Dermatologic findings are common in liver disease, and may represent the very earliest or most prominent signs of an underlying disorder. While most practitioners recognize jaundice as a sign of hepatobiliary disease, there are numerous cutaneous signs which can point to concomitant liver dysfunction. Additional signs of liver disease may include findings like disseminated superficial actinic porokeratosis or Terry's nails in cirrhosis, or porphyria cutanea tarda in hepatitis C. It is important for general practitioners and dermatologists alike to be able to recognize and describe such lesions, as identification of cutaneous manifestations of liver disease can lead to earlier diagnosis and treatment initiation for patients. In this article, we present the spectrum of typical associated cutaneous findings of hepatitis B, hepatitis C, and cirrhosis.

Chronic liver disease is often accompanied by cutaneous findings indicative of underlying pathology. However, in addition to the many widely-known and recognizable dermatologic manifestations, there exists a multitude of subtle, lesser-known findings which warrant increased attention. Recognition of these dermatologic findings is invaluable, as they contribute to the diagnostic picture and can aid in prioritization of the differential diagnosis. It is vital for providers across specialties to be able to recognize and describe such lesions in order to help reduce diagnostic delay and hasten time to treatment. In this article, we present the associated cutaneous findings for common liver diseases including autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, and metabolic dysfunction-associated steatotic liver disease.

Liver cancer (LC) is frequently preceded by cirrhosis and poses a significant public health challenge in the United States (US). Recent decades have seen notable shifts in the epidemiological patterns of LC, yet national data guiding the optimal allocation of resources and preventive efforts remain limited. This study aims to investigate the current trends, risk factors, and outcomes of LC in the US. This study utilized the Global Burden of Disease (GBD) dataset to collect data on the annual incident cases, deaths, Disability-Adjusted Life Years (DALYs), age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized DALY rates of primary LC and its etiologies and risk factors, between 1990 and 2019. Percentage changes in incident cases, DALYs, and deaths and the estimated annual percentage change (EAPC) in ASIR and deaths rates of LC were calculated to conduct temporal analysis. Linear regression was applied for the calculation of EAPCs. Correlations of EAPC with socio-demographic index (SDI) were separately evaluated by Pearson correlation analyses. We observed a marked increase in the ASIR of LC, increasing from 2.22 (95

Background:Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases' endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey. Methods:A voluntary survey via Survey Monkey with nine objective-type questions was sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected, and a chi square test was used to compare the two groups. A P value ≤ 0.05 was considered statistically significant. Results:A total of 64 PCPs (29.1%) and 15 cardiologists (20%) completed the survey. Overall, 12.6% did not prescribe statins for primary prevention of atherosclerotic cardiovascular disease in compensated cirrhotic patients. While all cardiologists prescribed statins for secondary prevention, over 50% preferred lower-intensity options. Conversely, 14.1% of PCPs avoided statin prescriptions for secondary prevention. Cardiologists were significantly more inclined to prescribe statins, especially for cirrhosis due to metabolic dysfunction-associated steatotic liver disease compared to PCPs (73.3% vs 45.3%, P = 0.05). Conclusions:Despite increasing evidence favoring use of statins in cirrhosis for improving portal hemodynamics and decreasing ascites, hepatic encephalopathy, the incidence of hepatocellular carcinoma, and mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap.

Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor often used in clinical conjunction with calcineurin inhibitors (CNIs) or mycophenolate mofetil to prevent solid organ transplant rejection. While nephrotoxicity is a well-known side effect of CNIs, renal injury because of mTOR inhibitors is exceedingly rare and limited to case reports, primarily in the setting of renal transplant and post-hematopoietic stem cell transplant. This case demonstrates a rare occurrence of sirolimus-induced thrombotic microangiopathy after orthotopic liver transplant.

Introduction: Relative adrenal insufficiency (RAI) is associated with increased mortality in critically ill patients. It can be seen in patients with cirrhosis, especially with decompensated disease, often described as “hepato-adrenal syndrome”. We conducted a systematic review and meta-analysis to assess the true incidence of RAI among decompensated cirrhotics and its effects on outcomes. Methods: We conducted a comprehensive search of Ovid Cochrane, Ovid Embase, Ovid Medline, Scopus, and Web of Science (inception to July 2021) to identify studies reporting on relative adrenal insufficiency in decompensated cirrhosis. RAI was diagnosed as an increase in serum total cortisol < 9 mcg/dl after standard dose-synacthen stimulation test. The primary outcome was incidence of RAI; secondary outcomes were risk ratio of ascites, hepato-renal syndrome, ICU admission and in-hospital mortality. Standardized mean difference and meta-analysis of proportions was done for outcomes. Results: Out of 249 studies, 8 were included in final analysis based on inclusion criteria. 710 patients, with 502 males (70.7%), mean age 56.53 ± 3.81 years were analyzed. Pooled incidence of RAI in decompensated cirrhosis was 38% (8 studies; CI: 29.5 - 47.6; I2= 82.19%). Patients with RAI had higher MELD score with mean difference 0.383 (8 studies; CI: 0.124 - 0.642; I2 = 58.5%), lower mean arterial pressure -0.182 (5 studies; CI: -0.368 - -0.004; I2 = 9.09%), serum albumin -0.460 (7 studies; CI: -0.702 - -0.271, I2 = 38.53%) and sodium -0.254 (6 studies; CI: -0.509 - 0, I2 = 48.2%). Effects of RAI on outcomes is shown in the Table. Conclusion: Our meta-analysis reveals a 38% incidence of relative adrenal insufficiency among cirrhotics. Despite a high incidence, RAI did not impact outcomes in terms of ascites, hepato-renal syndrome, ICU admissions, and mortality. Table 1. - Effects of relative adrenal insufficiency on outcomes in non-critically ill decompensated cirrhosis Outcomes Number of studies Risk ratio I2 p-value Ascites 6 1.04 (0.90 - 1.19) 0% 0.59 Hepato-renal syndrome 3 1.31 (0.45 - 3.84) 38.52% 0.62 ICU admission 3 1.79 (0.90 - 3.53) 0% 0.09 In-hospital mortality 5 1.63 (0.94 - 2.83) 0% 0.08

Introduction: Eosinophilic esophagitis (EOE) is associated with dysphagia, food impaction. Studies have shown a seasonal variation with increased incidence in summer months. This study was conducted to assess potential seasonal variation in US in the incidence of esophageal food impaction amongst patients with EOE Methods: Retrospective cohort study using the HCUP's Nationwide Inpatient Sample (NIS) database from Jan 2017 to Dec 2019 was conducted. All adults hospitalized with food impaction due to EOE were included in this cohort. A comparison of monthly variation in food impaction amongst EOE patients was assessed at a national level and regional level. Statistical analysis was performed using SPSS version 25 software. Results: During the study period, a total of 4,744 patients (unweighted) >18 years were admitted with impaction, of which 197 (4.2%) had a diagnosis of EOE. The mean age of the cohort was 44.2 years and 23.9% patients were female. Temporal trends of prevalence at national and regional level for food impaction in EOE patients are shown in Figure A and B respectively. No statistically significant seasonal association of food impaction amongst EOE patients was noted at a national level (Table). Similarly, no statistically significant temporal association of food impaction was noted at a regional level, except in the Midwest region during the months of September-October (Table) where a higher incidence of food impaction was noted. Conclusion: A relation between seasonal variation and the diagnosis of EOE has been shown with peak months varying across regions. Such a seasonal variation is primarily proposed due to role of aeroallergens in adults and foods in children. Data regarding a similar seasonal variation in food bolus impaction in EOE is scarce, with few studies being done in regions outside of US, in Sweden, showing a marked seasonal variation with peak incidence in summer months. The present study was aimed to assess such a seasonal variation across different regions in US. We found no such statistically significant variation at a regional level, except in the Midwest region in months of September-October. Our study was limited due to regional distribution available inNIS data not accounting for intra-regional climatic variation, reliance on ICD coding and not taking into account EOE chronicity and treatment. Further studies exploring the association within a climate region would be needed to prove this association and serve to identify a potential therapeutic strategy.Figure 1.: (A) Nationwide seasonal trends of prevalence of food impaction in those with EOE (B) Regional seasonal trends in prevalence of food impaction in those with EOE Table 1. - National and Regional seasonal association of Food Impaction in EOE OR 95% C.I.for OR p value Lower Upper National Jan-Feb 0.214 0.025 1.814 0.157 Mar-Apr 0.276 0.033 2.316 0.235 May-Jun 0.339 0.041 2.824 0.317 Jul-Aug 0.26 0.031 2.188 0.215 Sep-Oct 0.368 0.044 3.063 0.355 Nov-Dec 0.348 0.042 2.897 0.329 Regional Northeast Jan-Feb 0.196 0.019 1.99 0.168 Mar-Apr 0.615 0.07 5.389 0.661 May-Jun 0.475 0.054 4.215 0.504 Jul-Aug 0.278 0.029 2.635 0.265 Sep-Oct 0.336 0.036 3.116 0.337 Nov-Dec 0.453 0.051 4.016 0.477 Midwest Jan-Feb 1.784 0.439 7.253 0.419 Mar-Apr 1.113 0.221 5.606 0.896 May-Jun 0.831 0.165 4.173 0.822 Jul-Aug 1.858 0.457 7.556 0.387 Sep-Oct 5.304 1.505 18.695 0.009 Nov-Dec - - - - South Jan-Feb 0.686 0.295 1.593 0.38 Mar-Apr 0.471 0.189 1.173 0.106 May-Jun 0.789 0.363 1.715 0.55 Jul-Aug 0.617 0.266 1.432 0.261 Sep-Oct 0.776 0.357 1.687 0.523 Nov-Dec - - - - West Jan-Feb 0.342 0.092 1.268 0.109 Mar-Apr 0.631 0.224 1.778 0.384 May-Jun 1.451 0.608 3.462 0.402 Jul-Aug 0.782 0.29 2.108 0.627 Sep-Oct 0.6 0.213 1.69 0.334 Nov-Dec - - - -

IMPORTANCE:No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH).OBJECTIVE:To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis.DESIGN, SETTING, AND PARTICIPANTS:In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021.EXPOSURES:Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care.MAIN OUTCOMES AND MEASURES:The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework.RESULTS:A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2).CONCLUSIONS AND RELEVANCE:Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Combined serum and ascites fluid measurements point to the cause of ascites. For patients with modest edema, a reduced weight-loss target with diuresis may be acceptable.

Introduction: Synchronous triple primary tumors are rarely described in the literature. Here, we present a case of synchronous triple primary tumors consisting of pancreatic neuroendocrine tumor (PNET), sessile serrated adenoma (SSA) and mucosal schwann cell hamartoma (MSCH) of the colon incidentally discovered in an asymptomatic female. Case Description/Methods: We evaluated a 66-year-old White female with an incidental finding of a 15 mm solid heterogeneous pancreatic tail lesion seen on US, performed for evaluation of asymptomatic transaminitis. Her LFTs revealed AST 56 U/L, ALT 69 U/L, total bilirubin 0.5 mg/dl, ALP 68 U/L. She had a history of osteoarthritis and had recently started taking etodolac. Her transaminitis resolved with discontinuation of etodolac. CECT scan confirmed the lesion in pancreatic body. EUS and FNB revealed a well-differentiated, Grade 1, neuroendocrine tumor with immunohistochemistry staining positive for CAM5.2, synaptophysin, chromogranin, and Islet 1 and Ki67 < 1%. Serum chromogranin A level was normal at 31 ng/ml. Gallium-68 PET scan showed moderate Ga uptake in pancreatic body mass and ruled out any distant metastases. Subsequently, screening colonoscopy showed a 2 mm polyp in the ascending colon, which turned out to be SSA. Another, 2 mm polyp in the sigmoid colon was MSCH, positive for S-100 but negative for desmin and EMA on IHC. She was evaluated by genetic counselor. Genetic testing to identify single-gene hereditary predisposition to tumors was negative for mutations in 86 genes. We conservatively managed her with surveillance imaging over six months for neuroendocrine tumor with plans of eventual resection based on patient preference and repeat colonoscopy in a year. Discussion: The incidence of multiple primary GI tumors is increasing, likely due to aggressive screening, improved treatment modalities and surveillance techniques, approaches which have also increased overall life expectancy. Our patient presented with an incidental finding of PNET and was found to have MSCH and SSA on screening colonoscopy. MSCH is a rare benign tumor of schwann cells with 38 cases reported in literature to date, 12 of which were associated with colonic adenomas. To our knowledge, this is the first reported case of MSCH in association with SSA and PNET. There was no identifiable mutation/syndrome to explain the association in the patient. We expect more such cases to be reported in the future, which will help guide appropriate work up and management of multiple primary tumors.Figure 1.: Figure 1A: shows patchy areas of erosions and inflammation that were seen throughout the colon, with rectosigmoid sparing, consistent with colitis. Endoscopic appearance not consistent with any infectious etiology, such as CMV, with negative H&E stain findings. Figure 1B: shows resolution of erosions and inflammation. Five months after withdrawal of Dasatinib therapy.

Introduction: Amyloidosis is characterized by extracellular deposition of insoluble proteins. Primary amyloidosis is a subtype with liver involvement seen in 70% of the cases. Cholestasis is a rare occurrence described by presence of focal amyloid deposition in the bile ducts leading to biliary obstruction. We present an unusual case of amyloidosis presenting with intra and extrahepatic biliary ductal dilation with no evidence of biliary obstruction. Case Description/Methods: A 64 year-old female presented with 3 months of abdominal distension and lower extremity edema. She had a past medical history of cholecystectomy at age 47 and a Roux-en-Y gastric bypass at age 50. Physical examination revealed abdominal distension and gross peripheral edema. Lab work demonstrated ALP 529 U/L, AST 19 U/L, ALT 15 U/L, albumin 1.4 g/dl, total bilirubin 0.2 mg/dl, serum creatinine 1.8 mg/dl. Autoimmune panel returned negative. Liver ultrasound revealed homogenous liver with intra and extrahepatic biliary tree dilation, CBD measuring 15 mm, and moderate amount of ascites. Paracentesis demonstrated SAAG < 1.1 g/dl. This, along with elevated creatinine, raised suspicion for nephrotic syndrome. A renal biopsy was performed that revealed extensive mesangial expansion with amorphous material that stained positive with Congo red suggestive of amyloidosis. Further analysis confirmed AL amyloid (kappa subtype). Further bone marrow biopsy revealed hypercellular marrow, excess of plasma cells and a positive congo red stain confirming amyloidosis. Patient’s ALP increased to 1478 U/L. MRCP revealed moderate to severe intra and extrahepatic biliary dilation with CBD measuring 14-mm without evidence of obstruction. ERCP was not performed and considered challenging given patient’s Roux-en-Y-anatomy. Patient was initiated on chemotherapy with cyclophosphamide, bortezomib and dexamethasone (CyborD) and daratumaab in anticipation of eventual stem cell transplant. Discussion: Intrahepatic biliary dilation has been previously reported as a result of impedance to bile flow due to amyloid deposition. Rare cases of extrahepatic cholestasis have also been reported wherein amyloid presenting as ‘amyloidoma’ results in mass effect causing CBD obstruction. In our case, there was presence of both intra and extrahepatic biliary dilation without laboratory or radiographic evidence of obstruction. Given amyloidosis has a high mortality if left untreated, it is important to consider it in the differential diagnosis for unexplained biliary duct dilation.Figure 1.: Magnetic resonance cholangiopancreatography (MRCP) demonstrating biliary duct dilation without obstruction.

Introduction: Statin therapy is used for both primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). With a concern for hepatotoxicity, there is a reluctance among practitioners to prescribe it in patients with cirrhosis despite AASLD recommending its use in patients with cirrhosis and numerous studies showing beneficial effects on liver related outcomes. We aim to assess the prescription patterns of statins in cirrhotics in primary care physicians (PCPs) and cardiologists via this survey. Methods: A voluntary survey via surveymonkey.com containing 9 objective type questions were sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected and values were expressed as N (frequencies). Chi square test was used to compare the two groups. P value ≤ 0.05 was considered for statistical significance. Results: Overall, 64/220 PCPs (29.1%) and 15/75 (20%) cardiologists completed the survey and were included for final analysis. The results of the survey has been described in Table 1. 10/79 (12.6%) respondents did not prescribe statins to compensated cirrhotics for 1º prevention of ASCVD. 68.5% (48/70) of prescribing practitioners preferred lower intensity of statins. Interestingly, 14.1% (9/64) PCPs avoided statins in compensated cirrhotics for 2º prevention of ASCVD as well. Even though 100% (15/15) cardiologists prescribed statins for 2º prevention of ASCVD in compensated cirrhotics, more than 50% cardiologists preferred lower intensity of statins. Cardiologists were significantly more likely to prescribe statins if cirrhosis was due to NAFLD than other causes (P = 0.05). While 47 % (30/64) PCPs did not have a preference of type of statin, 40% (6/15) cardiologists preferred pravastatin. Only 5/64 (7.8%) PCPs considered statin for improving outcomes in cirrhosis without CV indications. Conclusion: Despite increasing evidence favouring use of statins in cirrhosis for improving portal hemodynamics, decreasing ascites, hepatic encephalopathy, incidence of hepatocellular carcinoma and overall decreasing mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap.Table 1.: Comparison of statin prescription in cirrhosis patients between primary care physicians and cardiologists (N = 79) Abbreviations: PCPs: primary care physicians, ASCVD: atherosclerotic cardiovascular disease, NAFLD: non-alcoholic fatty liver disease.

Introduction: Hemophagocytic Lymphohistiocytosis (HLH) is rare syndrome characterized by a systemic macrophagocytic process triggered by excessive cytokine and immune activation. We present a case of fulminant autoimmune hepatitis leading to HLH. Case Description/Methods: A 30 year old African American woman was admitted with nausea, vomiting, low grade fevers, and abdominal pain for 4 days. Home medications included 3 days of amoxicillin with acetaminophen 2 g daily for dental infection. She denied heavy alcohol use, illicit drug use, and herbal supplementation. Comprehensive laboratory investigation shown on Table 1. Hepatitis A, B, C, E , CMV, EBV, COVID-19, and pan cultures were negative. Hepatospleenomegaly present. After 3 days of IV NAC, aminotransfereases downtrended to a persistent 400-500’s range, however total bilirubin and INR worsened despite Vitamin K administration. Due to clinical suspicion for autoimmune hepatitis, she was started on prednisone 60mg daily. Liver biopsy showed portal and lobular interface hepatitis with focally prominent plasma cells with periportal fibrosis as well as extensive histocyte/macrophage infiltration and activation. Additional labs showed: ferritin 4,014 mg/mL, fibrinogen 94 mg/dL, LDH 1100 U/L, normal triglycerides, elevated IL-2 receptor (6300), and normal NK cell activity. With concern for HLH, a bone marrow biopsy confirmed hypercellular bone marrow with active trilineage hematopoiesis and foci of hemophagocytocytosis. She later developed grade 2-3 hepatic encephalopathy requiring closer monitoring in ICU. Liver transplant evaluation was initiated, but fortunately her clinical status improved with continued steroid use. Azathioprine 50 mg was subsequently started with steroid taper. Her current hepatic function panel remains normal with azathioprine monotherapy. Discussion: HLH has a wide range of clinical presentations, making it difficult to diagnose promptly. The disease has a quick progression and carries a high mortality. HLH subtypes are classified into genetic and acquired etiologies. HLH can be triggered by infections, autoimmune processes, malignancy, and organ transplant with immunosuppressant use. She met 6 of 8 diagnostic criteria, based on the HLH 2004 trial. Although liver failure can be a manifestation of HLH, autoimmune hepatitis likely incited her macrophage activation syndrome. HLH should remain on the differential for patients with unexplained pancytopenia, hepatospleenomegaly, hyperferritinemia, and fevers.Table 1

Introduction: Portal hypertension commonly results in esophageal varices while rarely causing ectopic varices. Among ectopic varices, the stomach and rectum are the most common sites with rare case of cecal varices reported in literature. This case serves to demonstrate the diagnostic and therapeutic challenge of bleeding cecal varices. Case Description/Methods: 59 year female with decompensated hepatic cirrhosis from NASH/hepatitis C was admitted for hepatic encephalopathy and massive hematochezia. EGD showed two large non-bleeding esophageal varices which were banded. Subsequent emergent CT Angiogram of the abdomen and pelvis done due to ongoing bleeding showed no source of bleeding. A limited prep colonoscopy had to be aborted due to colonic edema and tortuosity of the colon. Blood was visualized throughout the examined colon without an obvious etiology for bleeding. A visceral arteriogram showed large cecal varices thought to be the bleeding source [Figure 1]. TIPS procedure resulted in reduction in porto-systemic pressure gradient from 14 mmHg to 3 mmHg with resolution of bleeding. Discussion: While bleeding esophageal varices in a cirrhotic patient are common, bleeding cecal varices are rare. Paucity of data makes diagnosing cecal varices difficult. Absence of esophageal/gastric varices or stigmata of recent bleeding on an initial EGD in those with portal hypertension should prompt evaluation for ectopic varices. Endoscopic visualization is limited during acute hemorrhage due to red out and potential collapse of variceal vessels from over insufflation or hypotension. Thus, most current literature points to selective visceral angiography as the ideal diagnostic modality for diagnosis and therapeutic interventions. When feasible, CT angiogram along with meticulous endoscopic evaluation (in adjunct with endoscopic ultrasound) can also be used. Treatment options for bleeding cecal varices such as vasoactive substance administration and endoscopic therapy, i.e. injection sclerotherapy, have not been well studied. Band ligation is considered unsafe and unfeasible for varices proximal to the rectum. The curative treatment for cecal varices is liver transplant, though generally TIPS procedure is attempted, and case reports have demonstrated the use of venous embolization in cases refractory to TIPS. Surgical interventions such as colectomy have also traditionally been a part of curative treatment that has been reserved for acute cases not responding to less invasive interventions.Figure 1.: Large cecal varices seen on the visceral arteriogram during the indirect portal phase venogram.

WE compared to WC.The expression also exhibited the rhythmicity across the ZT time point.The circadian pattern and the mRNA expression of both Cyp genes were blunted in SKO+E group.Our data suggest that ethanol regulates CYP4A expression through SHP.The circadian rhythmicity of Cyp genes in WE group led us to hypothesize that their expression is under the control of circadian transcriptional regulator.We found the possible binding of REV-ERBa on Cyp4a10 and Cyp4a14 promoters which was confirmed with CHIP assay using anti-REV-ERBa antibody in liver samples from WC and WE group (at ZT 12).To further confirm the regulation of CYP4As by REV-ERB a, we found the significant increase in Cyp4a10 (~8 fold) and Cyp4a14 (~6 fold) in Rev-Erba-/-mice.We asked if activation of REV-ERBa ameliorates alcohol-induced liver injury.We found significantly decreased the mRNA and protein expression of Cyp4a10 and Cyp4a14, serum ALT, and genes involving in lipid metabolism in ethanol-fed mice treated with SR9009 compared to those fed with ethanol alone.Conclusions: We reported a mechanism linking circadian pathway and ALD by identifying a novel SHP-REV-ERB a-CYP4A axis.Activation of REV-ERB a attenuated hepatic steatosis and liver injury from alcohol, suggesting its role as a potential therapeutic target for ALD.

underwent systematic counseling by a physician (MD) and RD on intake.Weight, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and adherence to weight loss strategies were recorded and assessed at a mean of 1.27 years (range 0.25 to 4.3 yr) following the initial visit.Paired sample t-test for paired measurements and point-biserial correlation for dichotomous and continuous variables were used for statistical analysis.Two-tailed p-value <0.05 was considered statistically significant.Results: Of the 76 patients who met inclusion criteria, 45 had at least one visit with an RD and 31 had no RD visits.All patients were seen by an MD or nurse practitioner (NP) throughout follow-up and counseled systematically.Those with at least one RD visit had significant reductions in weight (p=0.002,CI=-6.04 to -1.5), BMI (p=0.01,CI=-1.80 to -0.26), AST (p<0.001,CI=-19.97 to -6.67), and ALT (p<0.001,CI=-33.55 to -11.43) compared to those with no RD visits, who only had significant reductions in AST (p=0.029,CI=-24.09 to -1.49) and ALT (p=0.041,CI=-43.18 to -1.04).Number of RD visits correlated significantly with ‡7% weight loss (p=0.028) as well as utilization of diet trackers (p<0.001) and structured