Jesse M. Civan

From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending.

Modeling the overall survival of patients with advanced‐stage non‐small cell lung cancer using data of routine laboratory tests

Cancer patients undergo routine clinical monitoring with an array of blood tests that may carry long‐term prognostic information. We aimed to develop a new prognostic model predicting survival for patients with advanced non‐small cell lung cancer (NSCLC), based on laboratory tests commonly performed in clinical practice. A cohort of 1,161 stage IIIB or IV NSCLC patients was divided into training (n = 773) and testing (n = 388) cohorts. We analyzed the associations of 32 commonly tested laboratory variables with patient survival in the training cohort. We developed a model based on those significant laboratory variables, together with important clinical variables. The model was then evaluated in the testing cohort. Five variables, including albumin, total protein, alkaline phosphatase, blood urea nitrogen and international normalized ratio, were significantly associated with patient survival after stepwise selection. A model incorporating these variables classified patients into low‐, medium‐ and high‐risk groups with median survival of 16.9, 7.2 and 2.1 months, respectively (p < 0.0001). Compared with low‐risk group, patients in the medium‐ and high‐risk groups had a significantly higher risk of death at 1 year, with hazard ratio (HR) of 1.95 (95% CI 1.62–2.36) and 5.22 (4.30–6.34), respectively. These results were validated in the testing cohort. Overall, we developed a prognostic model relying entirely on readily available variables, with similar predictive power to those which depend on more specialized and expensive molecular assays. Further study is necessary to validate and further refine this model, and compare its performance to models based on more specialized and expensive testing.

Giving rituximab in patients with occult or resolved hepatitis B virus infection: are the current guidelines good enough?

Introduction: Hepatitis B virus (HBV) reactivation after ‘resolved’ infection can occur in the setting of immunosuppression, including iatrogenically induced by anti-CD20 antibodies. The presence of antibodies against the HBV core antigen (anti-HBc) is a marker of risk for this phenomenon. The risk of this occurring in patients with circulating HBV surface antigen (HBsAg) is well characterized, but is less well characterized in patients who are HBsAg negative. Areas covered: This article reviews the literature regarding HBV reactivation in the context of rituximab therapy. We have limited our review to HBsAg-negative patients, and clinical outcomes following HBV reactivation. Expert opinion: We have recommended prophylactic anti-viral therapy for all HBsAg-negative/anti-HBc-positive patients undergoing rituximab therapy in combination with other immunosuppressive therapy.

Prospective evidence of a circulating microRNA signature as a non-invasive marker of hepatocellular carcinoma in HBV patients

The predictive value of circulating microRNAs (miRNAs) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been demonstrated in retrospective studies, but it has rarely been tested in prospective studies. In a cohort of 373 cancer-free HBV patients with a median follow-up of 4.5 years, we measured the expression of 24 retrospectively identified HCC-related miRNAs in baseline serum samples. When we analyzed the prospective associations of miRNA expression with HCC risk using the Cox proportional hazards model, we found that 15 of the 24 miRNAs exhibited a significant association with HCC risk. In particular, 7 miRNAs (miR-122, miR-99a, miR-331, miR-125b, miR-23b, miR-92a, and miR-26a) were associated with an increased risk, and 8 miRNAs (miR-652, miR-23a, miR-27a, miR-34a, miR-145, miR-10a, miR-150, and let-7f) were associated with a decreased risk. Compared to HBV patients with a low miRNA-based risk score, those with a high miRNA-based risk score exhibited a significantly elevated HCC risk in both univariate (hazard ratio [HR] 6.56, 95% confidence interval [CI] 2.74-15.70) and multivariate (HR 3.57, 95% CI 1.34-9.48) analyses. The risk score significantly increased the HCC prediction performance of alpha-fetoprotein (concordance index increased from 0.68 to 0.82, P < 0.0001). In silico analyses indicated that the genes targeted by the 15 miRNAs are mainly enriched in the transforming growth factor-beta signaling pathway. Collectively, these results provide prospective evidence that circulating miRNAs serve as non-invasive markers for risk prediction of HCC in HBV patients.

Pulmonary Capillaritis: A Rare Extra-Intestinal Manifestation of Inflammatory Bowel Disease

Pulmonary Capillaritis: A Rare Extra-Intestinal Manifestation of Inflammatory Bowel Disease

Transarterial chemoembolization for palliation of paraneoplastic hypoglycemia in a patient with advanced hepatocellular carcinoma.

The patient underwent an unremarkable open surgical repair of his AAA with the use of polyester graft. At 6-month, follow-up, he remained free from complications. Thrombus from the aneurysm sac was cultured but proved sterile. Infected AAA is uncommon, comprising fewer than 3% of infrarenal AAAs (1), and can be asymptomatic despite the increased risk of rupture and mortality (2). Gas within the sac wall and periaortic inflammatory tissue are features of mycotic aneurysm. In the present case, the immunosuppressive effect of methotrexate could have increased the risk of mycotic aneurysm, as previously reported (3); however, no organisms were cultured in blood or thrombus. Severe rheumatoid disease can cause aortitis, but no periaortic inflammation was seen in the present case (Fig 1). Spontaneous aortoenteric fistula is less common, and reported only in the presence of infection. When there is communication between the aorta and part of the gastrointestinal tract, ectopic gas adjacent to or within the aorta is the predominant CT finding (4). Degenerative disease of the lumbar intervertebral discs may exhibit gas within the degenerate disc. Perhaps the intervertebral gas diffused into the aneurysm sac; however, we are unaware of any reported cases of spontaneous aneurysm sac gas associated with this condition. In conclusion, the present report suggests that aortic sac gas can be a benign finding, independent of aortic infection or aortoenteric fistula.

Profiling HBV integrations in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In this context, chronic viral hepatitis B (HBV) infection represents the most common etiology of HCC. Notably, although other common causes of HCC including chronic viral hepatitis C and chronic alcoholic liver disease are mediated by progression through cirrhosis, the pathogenesis of HCC in HBV infection does not entirely depend on this mechanism. A major proposed pathway by which HCC may arise from chronic HBV infection is the integration of HBV DNA into the host genome, resulting in oncogene activation, tumor-suppressor gene inactivation, or other predisposition to chromosomal instability (1).

Hepatocellular carcinoma after locoregional therapy: Magnetic resonance imaging findings in falsely negative exams.

AIM To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent. METHODS This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 radiologists, blinded to clinical and pathological data, independently reviewed the pre-transplant MRIs for 7 imaging features. Liver explant histopathology provided the reference standard, with clinically significant tumor defined as viable tumor ≥ 1.0 cm in maximum dimension. Fishers exact test was first performed to identify significant imaging features. RESULTS Inclusion criteria selected for 42 patients with 65 treated lesions. Fourteen of 42 patients (33%) and 16 of 65 treated lesions (25%) had clinically significant viable tumor on explant histology. None of the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC. CONCLUSION After locoregional therapy some treated lesions that do not demonstrate any MRI evidence of HCC will contain viable tumor. As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor. The possibility of occult tumor should be a consideration when contemplating any action which might delay liver transplant.

Palmoplantar keratoderma as a presenting sign of primary biliary cirrhosis

P rimary biliary cirrhosis (PBC) is an autoimmune disease of the liver characterized by the presence of highly specific antimitochondrial antibodies with resulting immune-mediated injury of small intrahepatic bile ducts. Palmoplantar keratodermas (PPKs) are characterized by hyperkeratosis of the skin on the palms and soles. Multiple cases have been reported associating PPK with autoimmune thyroiditis. Herein, we report a patient with acquired PPK who was diagnosed with PBC. Treatment of her PBC led to clearance of her PPK.

Management of Small Hepatocellular Carcinoma

Editor: We read with great interest the article by Dr Kierans and colleagues in the January 2016 issue of Radiology titled “The Diagnostic Performance of Dynamic Contrast-enhanced MR Imaging for Detection of Small Hepatocellular Carcinoma Measuring Up to 2 cm: A Meta-Analysis” (1). The authors, in the introduction section, write regarding United Network for Organ Sharing (UNOS)/ Organ Procurement and Transplantation Network (OPTN) policy regarding allocation for liver transplant priority on the basis of hepatocellular carcinoma (HCC), “... a major update to the criteria from 2011 for the first time assigned increased priority for nodules exhibiting classic imaging features of HCC and measuring at least 1 cm but smaller than 2 cm.” Indeed, the new “OPTN 5” classification rigorously defines the radiologic criteria that must be present for lesions to be considered “definite HCC” and does encompass lesions between 1 and 2 cm if requisite radiologic features are present (1). Only lesions so designated as OPTN class 5 are included in the staging of HCC, at least as pertinent to the determination as to whether the patient qualifies for transplant priority, also known as “HCC Model for End-Stage Liver Disease or MELD exception” (2,3). However, it is important to note that although OPTN class 5 lesions smaller than 2 cm contribute to staging of HCC, a solitary OPTN class 5 lesion smaller than 2 cm in fact remains an insufficient basis on which to grant priority for transplantation. According to current UNOS/OPTN policy, only patients with UNOS and/ or clinical stage 2 HCC qualify, that is, either a solitary OPTN class 5 lesion at least 2 cm in maximal diameter or at least two OPTN class 5 lesions if both are smaller than 2 cm (3). How best to treat patients with well-compensated cirrhosis and a small solitary HCC, resection versus transplantation, remains controversial. However, it is important for radiologists to keep in mind in multidisciplinary tumor board discussions that should a strategy of transplantation be pursued, solitary OPTN class 5 lesions smaller than 2 cm do not qualify for transplantation priority under current policy.