Normal Bilirubin Levels Research Articles

Hyperbilirubinemia: a new diagnostic marker for perpendicular perforation

Background: Appendicitis is one of the commonest causes of abdominal pain requiring emergency surgery. Diagnosing acute appendicitis clinically still remains a common surgical problem as the clinical signs and symptoms of other abdominal pathologic conditions mimic the diagnosis of acute appendicitis. Delay in diagnosis and surgery for this condition may lead to various complications like perforation, abdominal abscess etc. By knowing perforation prior to the exploration, we can manage the condition very effectively in terms explaining the prognosis of disease, morbidity of surgery, wound infection, and requirement of emergent nature of surgery. Aim of the study is to determine of role of hyperbilirubinemia as a new diagnostic marker to predict gangrenous/perforated appendicitis.Methods: It’s a retrospective study was conducted in the department of surgery, MMCRI, Mysore during the period of January 2015 to December 2015 total of 100 patients with clinical as well as ultrasonographic diagnosis of acute appendicitis or appendiceal perforation were made. The serum bilirubin test was carried out in all the patients pre-operatively.Results: In the study, the total 100 patients enrolled for the study, hyperbilirubinemia (> 1.2 mg/dL) in present study was found in 47 patients with 19 acute and 28 patients perforated appendicitis of all the 100 patients while 53 patients had normal bilirubin levels (≤ 1.2 mg/dL) 51 patients acute and 2 patients perforated appendix.Conclusions: Total serum bilirubin appears to be a new promising laboratory marker for diagnosing appendicular perforation. The patients with clinical signs and symptoms of appendicitis and with hyperbilirubinemia without elevation of liver enzymes should be identified as having a higher probability of appendicular perforation, suggesting total serum bilirubin levels have a predictive potential for the diagnosis of appendicular perforation.

Annals for Educators - 15 August 2017

Annals for Educators - 15 August 2017

A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi

BackgroundMalawi’s national antiretroviral therapy program provides atazanavir/ritonavir–based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi.MethodsWe conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model.ResultsOut of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p < 0.001), although adherence by pill count was similar (62.9% vs. 60.7%, p = 0.804). The odds of virological failure were higher for adults aged 25–40 years (adjusted odds ratio (aOR) 2.5, p = 0.048), those with CD4 cell count <100 (aOR 17.5, p < 0.001), and those with normal bilirubin levels (aOR 5.4, p < 0.001); but were lower for the overweight/obese patients (aOR 0.3, p = 0.026). Poor pill count adherence (aOR 0.7, p = 0.4) and male gender (aOR 1.2, p = 0.698) were not associated with second line virological failure.ConclusionsAmong patients receiving atazanavir/ritonavir-based second line antiretroviral therapy, bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

Percutaneous stenting for transhepatic cholangiojejunostomy

Objective: To describe a new technique that can be used for palliative treatment for unresectable cholangiocarcinoma. Methods: The procedure was performed on a patient with recurrence of IC after two years of a left hepatectomy. Since it was a case of advanced disease with no possibility of resection, we performed a modified Longmire procedure (intrahepatic cholangiojejunostomy). Levels of bilirubin remained elevated after the surgical procedure, we decided to associate an internal drainage using a stent promoting jaundice relief using the preview modified Longmire procedure. Results: Patient remained jaundice free until she died of other complications of the disease after 04 months. During this period of time patients presented normal levels of bilirubin. Did not present acute cholangitis and referred better quality of life since she did not have external drains. Conclusion: We conclude that this technique can be an alternative palliative treatment for patients with advanced cholangiocarcinoma or even in cases of complex benign strictures of the biliary tree.

Validity of Serum Total Bilirubin as a Diagnostic Tool for Acute Appendicitis

Objective: To study the relationship between hyperbilirubinemia and acute appendicitis and to evaluate its credibility as a diagnostic marker for acute appendicitis and to evaluate whether elevated serum total bilirubin levels have a predictive potential for the diagnosis of complicated appendicitis Background: In acute appendicitis occurs through bacterial invasion in appendix leads to transmigration of bacteria and release of TNF-alpha, IL6 and cytokines. These reach the liver through superior mesenteric vein and may produce inflammation or dysfunction of liver either directly or indirectly by altering hepatic blood flow with rising of total serum bilirubin. Methods: This is a prospective cohort study including Ninety four (94) of adult patients have right iliac fossa pain attending to the Emergency Department (ED) at Suez Canal university Hospital. All 94 patients undergo total serum bilirubin measuring and post-operative histopathological examination of removed appendix. Results: In this study population of 94 patients and found that thirty-six male patient (38 %) and fifty-eight female patient (62 %), 81 patients (86.2%) were diagnosed as acute appendicitis while 13 patients (13.8%) were normal post-operatively by histopathological reports. Amongst the patients diagnosed with Acute appendicitis post-operatively, 57 patients (70.4%) were found to have elevated serum total bilirubin (>1.2mg/dL) while 24 patients (29.6%) had normal serum total bilirubin levels (≤1.2 mg/dL). Conclusion: Serum total bilirubin level appears to be a promising new laboratory marker for diagnosing acute appendicitis and have a predictive potential for the diagnosis of complicated appendicitis.

Nodular Regenerative Hyperplasia Associated with Celiac Disease and Limited Sclerosis without Pulmonary Hypertension

Nodular Regenerative Hyperplasia (NRH) is a rare liver disease characterized by a diffuse transformation of the hepatic parenchyma into small regenerative hyperplastic and atrophic nodules, in the absence of fibrosis (1, 2). Due to the lack of major epidemiologic studies, most of the knowledge about NRH has been defined by case series (4). Reports have suggested the immune misbalance in Limited Sclerosis, Celiac Disease, and administration of immunosuppressants as possible causes of Obliterative Portal Venopathy (OPV) and NRH (4, 5). We present the first case to our knowledge, of a patient with OPV/NRH exacerbated by use of Azathioprine in the setting of simultaneous Celiac disease and Limited Sclerosis. Case Report: A 63 year old female presented with progressive increase in abdominal girth, shortness of breath and melena. She denied history of alcohol abuse or toxic exposure. Review of systems was significant for Raynaud's phenomenon, dysphagia and esophageal reflux. CBC showed anemia with normal platelet count. Liver panel showed mild elevation of alkaline phosphatase and normal levels of AST, ALT and bilirubin. Coagulation tests were normal. Viral hepatitis markers were negative. Serology was positive for antinuclear antibody, as well as transglutaminase and gliadin antibodies. At this point, antismooth muscle antibodies (ASMA) titers were 1:20, anti-mitochondrial, and anti-endomysial antibodies were negative. Echocardiogram showed normal ejection fraction with normal pulmonary pressures. CT scan of the abdomen revealed nodular contour of the liver with hypertrophic opacification of the Inferior Vena Cava and evidence of portal hypertension. The patient was clinically diagnosed with cryptogenic cirrhosis, and liver biopsy was arranged. While awaiting the result, she was encouraged to continue medical follow up. During outpatient rheumatologic consult, anti-centromere antibody was positive at high titers, as well as weak ASMA antibody titers. At this point, the patient was started on azathioprine. Two weeks later, she presented again with worsening abdominal distention, shortness of breath and multiple episodes of melena causing fatigue and dizziness. Pathological report of liver biopsy showed portal tracts with lymphoplasmacytic infiltrate, fibrosis, ductular reaction and centrilobular congestion, alternating with regenerative areas without signs of cirrhosis. She was treated with paracentesis, gentle diuresis, variceal banding, gluten restriction and discontinuation of azathioprine. Overall, her condition improved with these measures. Multiple conditions associated with NRH overlap in this case. Liver injury is a rare complication of Limited Sclerosis, Primary Biliary Cholangitis (PBC) being the most commonly reported disease (4). An overlapping syndrome including Limited Sclerosis, PBC and NRH has been established as well (6, 7). This patient had negative anti-mitochondrial antibodies. The liver biopsy findings were consistent with Obliterative Portal Venopathy and Nodular Regenerative Hyperplasia with secondary effect on the biliary tree, likely causing Secondary Sclerosing Cholangitis instead. Interestingly, there were no signs of pulmonary hypertension or extensive vascular damage to justify the development of Portal Venopathy. The clinical presentation, in addition to the weakly positive titers of anti-smooth muscle antibodies, erroneously led to the diagnosis of Autoimmune Hepatitis (AIH). Azathioprine, a mainstay of treatment for AIH, is an immunosuppressant that has been allegedly linked to the progression of NRH, consequently exacerbating this patient's symptoms (8, 9). Additionally, the patient was diagnosed with celiac disease, another disorder that can result in an increased immune reaction in the splenoportal axis of susceptible affected individuals (10, 11, 12). This reinforces that patients with Idiopathic Portal Hypertension should be evaluated for Celiac disease. Nodular Regenerative Hyperplasia appears to be an adaptive response to the vasculopathy that results in injury of the hepatocytes (1, 2), with the potential complications of portal hypertension, liver damage and death. This case highlights the difficulties that may be encountered in determining the etiology and proper treatment for this disease. It is of relevance to obtain a prompt liver biopsy, and an interdisciplinary approach with close communication between specialists. The coexistence of Obliterative Portal Venopathy, Celiac Disease, Limited Sclerosis and exposure to Azathioprine, supports the hypothesis of autoimmune mediation in the development of NRH and Portal Hypertension. With so many variables at play, further research in the field of liver immunology will be necessary to achieve a timely diagnosis and treatment of Nodular Regenerative Hyperplasia.Figure 1Figure 2Figure 3

Temporary Trans-jejunal Hepatic Duct Stenting in Roux-en-y Hepaticojejunostomy for Reconstruction of Iatrogenic Bile Duct Injuries.

BackgroundBile Duct Injuries (BDI) during cholecystectomy are now being recognized as major health problems.ObjectivesHerein, we present our experience with handling major BDIs and report long-term outcome of hepaticojejunostomies followed by trans-jejunal hepatic duct stenting performed to reconstruct extra-hepatic biliary tracts.Materials and MethodsIn this case series, we prospectively collected data of 22 patients, who underwent first time biliary reconstruction through Roux-en-y hepaticojejunostomy followed by hepatic duct stenting using a trans-jejunal bifurcated 6F tube drain. The long-term outcome was assessed and defined as excellent (asymptomatic, normal liver enzymes and bilirubin levels), good (asymptomatic, mild abnormality in liver enzyme and bilirubin levels), poor (symptomatic, abnormal liver enzymes and bilirubin level) and failure (requiring reoperation).ResultsA total of 22 patients including four males (18.1%) and 18 females (81.8%) were evaluated. The mean age was 42.71 (range: 23 - 74) years. Twelve patients had undergone open cholecystectomy (54.5%) and the rest had a history of laparoscopic cholecystectomy. The mean interval between the primary operation and reconstruction was 92.71 days. The mean follow-up period after biliary reconstruction was 42.33 (range: 1 - 96) months. No instance of anastomotic leakage or stenosis, biliary sepsis, thromboembolic event, or respiratory infection was noted in the long-term follow-up. The outcome was excellent in all patients. No case with poor or failure of result was noticed.ConclusionsAlthough a devastating complication iatrogenic major bile duct injuries can be corrected surgically with a high rate of success. Temporary trans-jejunal stenting of the hepatic ducts can help in maintaining the integrity of anastomosis without stenosis or biliary sepsis.

Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

BackgroundTo examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability.ResultsIn patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326–12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509–63.467, P < 0.001), preoperative CA 125 levels ≤26 U/ml (OR 8.209, 95 % CI 2.624–25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma.ConclusionsPreoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) Pancreatitis and Stent Dysfunction after Preoperative Biliary Drainage in Patients with Malignant Biliary Stricture.

Objective To retrospectively evaluate the risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and stent dysfunction after performing preoperative biliary drainage (BD) in patients with malignant biliary stricture. Methods Between January 2003 and February 2013, 105 consecutive patients who had undergone transpapillary BD before surgery were enrolled in this study. Procedure-related complications, stent dysfunction rates, and their respective risk factors were investigated. PEP was defined according to the consensus guidelines. Results Fifty-five patients had bile duct cancer, 31 had pancreatic cancer, 16 had ampullary cancer, and 3 had gallbladder cancer. Endoscopic biliary stenting (EBS) and nasobiliary drainage (NBD) were performed in 84 patients and 21 patients, respectively. PEP occurred in 10% of the patients, with a significantly higher frequency in those with hilar/upper bile duct stricture (p=0.026) and a normal bilirubin level at admission (p=0.016). Of the 84 patients who underwent initial EBS, stent dysfunction occurred in 13%. The mean number of days from EBS to stent dysfunction was 14±12 days. A multivariate analysis revealed a male gender (p=0.048), a stent diameter ≤8 Fr (p=0.036), and an ERCP procedure time ≥45 minutes (p=0.021) to be risk factors for stent dysfunction. No NBD tube dysfunction was observed. Conclusion Patients with upper/hilar bile duct stricture or a normal bilirubin level are at high risk of developing PEP after preoperative BD. NBD or EBS with a large-bore stent is therefore recommended as preoperative BD.

A Case of Ciliated Foregut Cyst of the Gallbladder.

Congenital cysts of the gallbladder are extremely rare, hence only a few ciliated foregut cysts of gallbladder have been reported. We report a case of a 20-year-old woman presenting with mild right upper quadrant abdominal discomfort, with normal levels of serum bilirubin and liver function tests. Abdominal ultrasonography revealed a well-defined cystic mass measured about 2 cm attached to the neck of gallbladder, with internal echogenic debris suggesting a complicated cyst, such as a hemorrhagic cyst. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed similar findings. Laparoscopic cholecystectomy showed a slightly distended gallbladder. The size of cyst on the neck was 1.6×1.2 cm, and it contained mucosa lined by ciliated pseudostratified columnar epithelium and underlying smooth muscle layers. Histopathology identified a ciliated foregut cyst of gallbladder.

Liver function tests in patients with acute heart failure and associated outcomes: insights from ASCEND-HF.

We aimed to characterize abnormal liver function tests in patients with heart failure (HF), as they are commonly encountered yet poorly defined. We used data from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) to characterize associations with baseline liver function tests (LFTs). Each LFT was analysed as both a continuous and dichotomous variable [normal vs. abnormal; bilirubin >1.0 mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >35 mmol/L]. Logistic regression assessed the association of LFTs and 30-day all-cause mortality and HF rehospitalization, and Cox proportional hazards assessed the association with 180-day all-cause mortality among patients alive at a 30-day landmark. In ASCEND-HF, 4228 (59%) had complete admission LFT data. Of these, 42% had abnormal bilirubin, 22% had abnormal ALT, and 30% had abnormal AST. Patients with abnormal LFTs were younger, had lower body mass index, and lower left ventricular ejection fraction. In multivariable models, increased total bilirubin was associated with increased 30-day mortality or HF rehospitalization [hazard ratio (HR) 1.17 per 1 mg/dL increase, 95% confidence interval (CI) 1.04, 1.32; P = 0.012], but not with an increase in 180-day mortality (HR 1.10, 95% CI 0.97, 1.25; P = 0.13) per 1 mg/dl increase. Compared with normal bilirubin levels, abnormal bilirubin was associated with increased 30-day mortality or HF rehospitalization (HR 1.24, 95% CI 1.00, 1.54; P = 0.048) and 180-day mortality (HR 1.32, 95% CI 1.08, 1.62; P = 0.007). We found no association with AST or ALT and outcomes. Greater than 40% of patients hospitalized with acute HF had abnormal LFTs. After multivariable adjustment, only elevated bilirubin was independently associated with worse clinical outcomes and may represent an important prognostic variable.

Low Alpha-Fetoprotein Levels Are Associated with Improved Survival in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis

Macroscopic portal vein thrombosis (PVT) is a common and dire prognostic feature of patients with hepatocellular carcinoma (HCC) and often precludes many treatments as a result. Little is known about its causes or mechanisms or clinical associations. To examine patients with PVT in order to possibly identify prognostically different subsets. A large cohort of non-curable patients with advanced and biopsy-proven HCC in which survival was documented, were retrospectively examined. We analyzed a large HCC cohort containing 366 (63.3%) PVT-positive patients and found that PVT is associated with patients having larger tumors and higher levels of alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP). We identified in patients with normal bilirubin levels (≤ 2.0 mg/dl) two PVT-positive patients, having higher and lower AFP levels, respectively. They differed in the significantly better prognosis of the low AFP patients, which may be useful for patient management decisions. Patients with PVT are heterogeneous with respect to AFP levels. AFP-negative patients have a significantly better survival than those who have elevated AFP.

Malignant biliary strictures in patients with a normal bilirubin and/or normal liver enzymes

BackgroundTo date, no studies have sought to determine the frequency of malignancy in patients presenting with a putative biliary stricture and normal liver function tests (LFTs). The primary aim of this retrospective cohort study was to determine the likelihood of malignancy in patients presenting with a biliary stricture and normal LFTs, a normal bilirubin level either alone or in combination with normal levels of liver enzymes [alkaline phosphatase (ALP) and alanine transaminase (ALT)]. A secondary aim was to determine any clinical/biochemical/sonographic features that may be associated with malignancy. MethodsPatients presenting over a 10‐year period were included. Fifteen variables were analysed to determine their association with malignant disease. ResultsEight hundred and thirty patients with putative biliary strictures were included. Primary hepatopancreaticobiliary (HPB) cancers presented with a normal bilirubin and normal liver enzymes (ALP and ALT) in 6% of cases. Patients with a putative biliary stricture and a normal bilirubin level whose final diagnoses were pancreatic cancer, ampullary cancer, distal cholangiocarcinoma and hilar cholangiocarcinoma represented 21%, 13%, 7% and 9% of individuals diagnosed with these pathologies, respectively. Hypoalbuminaemia and isolated intrahepatic duct dilatation on ultrasound were significantly associated with malignancy in patients with normal bilirubin and completely normal LFTs. ConclusionsThis study has shown that patients with a putative biliary stricture and completely normal LFTs are unlikely to have a primary HPB malignancy. Those presenting with a normal bilirubin level, but deranged liver enzymes (ALP and/or ALT), are more likely to have malignant disease, and this should necessitate a higher degree of clinical suspicion.

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

BackgroundThe prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described. MethodsPre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. ResultsPre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. ConclusionsAmong patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic.

Multicenter Experience with Boceprevir or Telaprevir to Treat Hepatitis C Recurrence after Liver Transplantation: When Present Becomes Past, What Lessons for Future?

Background and aimsFirst generation protease inhibitors (PI) with peg-interferon (PEG-IFN) and ribavirin (RBV) have been the only therapy available for hepatitis C virus (HCV) genotype 1 infection in most countries for 3 years. We have investigated the efficacy and tolerance of this triple therapy in transplanted patients experiencing a recurrence of HCV infection on the liver graft.PatientsThis cohort study enrolled 81 liver transplant patients (Male: 76%, mean age: 55.8±9.7 years) with severe HCV recurrence (F3 or F4: n = 34 (42%), treatment experienced: n = 44 (54%)), treated with boceprevir (n = 36; 44%) or telaprevir (n = 45; 56%). We assessed the percentages of patients with sustained virological responses 24 weeks after therapy (SVR24), and safety.ResultsThe SVR24 rate was 47% (telaprevir: 42%; boceprevir: 53%, P = ns). At baseline, a normal bilirubin level (p = 0.0145) and albumin level >35g/L (p = 0.0372) and an initial RBV dosage of ≥800 mg/day (p = 0.0033) predicted SVR24. During treatment, achieving an early virological response after 12 weeks was the strongest independent factor to predict SVR24 (p<0.0001). A premature discontinuation of anti-HCV therapy due to a serious adverse event (SAE) was observed in 22 patients (27%). Hematological toxicity, infections and deaths were observed in 95%, 28% and 7% of patients, respectively. A history of post-LT antiviral therapy and thrombocytopenia (<50G/L) during treatment were both independent predictors of the occurrence of infections or SAE (p = 0.0169 and p = 0.011).ConclusionsThe use of first generation PI after liver transplantation enabled an SVR24 rate of 47% in genotype 1 patients, but induced a high rate of SAE. The identification of predictive factors for a response to treatment, and the occurrence of SAE, have enabled us to establish limits for the use of this anti-HCV therapy in the transplant setting.

Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from Grade 3 Gastroenteropancreatic Neuroendocrine Tumors.

Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare, and there is no report specifically dealing with patients of liver metastases from G3 GEP NETs.From January 2004 to January 2014, 36 conservative patients with G3 GEP NET liver metastases were retrospectively identified from 3 hepatobiliary centers in China. The clinical features and treatment outcomes were analyzed.Aggressive locoregional treatments (LT, including cytoreductive surgery, radiofrequency ablation, and liver-directed intra-arterial intervention) and systemic therapy (ST) were introduced separately or combined, with 26 (72%) patients receiving resection of primary tumor and/or hepatic metastases, 12 patients receiving non-surgical locoregional interventions (NSLRIs), and 22 patients receiving certain kind of STs. Median overall survival (OS) was 20.0 months (95% confidence interval [CI]: 8.9–31.1 months) and survival rates were 62.6%, 30.1%, and 19.8%, at 1, 3, and 5 years, respectively. The median OS was 9.0 months (95%CI: 3.3–14.7 months) for patients receiving only STs (n = 6), 19 months (95%CI: 1.3–36.8 months) for patients receiving LT followed by STs (n = 16), and 101 months (95%CI: 0.0–210.2 months) for patients receiving only LT (n = 12). Moreover, compared with those receiving only ST or best supportive care, patients given certain types of LTs had higher rates of symptom alleviation (3/8 versus 20/23). On univariate analysis, positive prognostic factors of survival were pancreatic primary tumor (P = 0.013), normal total bilirubin level (P = 0.035), receiving surgery (P = 0.034), receiving NSLRI (P = 0.014), and sum of diameters of remnant tumor < 5 cm (P = 0.008). On multivariate analyses, pancreatic primary tumor (P = 0.015), normal total bilirubin level (P = 0.002), and sum of diameters of remnant tumor < 5 cm (P = 0.001) remained to be independent prognostic factors.For patients with G3 GEP NET liver metastases, aggressive LTs may improve clinical outcomes. Larger studies with prospective design are warranted to consolidate these results, and to discover the most appropriate seletion criteria for patients to undergo different kinds of aggressive LTs and to find the most effective combinations, with or without ST.

Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?

Role of Bilirubin in Diabetic Vascular Complications: Can Bilirubin Predict More than Just Liver Disease?

Patient with constrictive pericarditis (RCD code: III)

52-year-old Caucasian man was admitted with clinical symptoms of chronic heart failure. Constrictive pericarditis was suspected almost 9 years before admission, but Patient refused to diagnosis. Peripheral oedema, ascites, hepatomegaly, increased jugular venous pressure and pleural effusion were present on admission. Laboratory test showed increased level of Brain Natriuretic Peptide with normal levels of liver enzymes and total bilirubin. Chest X-ray revealed calcifications of pericardium, in echocardiography biatrial enlargement was present with septal bounce, dilated inferior vena cava, respiratory variation of mitral and tricuspid inflow. Computed tomography showed massive calcifications of pericardium and hydrothorax of both pleural cavities. Cardiac magnetic resonance confirmed enlargement of both artia with dyssynchrony of intraventricular septum’s motion and pericardium thickening. Cardiac catheterization confirmed diagnosis of constrictive pericarditis. Patient was qualified for pericardiectomy. He died during procedure due to bleeding complications. According to ESC Guidelines, pericardiectomy is the treatment of choice in patients with significant symptoms with mortality rate 6-12%.

Clinical manifestations and complications of scrub typhus: A hospital-based study from North Andhra

Aims and Objectives: To describe the diversity of clinical manifestations, laboratory findings, and outcome of scrub typhus in hospitalized patients of Tirumala Hospital, Vizianagaram, during 2014–2015. Materials and Methods: All cases of acute febrile illness diagnosed as scrub typhus were analyzed. Diagnosis was made by ELISA-based IgM serology. Observations and Results: A total of sixty patients were included in the study. All of them presented with fever; the other major symptoms were headache, cough, dyspnea, and myalgias. On examination, patients had hepatosplenomegaly, lymphadenopathy, and eschar. On investigation, elevated serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase with normal and elevated bilirubin levels were the most common findings. Other laboratory findings were thrombocytopenia and deranged renal function tests.Other complications were multiorgan dysfunction syndrome, acute respiratory distress syndrome, hypotension, and meningoencephalitis. Majority responded to doxycycline. Conclusion: Scrub typhus though prevalent is under-reported in our country. It should be considered as an important differential diagnosis in a febrile patient with thrombocytopenia, deranged liver or renal functions, Early diagnosis and appropriate treatment is rewarding and prevents morbidity and mortality.

Polymorphism of UGT1A1 and Frequency of Hyperbilirubinemia in Patients with Chronic Myeloid Leukemia Treated By Nilotinib

Background. Isolated hyperbilirubinemia mostly of indirect bilirubin fraction is diagnosed in patients with polymorphism of UGT1A1 gene (Gilbert’s syndrome), mainly homozygous genotype (TA)7/(TA)7 which encodes the enzyme uridinediphosphoglycosyltransferase 1 (UDP-GT) in hepatocytes. Hyperbilirubinemia is also frequent laboratory abnormality in chronic myeloid (CML) patients treated by nilotinib. Connection of hyperbilirubinemia with UGT1A1 polymorphism in CML patients on nilotinib therapy requires understanding and studying.Aims. To estimate the correlation between polymorphism of UGT1A1 gene and frequency of hyperbilirubinemia in patients with CML treated by nilotinib.Methods. We estimated biochemical parameters in a group of 100 patients treated by nilotinib: bilirubin, transaminases (AST, ALT), persistence of hyperbilirubinemia and biochemical parameters normalization. We also considered patients’ anamnesis for hepatitis and estimated those laboratory abnormalities in previous imatinib therapy as 98 of 100 patients received nilotinib second line after imatinib.Me time of observation on nilotinib therapy was 36.7 months (range 1 – 94.5).Men/women ratio was 45/55. Promoter region of the UGT1A1 gene was studied by allele specific polymerase chain reaction (AS-PCR).Results. Hyperbilirubinemia due to the indirect bilirubin fraction was observed in 84 (84%) of 100 patients. Of those 84 patients hyperbilirubinemia grade 1 was in 41 (49%), grade 2 in 33 (39%), grade 3 in 10 (12%). Normal genotype (TA)6/(TA)6 was in 71 (71%) patients, heterozygous genotype (TA)6/(TA)7 in 19 (19%), homozygous genotype (TA)7/(TA)7 in 10 (10%) patients. Frequency of hyperbilirubinemia grade 1-3 in patients depending on genotype is presented in table1. [Display omitted] Hyperbilirubinemia grade 1 was associated mostly with normal genotype patients, grade 2 with normal and abnormal genotype, grade 3 with abnormal and homozygous genotype (9 of 10 patients). In 1 patient with normal genotype grade 3 hyperbilirubinemia was due to intracellular hemolysis approved by laboratory tests. One patient with heterozygous form (TA6/TA7) and normal bilirubin was on nilotinib <1 month.Hyperbilirubinemia on previous imatinib treatment was in 29 (35,7%) of 82 patients with second line nilotinib: grade 1 in 25 (86.2%) of 29 patients (homozygous genotype TA7/TA7 in 5 of 25), grade 2 in 4 (13.8%) of 29 patients (all with homozygous genotype TA7/TA7). Normal bilirubin levels were in 55(46,3%) of 82 patients on previous imatinib therapy. One patient with TA7/TA7 genotype received nilotinib as first line.Bilirubin levels normalized in 48 (57.2%) of 84 patients during 1 to 3 months and persisted in 36 (42.8%).In 8(9,5%) of 84 patients transient ALT and AST elevation was observed: grade 1(1), grade 2 (5) grade 3-4(2); it was resolved and only isolated hyperbilirubinemia was observed later on. In 2 of 84 patients hepatitis C was diagnosed.No treatment discontinuation was done due to hyperbilirubinemia.Summary/Conclusion. In CML patients on nilotinib treatment Grade 3 hyperbilirubinemia as well as previous history of hyperbilirubinemia any grade on imatinib can be a sign of homozygous genotype TA7/TA7. Lower grades of hyperbilirubinemia occur both in patients with normal and abnormal heterozygous genotype. Other reasons for hyperbilirubinemia (hemolysis, hepatitis) should be assessed. No connection of UGT1A1 polymorphism and transaminase (ALT,AST) elevation was established. DisclosuresChelysheva:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis International AG: Consultancy, Honoraria. Turkina:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis International AG: Consultancy, Honoraria.