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Phrathep DD, Anthony S, Healey KD, Khan H, Herman M. Portal Hypertension Due to Hepatoportal Sclerosis in an HIV-Positive Patient Secondary to Didanosine Use. Cureus 2023; 15:e36364. [PMID: 37082489 PMCID: PMC10112855 DOI: 10.7759/cureus.36364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2023] [Indexed: 03/20/2023] Open
Abstract
Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an HIV-infected patient with portal hypertension due to hepatoportal sclerosis who presented with hematemesis at the emergency department (ED). CT angiography of the abdomen and pelvis with and without contrast revealed a diminutive portal vein with corresponding massive lower esophageal varices and superior mesenteric vein to the right gonadal vein varices. Esophagogastroduodenoscopy (EGD) revealed grade II varices were found in the lower third of the esophagus, for which the patient's symptoms improved with emergency endoscopic band ligation, octreotide and didanosine discontinuation. Our case demonstrates a rare complication that can occur with continued didanosine use in an HIV-positive patient. We highlight the need for a standard diagnostic upper gastrointestinal endoscopy to screen for portal hypertension and high-risk esophageal varices in patients with long-term didanosine use as seen in our patient.
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Araújo C, Nunes VS, Santos G, Freitas LARD, Schinoni MI, Paraná R. HISTOPATHOLOGICAL, CLINICAL AND EPIDEMIOLOGICAL FEATURES OF HEPATOPORTAL SCLEROSIS IN A REFERRAL CENTER FOR LIVER DISEASE IN NORTHEASTERN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:276-280. [PMID: 34705959 DOI: 10.1590/s0004-2803.202100000-48] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 02/09/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.
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Affiliation(s)
- Caio Araújo
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil
| | - Vinícius Santos Nunes
- Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, BA, Brasil
| | - Genario Santos
- Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, BA, Brasil
| | - Luiz Antônio Rodrigues de Freitas
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil.,Instituto Gonçalo Moniz - Fundação Oswaldo Cruz, Departamento de Patologia, Salvador, BA, Brasil
| | | | - Raymundo Paraná
- Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil
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Abstract
PURPOSE OF REVIEW Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. RECENT FINDINGS Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. SUMMARY Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.
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Kleiner DE. Histopathological challenges in suspected drug-induced liver injury. Liver Int 2018; 38:198-209. [PMID: 28865179 DOI: 10.1111/liv.13584] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/25/2017] [Indexed: 12/13/2022]
Abstract
When a patient with suspected drug-induced liver injury (DILI) undergoes liver biopsy, the pathologist is confronted with two major challenges. The first and most important is to establish the pattern(s) of injury which are present. Patterns of injury represent stereotypical responses of an organ to injury and relate to specific aetiologies of liver damage. The pattern of injury and the histological details of that injury can then be analysed with respect to the patient's intercurrent diseases and medication history. The specific expertise of the pathologist can be used to weigh the prospect of DILI against the likelihood of other explanations of injury. The second challenge is to characterize specific types of injury and the severity of injury, both of which may have importance for clinical decision-making and prognosis. The pathologist's report should convey both an accurate description of the pathology as well its interpretation.
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Affiliation(s)
- David E Kleiner
- Post-Mortem Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA
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6
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Sherman KE, Peters MG, Thomas D. Human immunodeficiency virus and liver disease: A comprehensive update. Hepatol Commun 2017; 1:987-1001. [PMID: 30838978 PMCID: PMC5721407 DOI: 10.1002/hep4.1112] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/29/2017] [Accepted: 09/19/2017] [Indexed: 12/16/2022] Open
Abstract
Among persons living with human immunodeficiency virus (HIV) infection, liver disease remains a major cause of morbidity and mortality. While the etiologies are varied and often overlapping in the individual patient, the underlying mechanisms, including oxidative stress, direct activation of stellate cells, HIV interaction with hepatocytes, and bacterial translocation with systemic immune activation, seem to be unifying characteristics. Early and fully suppressive HIV antiretroviral therapy is a mainstay of management either before or concurrent with treatment of etiologic cofactors, including hepatitis C virus, hepatitis B virus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Significant barriers to care that still exist include liver disease recognition, appropriate linkage to care, ongoing substance abuse, and psychiatric comorbidities in the HIV-infected population. Emerging issues in these patients include acute and chronic hepatitis E, underreported hepatitis D, and a rising incidence of hepatocellular carcinoma. (Hepatology Communications 2017;1:987-1001).
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7
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Xue Y, Farris AB, Quigley B, Krasinskas A. The Impact of New Technologic and Molecular Advances in the Daily Practice of Gastrointestinal and Hepatobiliary Pathology. Arch Pathol Lab Med 2017; 141:517-527. [PMID: 28157407 DOI: 10.5858/arpa.2016-0261-sa] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The practice of anatomic pathology, and of gastrointestinal pathology in particular, has been dramatically transformed in the past decade. In addition to the multitude of diseases, syndromes, and clinical entities encountered in daily clinical practice, the increasing integration of new technologic and molecular advances into the field of gastroenterology is occurring at a fast pace. Application of these advances has challenged pathologists to correlate newer methodologies with existing morphologic criteria, which in many instances still provide the gold standard for diagnosis. This review describes the impact of new technologic and molecular advances on the daily practice of gastrointestinal and hepatobiliary pathology. We discuss new drugs that can affect the gastrointestinal tract and liver, new endoluminal techniques, new molecular tests that are often performed reflexively, new imaging techniques for evaluating hepatocellular carcinoma, and modified approaches to the gross and histologic assessment of tissues that have been exposed to neoadjuvant therapies.
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Affiliation(s)
| | | | | | - Alyssa Krasinskas
- From the Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
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Progression of Hepatic Adenoma to Carcinoma in the Setting of Hepatoportal Sclerosis in HIV Patient: Case Report and Review of the Literature. Case Reports Hepatol 2016; 2016:1732069. [PMID: 27812395 PMCID: PMC5080467 DOI: 10.1155/2016/1732069] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 09/28/2016] [Indexed: 11/17/2022] Open
Abstract
We report a case of hepatic adenoma progression to carcinoma in the setting of hepatoportal sclerosis in an HIV+ patient and provide a review of the scarce literature regarding hepatoportal sclerosis in HIV patients. We describe the clinical presentation, diagnostic workup, and management. This is the first case report in the literature of progression of hepatic adenoma to carcinoma in hepatoportal sclerosis in an HIV patient. This case also highlights the broad differential diagnosis that should always be included in the study of any liver disease in this patient population, including the performance of invasive and aggressive tests to arrive at the final diagnosis.
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Lee H, Rehman AU, Fiel MI. Idiopathic Noncirrhotic Portal Hypertension: An Appraisal. J Pathol Transl Med 2015; 50:17-25. [PMID: 26563701 PMCID: PMC4734966 DOI: 10.4132/jptm.2015.09.23] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 09/23/2015] [Indexed: 02/07/2023] Open
Abstract
Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.
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Affiliation(s)
- Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - Aseeb Ur Rehman
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA
| | - M Isabel Fiel
- Department of Pathology, The Mount Sinai Medical Center, New York, NY, USA
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Abstract
There are an estimated 40 million HIV infected individuals worldwide, with chronic liver disease being the 2nd leading cause of mortality in this population. Elevated liver functions are commonly noted in HIV patients and the etiologies are varied. Viral hepatitis B and C, fatty liver and drug induced liver injury are more common. Treatment options for viral hepatitis C are rapidly evolving and are promising, but treatments are limited for the other conditions and is primarily supportive. Opportunistic infections of the liver are now uncommon. Irrespective of etiology, management requires referral to specialized centers and with due diligence mortality can be reduced.
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Sood A, Castrejón M, Saab S. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review. World J Hepatol 2014; 6:55-63. [PMID: 24653794 PMCID: PMC3953810 DOI: 10.4254/wjh.v6.i1.55] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia (NRH) in patients with human immunodeficiency virus (HIV).
METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: “nodular regenerative hyperplasia”, “human immunodeficiency virus”, “noncirrhotic portal hypertension”, “idiopathic portal hypertension”, “cryptogenic liver disease”, “highly active antiretroviral therapy” and “didanosine”. The bibliographies of these studies were subsequently searched for any additional relevant publications.
RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH.
CONCLUSION: The appropriate management of HIV-infected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.
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12
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Sherman KE, Thomas D, Chung RT. Human immunodeficiency virus and liver disease forum 2012. Hepatology 2014; 59:307-17. [PMID: 23904401 PMCID: PMC3849330 DOI: 10.1002/hep.26638] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 06/24/2013] [Accepted: 07/13/2013] [Indexed: 02/06/2023]
Abstract
In the United States, more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis, leading to cirrhosis and liver-related mortality. Etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection, including increased bacterial translocation, immune activation, and presence of soluble proteins, that modulate the hepatic cytokine environment. New treatments for hepatitis C virus (HCV) using direct-acting agents appear viable, though issues related to intrinsic toxicities and drug-drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in recent years, may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status.
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Affiliation(s)
- Kenneth E. Sherman
- Division of Digestive Diseases; University of Cincinnati College of Medicine; Cincinnati OH
| | - David Thomas
- Division of Infectious Diseases; Johns Hopkins Medical Institute; Baltimore MD
| | - Raymond T. Chung
- Harvard Medical School, Massachusetts General Hospital; Boston MA
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13
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Abstract
Drug-induced hepatotoxicity is underrecognized but increasingly identified as causing acute and chronic liver disease. Several prescription drugs, over-the-counter medications, dietary and/or supplementary agents, and herbal products are hepatotoxic. Drug-induced liver injury mimics other primary acute and chronic liver diseases and it should be considered in patients with hepatobiliary disease. Certain drugs result in specific histopathologic patterns of liver injury, which may help in sorting out the responsible drug. The diagnosis of drug-induced hepatotoxicity is challenging. It involves excluding other possible causes, careful medication history, the latent period between drug exposure and symptom onset and/or abnormal liver tests, and histopathologic findings.
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Affiliation(s)
- Xuchen Zhang
- Department of Pathology, VA Connecticut Health System and Yale University School of Medicine, 310 Cedar Street, LH 108, New Haven, CT 06516, USA.
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14
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Aggarwal S, Fiel MI, Schiano TD. Obliterative portal venopathy: a clinical and histopathological review. Dig Dis Sci 2013; 58:2767-76. [PMID: 23812828 DOI: 10.1007/s10620-013-2736-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 05/29/2013] [Indexed: 12/12/2022]
Abstract
Non-cirrhotic portal hypertension (NCPH) is characterized by the elevation of the portal pressure in the absence of cirrhosis. Obliterative portal venopathy (OPV) as a cause of NCPH is being increasingly diagnosed, especially after recent reports of its occurrence in patients with HIV using didanosine. Patients usually present with episodes of variceal hemorrhage and other features of portal hypertension including jaundice, ascites, encephalopathy and hepatopulmonary syndrome. Hepatic synthetic function is typically well preserved and the laboratory evaluation in OPV patients typically reveals only mild nonspecific hematological abnormalities chiefly related to hypersplenism. Its diagnosis remains a challenge and patients are often mistakenly diagnosed as having cirrhosis. Despite the increasing recognition of OPV, its etiology and pathogenesis are still unclear. A number of etiologies have been proposed including genetic predisposition, recurrent bacterial infections, HIV infection and highly active antiretroviral therapy, an altered immune response, hypercoagulability, and exposure to chemicals and certain medications. Histopathological evaluation remains critical in excluding cirrhosis and other causes of portal hypertension, and is the only way of definitively establishing the diagnosis of OPV. Clinicians should have a high index of suspicion for OPV in patients who present with variceal bleeding and splenomegaly and who do not have other features of cirrhosis. The purpose of this review is to summarize the known etiologies for OPV and its associated clinical aspects and correlations, and to also provide ample histophotomicrographs of OPV to aid in the diagnosis. It will also help raise awareness of this entity amongst pathologists and clinicians alike.
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Affiliation(s)
- Sourabh Aggarwal
- School of Medicine, Western Michigan University, Kalamazoo, MI, USA
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Agrawal M, Rahmani R, Nakkala K, Fiel MI, Schiano T. Hepatoportal sclerosis (obliterative portal venopathy) and nodular regenerative hyperplasia in a patient with myasthenia gravis: A case report and review of the published work. Hepatol Res 2013; 43:999-1003. [PMID: 23675894 DOI: 10.1111/hepr.12045] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Revised: 11/29/2012] [Accepted: 12/13/2012] [Indexed: 12/14/2022]
Abstract
Nodular regenerative hyperplasia (NRH) and hepatoportal sclerosis, also known as obliterative portal venopathy (OPV), are two causes of non-cirrhotic portal hypertension (NCPH). NCPH is an increasingly recognized entity that can be seen in association with collagen vascular diseases and with the use of medications such as azathioprine and didanosine, but oftentimes the etiology remains unidentified. We herein report a case of NCPH occurring due to OPV and NRH in a 64-year-old woman with myasthenia gravis (MG), status post-thymectomy. Portal hypertension was diagnosed incidentally on computed tomography in the absence of predisposing factors. Extensive work-up to determine the etiology of any underlying liver disease was unrevealing. NRH and OPV were identified on liver biopsy. Subsequently, the patient had variceal bleeding that necessitated transjugular intrahepatic portosystemic shunt placement. A few similar cases of NCPH occurring in the setting of MG have been previously reported, suggesting that the immunological mechanisms involved in the pathogenesis of myasthenia may also have contributed to the development of NCPH.
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Affiliation(s)
- Manasi Agrawal
- Department of Internal Medicine, Division of Gastroenterology, Maimonides Medical Center, Brooklyn
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Parikh ND, Martel-Laferriere V, Kushner T, Childs K, Vachon ML, Dronamraju D, Taylor C, Fiel MI, Schiano T, Nelson M, Agarwal K, Dieterich DT. Clinical factors that predict noncirrhotic portal hypertension in HIV-infected patients: a proposed diagnostic algorithm. J Infect Dis 2013; 209:734-8. [PMID: 23911709 DOI: 10.1093/infdis/jit412] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.
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Affiliation(s)
- Neil D Parikh
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
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Tuyama AC, Krakauer M, Alzaabi M, Fiel MI, Legnani P, Schiano TD. Mercaptopurine-induced hepatoportal sclerosis in a patient with Crohn's disease. J Crohns Colitis 2013; 7:590-3. [PMID: 22841133 DOI: 10.1016/j.crohns.2012.07.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2012] [Revised: 07/06/2012] [Accepted: 07/06/2012] [Indexed: 02/08/2023]
Abstract
Thiopurines play a pivotal role in the management of inflammatory bowel disease. Azathioprine and mercaptopurine have been associated with a number of liver abnormalities, including hepatitis, veno-occlusive disease, nodular regenerative hyperplasia, and peliosis hepatitis. Patients treated with azathioprine and mercaptopurine have their liver chemistry tests routinely checked due to this potential for hepatotoxicity. Hepatoportal sclerosis is a cause of non-cirrhotic portal hypertension that is increasingly being recognized; its etiopathogenesis is not well defined. We present the first case report of mercaptopurine-induced hepatoportal sclerosis leading to non-cirrhotic portal hypertension in a patient with Crohn's disease. He had been treated with mercaptopurine for five years, and his liver chemistry tests were always within normal limits. This case underscores the potential serious liver adverse events that may arise silently and go undetected during treatment with mercaptopurine, and should alert clinicians as to the potential need to discontinue mercaptopurine in this setting.
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Affiliation(s)
- Ana C Tuyama
- Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, United States
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18
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Fierer DS, Dieterich DT, Fiel MI, Branch AD, Marks KM, Fusco DN, Hsu R, Smith DM, Fierer J. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis 2012; 56:1038-43. [PMID: 23264364 DOI: 10.1093/cid/cis1206] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND We and others have shown that primary hepatitis C (HCV) infection in men infected with human immunodeficiency virus (HIV) causes early-onset liver fibrosis; however, little is known about the long-term natural history of the liver disease in these HIV-infected men. METHODS We followed a cohort of HIV-infected men with primary HCV infection in New York City. RESULTS Four men who were not cured after their primary HCV infection developed decompensated cirrhosis within 17 months to 6 years after primary HCV infection. Three died within 8 years of primary HCV infection, and 1 survived after liver transplant done 2 years after primary HCV infection. Three of the 4 men had AIDS at the time of primary HCV infection, and the most rapid progression occurred in the 2 men with the lowest CD4 counts at the time of HCV infection. Liver histopathology was most consistent with HCV-induced damage even though some had exposures to other potential hepatotoxins. CONCLUSIONS Primary HCV infection resulted in decompensated cirrhosis and death within 2-8 years in 4 HIV-infected men. The rapid onset of fibrosis due to primary HCV infection in HIV-infected men cannot therefore be considered benign. The rate of continued progression to liver failure may be proportional to the degree of underlying immunocompromise caused by HIV infection. More research is needed to better define the mechanisms behind accelerated liver damage.
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Affiliation(s)
- Daniel S Fierer
- Divisions of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.
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Jackson BD, Doyle JS, Hoy JF, Roberts SK, Colman J, Hellard ME, Sasadeusz JJ, Iser DM. Non-cirrhotic portal hypertension in HIV mono-infected patients. J Gastroenterol Hepatol 2012; 27:1512-9. [PMID: 22497527 DOI: 10.1111/j.1440-1746.2012.07148.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Unexplained liver injury including fibrosis and portal hypertension has rarely been reported among patients with HIV in the absence of co-infection with hepatitis B (HBV) or hepatitis C (HCV). We describe a series of HIV mono-infected patients with evidence of non-cirrhotic portal hypertension. METHODS HIV-infected patients with evidence of portal hypertension who were anti-HBV and anti-HCV negative and HBV and HCV RNA polymerase chain reaction (PCR) negative were identified from patients managed by the Victorian statewide HIV referral service located at The Alfred Hospital, Melbourne. Portal hypertension was defined as either radiological or endoscopic evidence of varices, portal vein flow obstruction, or elevated hepatic venous pressure gradient (HPVG). RESULTS Five patients were found to have portal hypertension. These patients were male, aged 41 to 65 years, with known duration of HIV infection between 11 to 25 years. All had been treated with antiretroviral therapy, including didanosine. Tests for metabolic, autoimmune, and hereditary causes of liver disease failed to establish an etiology for the liver injury. All had radiological or endoscopic findings of varices, and four patients had radiological features of portal vein obstruction or flow reversal. Only one patient underwent HPVG measurement, which was elevated. Non-invasive fibrosis assessment revealed increased liver stiffness in three (out of four) patients, and no cirrhotic features were found on those who underwent liver biopsy. CONCLUSIONS To our knowledge, this is the largest published series of non-cirrhotic portal hypertension in HIV mono-infected patients in Australia. Further research is needed to understand what relationship, if any, HIV or its treatments might have on liver injury over time.
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Affiliation(s)
- Belinda D Jackson
- Department of Gastroenterology, The Alfred Hospital Infectious Diseases Unit, The Alfred Hospital, Australia
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Taylor LE, Swan T, Mayer KH. HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms. Clin Infect Dis 2012; 55 Suppl 1:S33-42. [PMID: 22715212 PMCID: PMC3491862 DOI: 10.1093/cid/cis367] [Citation(s) in RCA: 120] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2012] [Accepted: 03/23/2012] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection has become a major threat to the survival of human immunodeficiency virus (HIV)-infected persons in areas where antiretroviral therapy is available. In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused. Novel therapies may be particularly beneficial for this population, yet studies lag behind those for HCV monoinfection. Increasingly, incident HCV among HIV-infected men who have sex with men is associated with sexual risk behavior further research should be performed to refine understanding of the causal mechanism of this association. The phenomenon of aggressive hepatic fibrogenesis when HIV infection precedes HCV acquisition requires longer-term observation to ensure optimal timing of HCV therapy. Medical management in coinfection will be improved by enhancing HCV detection, with annual serologic testing, screening with HCV RNA to detect acute infection, and HIV testing of HCV-infected individuals; by addressing HCV earlier in coinfected persons; and by universal consideration for HCV therapy. HCV drug trials in individuals coinfected with HIV should be expedited. HIV/HCV coinfection remains a growing and evolving epidemic; new developments in therapeutics and improved care models offer promise.
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Affiliation(s)
- Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI 02906, USA.
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Saison J, Cotte L, Chidiac C, Ferry T. Fatal cumulative toxicities of HAART in a stable, AIDS-free, HIV-infected patient. BMJ Case Rep 2012; 2012:bcr.10.2011.4905. [PMID: 22605589 DOI: 10.1136/bcr.10.2011.4905] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The authors describe the case of fatal cumulative toxicities in a 58-year-old AIDS-free, HIV-infected patient, who successively developed under highly active antiretroviral therapy (HAART): severe lipodystrophy, complicated osteoporosis, complicated non-cirrhotic portal hypertension of the liver (with ascites, portal thrombosis, oesophageal varices and protein-losing enteropathy) due to nodular regenerative hyperplasia. These cumulative HAART-related toxicities led to death, despite symptomatic treatment and the switch of antiretrovirals (especially didanosine) putatively involved in the process in these drug-mediated diseases. As morbidity and mortality in HIV infection continue to improve, it appears important to recognise such rare HAART-associated toxicities. This case illustrates the absolute necessity of investigating the long-term side effects of HAART in HIV infection, particularly in patients treated with first generation molecules. The switch strategy (switching old molecules to newer ones) is crucial in case of severe suspected toxicity and has to be discussed in asymptomatic patients largely exposed to first generation molecules, in order to prevent long-term toxicity.
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Affiliation(s)
- Julien Saison
- Hospices Civils de Lyon, Service de Maladies Infectieuses et Tropicales, Lyon, France
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Sherman KE, Thomas DL, Chung RT. Human immunodeficiency virus and liver disease forum 2010: conference proceedings. Hepatology 2011; 54:2245-53. [PMID: 21898501 PMCID: PMC3795389 DOI: 10.1002/hep.24651] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Liver disease continues to represent a critical mediator of morbidity and mortality in those with human immunodeficiency virus (HIV) infection. The frequent presence and overlap of concomitant injurious processes, including hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of immunosuppression lead to rapid fibrotic progression and early development of end-stage liver disease. This conference summary describes the proceedings of a state-of-the-art gathering of international experts designed to highlight the status of current research in epidemiology, natural history, pathogenesis, and treatment of HIV and liver disease.
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Affiliation(s)
- Kenneth E. Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH
| | - David L. Thomas
- Division of Infectious Diseases, Johns Hopkins University Medical Center, Baltimore, MD
| | - Raymond T. Chung
- Harvard Medical School and Massachusetts General Hospital, Boston, MA
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