Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: A novel pretransplant protocol.

We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. Nine patients received liver transplant out of 27 who were evaluated (33.3%). The median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease, and 4 had treatment-induced cirrhosis. Pretransplant management included chemotherapy (n = 9) +/- bevacizumab (n = 6) and/or anti-EGFR (n = 6). The median number of pre-LT cycles of chemotherapy was 16 (range 10-40). Liver-directed therapy included Yttrium-90 (n = 5), ablation (n = 4), resection (n = 4), and hepatic artery infusion pump (n = 3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n = 6/8) and 60% (n = 3/5). Recurrence occurred in the lungs (n = 1), liver graft (n = 1), and lungs+para-aortic nodes (n = 1). Patients with pre-LT detectable disease had reduced RFS ( p = 0.04). All patients with recurrence had histologically viable tumors in the liver explant. Patients treated in our protocol (n = 16) demonstrated improved survival versus those who were not candidates (n = 11) regardless of transplant status ( p = 0.01). A protocol defined by aggressive pretransplant liver-directed treatment and transplant for patients with the undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers.

BACKGROUND: This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes. METHODS: The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT's for HCC (2003-2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated. RESULTS: Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9-10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551-0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall's c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1-13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713-0.823) and Metroticket 2.0 (AUC = 0.739, 0.677-0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P < 0.001 using competing risk analysis. CONCLUSIONS: Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

Emerging and Clinically Accepted Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept.

INTRODUCTION: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. METHODS: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. RESULTS: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1-124). The median time from pre-operative testing to surgery was 3 months (IQR: 1-4; range: 0-5), and from surgery to post-operative testing, it was 9 months (IQR: 2-22; range: 0.4-112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6-40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/-). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA-/- (n = 1, 10%), and ctDNA-/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. CONCLUSIONS: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience.

BACKGROUND: Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. METHODS: A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. RESULTS: Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% ( n =504) and 86.6% ( n =493). Five-year RFS and OS were 78.9% ( n =449) and 79.1% ( n =450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9-0.95). Tumour size greater than 3 cm ( P =0.012), increasing tumour number on imaging ( P =0.001) and explant pathology ( P <0.001) was associated with recurrence. Transplant within Milan ( P <0.001) or UCSF criteria ( P <0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence ( P <0.001) and reduced OS ( P =0.008). Chemoembolization was predictive of recurrence in the overall population ( P =0.043) and in those outside-Milan criteria ( P =0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS ( P <0.001) in the total cohort and predict both, RFS ( P =0.007) and OS ( P =0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts ( n =15/58, 25.6%, P =0.009). Donor age was associated with a higher HCC recurrence ( P =0.006). Both total ischaemia time (TIT) greater than 6hours ( P =0.016) and increasing TIT correlated with higher HCC recurrence ( P =0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence ( P =0.039) and reduced survival ( P =0.033). CONCLUSION: This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.

Combined Liver Transplant and Cardiac Surgery: Long-Term Outcomes and Predictors of Success.

OBJECTIVE: We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS). SUMMARY BACKGROUND DATA: Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky. METHODS: Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality. RESULTS: Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates. CONCLUSIONS: This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.

Neoplastic Progression of Barrett's Esophagus Among Organ Transplant Recipients: a Retrospective Cohort Study.

BACKGROUND: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression. METHODS: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted. RESULTS: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients. CONCLUSION: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.

Epstein-Barr virus-associated smooth muscle tumors in immunocompromised patients: Six case reports.

BACKGROUND: Epstein-Barr virus associated smooth muscle tumor (EBV-SMT) is a rare oncological entity. However, there is an increasing incidence of EBV-SMTs, as the frequency of organ transplantation and immunosuppression grows. EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder (PTLD). There is no clear consensus on the treatment of EBV-SMTs. However, surgical resection, chemotherapy, radiation therapy, and immunosuppression reduction have been explored with varying degrees of success. CASE SUMMARY: Our case series includes six cases of EBV-SMTs across different age groups, with different treatment modalities, adding to the limited existing literature on this rare tumor. The median latency time between immunosuppression and disease diagnosis is four years. EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency. CONCLUSION: It is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.

Hepatic Epstein-Barr Virus-Associated Smooth Muscle Tumor in a Heart and Liver Transplant Recipient.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMT) have been described in immunosuppressed states, including in post-transplant patients. Here, we discuss a heart-liver transplant recipient who was found to have multifocal hepatic EBV-SMT. His immunosuppression was initially transitioned from tacrolimus to sirolimus because of the proposed benefits of the mechanistic target of rapamycin inhibitors on EBV-SMT. Unfortunately, he suffered acute rejection of his liver allograft while on sirolimus therapy, which ultimately led to consideration of retransplantation.

Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study.

BACKGROUND: There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD. METHODS: Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality. RESULTS: Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64-1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55-2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68-2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13-1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29-2.30, p = 0.71). CONCLUSIONS: Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy.

Successful orthotopic liver transplantation in a patient with a positive SARS-CoV2 test and acute liver failure secondary to acetaminophen overdose.

SARS-CoV2, first described in December 2019, was declared a pandemic by the World Health Organization in March 2020. Various surgical and medical societies promptly published guidelines, based on expert opinion, on managing patients with COVID-19, with a consensus to postpone elective surgeries and procedures. We describe the case of an orthotopic liver transplantation (OLT) in a young female who presented with acute liver failure secondary to acetaminophen toxicity to manage abdominal pain and in the setting of a positive SARS-CoV2 test. Despite a positive test, she had no respiratory symptoms at time of presentation. The positive test was thought to be residual viral load. The patient had a very favorable outcome, likely related to multiple factors including her young age, lack of respiratory COVID-19 manifestations and plasma exchange peri-operatively. We recommend a full work-up for OLT in COVID-19 patients with uncomplicated disease according to standard of care, with careful interpretation of COVID-19 testing in patients presenting with conditions requiring urgent or emergent surgery as well as repeat testing even a few days after initial testing, as this could alter management.

Safety and Outcomes of Combined Liver Transplantation and Cardiac Surgery in Cirrhosis.

BACKGROUND: Decompensation of liver function after cardiac surgery in patients with cirrhosis has resulted in high morbidity and mortality. A treatment strategy, for which there is a scarcity of data in the literature, encompasses combined liver transplantation and cardiac surgery. METHODS: We performed a retrospective analysis of prospectively collected data on 15 patients who underwent combined liver transplantation and cardiac surgery between 2005 to 2017 at our institution. RESULTS: Between 2005 and 2017, 15 patients with cirrhosis and coronary artery disease or valve disease were identified who underwent combined liver transplantation and cardiac surgery. The cardiac disease was considered severe enough to preclude liver transplantation alone. Likewise, the advanced cirrhosis precluded cardiac surgery alone. Eighty percent of the patients were male and average age was 60 years. Six patients had coronary artery disease, 2 patients had severe aortic stenosis and coronary artery disease, 1 patient had severe mitral regurgitation and coronary artery disease, 2 patients had severe aortic stenosis, 1 patient had mitral valve prolapse, and 3 patients had severe aortic insufficiency. The mean model for end-stage liver disease score was 24. Four subjects were Child-Pugh class B, and 11 were class C. One-year survival was 73.3%. CONCLUSIONS: Combined liver transplant and cardiac surgery is feasible in this selected, otherwise inoperable, patient population with an acceptable early and midterm survival when performed in high volume centers with a cohesive multidisciplinary team.

Work up of fatty liver by primary care physicians, review.

Nonalcoholic fatty liver disease (NAFLD) is an overarching term that refers to abnormal deposition of lipids in the liver and is used to describe the spectrum of disease ranging from hepatic steatosis to nonalcoholic steatohepatitis to cirrhosis. NAFLD is the most common cause of chronic liver disease and the second most common cause of cirrhosis. Although the pathophysiology is not completely understood, there is a strong link between NAFLD and metabolic syndrome. This review focuses on the workup of NAFLD in the primary care setting, from differential diagnoses to assessing fibrosis via predictive models that use commonly used laboratory values, biomarkers, and imaging. The purpose of this review article is to provide a set of screening and diagnostic tools for all primary care physicians in order to better manage patients with NAFLD.

Unusual MRI appearance of a well differentiated hepatocellular carcinoma, mimicking a cavernous hemangioma: A case report.

The typical imaging findings in hepatocellular carcinoma (HCC) are arterial hyperenhancement with washout on portal venous and/or equilibrium phases. Larger HCCs can have atypical imaging findings including fibrous capsule or mosaic appearance. We describe an unusual biopsy proven HCC in a cirrhotic liver with imaging features mimicking cavernous hemangioma which also demonstrated some atypical features such as thick capsule. In addition to knowing the typical imaging findings of HCC, it is important to be familiar with its atypical imaging findings especially in larger lesions.

The Use of Vedolizumab in Patients with Concomitant Cirrhosis and Crohn's Disease.

Vedolizumab is a humanized monoclonal α4ß7 integrin antibody used in patients with Crohn's disease (CD) and ulcerative colitis (UC). Limited data are available on the use of vedolizumab in patients with concurrent cirrhosis and inflammatory bowel disease (IBD). Patients with cirrhosis are unique, as they have a predilection for developing opportunistic infections and malignancies. Additionally, it is not known if vedolizumab alters the natural course of cirrhosis. We report our experience in three patients with concomitant CD and cirrhosis, who were treated with vedolizumab. In our limited cohort, all the three patients tolerated vedolizumab well. None of them experienced significant infectious complications, nor did any have decompensated cirrhosis. Our limited series suggest that vedolizumab is well tolerated in patients with compensated cirrhosis.

Ciliated hepatic foregut cyst: report of three cases and review of imaging features.

Ciliated hepatic foregut cysts (CHFCs) are rare cystic lesions which are most commonly asymptomatic. They can be clinically important as they may, on rare occasions, undergo malignant transformation or cause mass effect if significantly enlarged. Three cases of CHFCs are presented in this article and their imaging features are reviewed.

Steatosis and hepatitis C.

Hepatitis C virus (HCV) infection is a common liver disease worldwide with a high rate of chronicity (75-80%) in infected individuals. The chronic form of HCV leads to steatosis, cirrhosis and hepatocellualr carcinoma. Steatosis is prevalent in HCV patients (55%) due to a combination of viral factors (effect of viral proteins on some of the intracellular pathways) and host factors (overweight, insulin resistance, diabetes mellitus, and alcohol consumption). The response rates to treatment of chronic HCV with pegylated interferon (PEG-IFN) and (in the case of genotype-1 HCV, the most common infecting genotype in the USA) ribavirin (RBV) is low, with a sustained viral response rate ≤ 40%. Adding direct-acting antiviral agents-recently approved by the FDA-to the standard protocol has increased the response rate; however HCV-related end-stage liver disease is still the primary indication for liver transplantation in the USA. The focus of this article is on the interrelation between HCV, steatosis and metabolic syndrome.

Clinical presentation and protocol for management of hepatic sarcoidosis.

The liver is one of the most commonly involved extrapulmonary sites in sarcoidosis. Hepatic sarcoidosis has a broad range of presentations from scattered, asymptomatic noncaseating granulomas with normal liver enzymes, which are very common in patients with known pulmonary sarcoidosis, to portal hypertension and cirrhosis, which are relatively uncommon. Diagnosis is based on a combination of clinical, laboratory and histological manifestations. The authors' protocol for management of patients with suspected sarcoidosis of the liver without focal lesions includes a transjugular liver biopsy with portal pressure measurements to confirm the diagnosis, rule out coexisting liver diseases and to identify select patients with fibrosis or portal hypertension for consideration of immunosuppression. Steroids and azathioprine are the preferred agents and methotrexate is not recommended.

Renal axis deviation in urinary tract abnormalities of children: the role of renal scintigraphy.

BACKGROUND: Urinary tract pathologies are common in children. Previous reports suggested a relationship between some renal pathologies and renal anatomic variations. This study evaluates the effect of different urinary tract abnormalities on scintigraphic renal long axis. METHODS: Children referred to our nuclear medicine department for Tc-99m dimercaptosuccinic acid and/or Tc-99m N,N-ethylenedicysteine renal scintigraphies were entered consecutively. Presence of single, ectopic, or fused kidneys, extrarenal pathologies altering renal long axis, and history of renal surgery or advanced renal disease were used as exclusion criteria. If indicated, patients were assessed for vesicoureteral reflux (VUR). Long renal axis of each kidney was drawn with a line passing through the kidney's upper and lower poles using posterior image. The angle between this axis and patient's longitudinal body axis was defined as "renal angle." After defining age-groups, "age-corrected renal angle" was calculated. RESULTS: A total of 311 cases (622 kidney units) entered the study (183 females, 128 males). Mean age was 41.8 months. Mean "renal angle" was 11.7, 11.9, 14.1, 17.6, 28.5, 16.7, and 19.2 degrees in normal, mild, moderate, and severe VUR, high-grade ureteropelvic junction (UPJ) obstruction, nonobstructive pelvic dilatation, and ureterovesical junction obstruction, respectively (P = 0.000). Applying receiver operating characteristic analysis and using ultrasonography as the gold standard, renal angle deviation of 13.75 degrees led to the sensitivity of 74.6% and specificity of 70.7% to detect pyelocalyceal system dilatation. Using a "renal angle" cutoff value of 18.7 degrees, 85% sensitivity and 85% specificity were achieved for the diagnosis of high-grade UPJ obstruction. Using "age-corrected renal angle," a cutoff value of 3.9 degrees was consistent with 60% sensitivity and 73% specificity for the diagnosis of severe VUR. CONCLUSION: Considerable renal axis deviation is noted in patients with UPJ obstruction and severe VUR in children. Measurement of "renal angle" provides indirect but useful clues to the presence of urinary tract pathologies. Renal scintigraphy is a useful tool for drawing renal axis and measuring "renal angle," potentially making it useful for prediction of urinary tract system abnormalities.