodular regenerative hyperplasia (NRH), and sinusoidal obstructive syndrome (SOS).
Drug toxicity from cancer chemotherapy or from immunosuppressive agents to hepatic endothelial cells are likely mechanisms for these injuries. Several of our patients also had congenital vascular anomalies causing hemodynamic mechanical injury. We believe HPS may develop by multiple mechanisms of endothelial injury leads to occlusive thrombosis, or fibrointimal proliferation resulting in PHT. The latter mechanism seems more likely as we found no histologic evidence of organizing thrombosis in any of our cases.
Other conditions that result in PSVD have reported associations with autoimmune disorders and malignancies.
Most notably, NRH and SOS may present with complications of non-cirrhotic portal hypertension, like HPS. SOS occurs after drug or toxin exposure, classically in blood and marrow transplant recipients.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
SOS is defined by sinusoidal endothelial injury with subsequent obstruction of the terminal sinusoids at or near the central veins. Given the similarities between HPS, SOS, and NRH, it may be that they are different manifestations of the same endothelial and/or vascular injury, or an injury that is occurring in different location(s) within the hepatic circulation.
In patients with complications of PHT refractory to medical therapy, TIPS or even LT can be considered in appropriately selected patients.
In our series, as is typical for HPS, very few patients were recognized based solely on their clinical presentation or imaging findings. Only 1 of our patients had classic radiographic features of attenuation and delayed filling of the PV branches.
Interestingly, 9 patients were radiographically determined to have advanced fibrosis which was not confirmed by histology.
HPS is in the spectrum of PSVD. The diagnosis requires recognizing characteristic histologic findings in patients who have PHT in the absence of cirrhosis. Most of our study cohort had a condition that could have contributed to the development of HPS and required treatment to manage the complications of PHT. A significant proportion required LT because of complications refractory to medical therapy, including HE and hepatopulmonary syndrome. Outcomes after LT were acceptable.
Authors' Contributions:
Nazia Khatoon; Andrew P. Keaveny; Gian P. Carames; Raouf E. Nakhleh: Data collection. Nazia Khatoon; Andrew P. Keaveny; Gian P. Carames; Murli Krishna; Jason Lewis; Raouf E. Nakhleh: Data analysis. Nazia Khatoon; Andrew P. Keaveny; Murli Krishna; Jason Lewis; Raouf E. Nakhleh: Manuscript preparation and editing.
References
de Franchis R.
Bosch J.
Garcia-Tsao G.
et al.
Baveno VII—renewing consensus in portal hypertension.
Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.
Conflicts of Interest: The authors disclose no conflicts.
Funding: The authors report no funding.
Ethical Statement: The corresponding author, on behalf of all authors, jointly and severally, certifies that their institution has approved the protocol for any investigation involving humans or animals and that all experimentation was conducted in conformity with ethical and humane principles of research.
Data Transparency Statement: Data will not be made available for other researchers.
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