Abnormal Liver Function Test Results Research Articles

Portal biliopathy: imaging manifestations on multidetector computed tomography and magnetic resonance imaging

Portal biliopathy refers to biliary abnormalities secondary to extrahepatic portal vein obstruction and cavernous transformation and is caused by vascular compression from peribiliary collateral vessels, producing segmental stenoses of the common bile duct and abnormal liver function test (LFT) results.A review of imaging studies yielded 18 patients with abnormal LFT results, biliary tract dilatation, and extrahepatic portal vein obstruction with cavernous transformation. Multidetector computed tomography and magnetic resonance imaging showed biliary stenotic segments in 11 patients secondary to extrinsic compression from enlarged peribiliary collaterals. Clinical and imaging follow-up demonstrated improvement in LFT results with minimal decrease in bile duct dilatation, eliminating percutaneous or endoscopic biliary intervention.

Distinct immunoregulatory cytokine pattern in Egyptian patients with occult Hepatitis C infection and unexplained persistently elevated liver transaminases

Background/Aim:The immunopathogenesis of occult Hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro- and anti-inflammatory activity. This work aimed at studying the serum Th1 and Th2 cytokine production in patients with occult HCV infection.Materials and Methods:Serum levels of cytokines of Th1 (interleukin [IL]-2, INF-γ) and Th2 (IL-4) were measured in 27 patients with occult HCV infection and 28 patients with chronic hepatitis C infection.Results:The levels of IL-2 and interferon-γ were highly significantly increased in patients with chronic HCV infection (P<0.001). IL-4 was highly significantly increased in occult HCV infection (P<0.001). Significant increases were noted in chronic HCV infection regarding bilirubin (P<0.001), ALT (P = 0.009), AST (P = 0.013), AFP (P<0.001), while serum albumin was significantly higher in occult HCV infection (P<0.001). Necroinflammation (P<0.001), fibrosis (P<0.001), and cirrhosis (P = 0.03) were significantly increased in chronic HCV infection.Conclusion:Our data revealed a high prevalence of occult HCV infection (25%) in patients with unexplained persistently abnormal liver function test results. Those patients exhibited a distinct immunoregulatory cytokine pattern, favoring viral persistence and explaining the less aggressive course of this disease entity than chronic HCV infection.

Abnormal Liver Function Tests as Predictors of Adverse Maternal Outcomes in Women With Preeclampsia

ObjectivesTo evaluate whether (1) the absolute magnitude of liver function test values, (2) the percentage change in liver function test values over time, or (3) the rate of change in liver function test values over time predicts adverse maternal outcomes in women with preeclampsia. MethodsWe used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a prospective multicentre cohort study assessing predictors of adverse maternal outcomes in women with preeclampsia. Women with at least one liver function test performed at the time of hospital admission were included. Liver functions were tested by serum concentrations of aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), albumin, total bilirubin, and the international normalized prothrombin time ratio. Parameters investigated were absolute levels, change within 48 hours of hospital admission, change from admission to delivery or outcome, and rate of change from admission to delivery or outcome of each liver function test. The ability of these parameters to predict adverse outcomes was assessed using logistic regression analyses and by calculating the receiver operating characteristic (ROC) area under the curve (AUC). ResultsOf the 2008 women, 1056 (53%) had at least one abnormal liver function test result. The odds of having an adverse maternal outcome were higher in women with any abnormal liver function test than in women with normal results. When test results were stratified into quartiles, women with results in the highest quartile (lowest quartile for albumin) were at higher risk of adverse outcomes than women in the lowest quartile for all parameters (highest for albumin). The absolute magnitude of AST, ALT, and LDH predicted adverse maternal outcomes (AST: ROC AUC 0.73 [95% CI 0.67 to 0.97]; ALT: ROC AUC 0.73 [95% CI 0.67 to 0.79]; LDH: ROC AUC 0.74 [95% CI 0.68 to 0.81]). Neither change of liver function test results, within 48 hours of admission or from admission to delivery or outcome, nor rate of change were predictive. ConclusionWe found abnormal liver function test results to be associated with an increased risk for adverse maternal outcomes. Levels of AST, ALT, and LDH were found to be modestly predictive of these outcomes.

Minimizing hepatic trauma with a novel liver retraction method: a simple liver suspension using gauze suture

Prolonged liver retraction during radical gastrectomy for adequate exposure of the hepatogastric ligament may lead to hepatic trauma. The authors offer a new minimally traumatic liver retraction method using a simple liver suspension with a gauze suture and compare it with the modified liver-puncture method. This study retrospectively evaluated 92 patients who underwent the liver-suspension or liver-puncture method during gastric resections in 2010. Their clinical and operative characteristics were analyzed together with perioperative transaminases, and the two groups were compared. Patients with a history of liver disease, abnormal preoperative liver function test results, postoperative complications, or combined operations were excluded from the study. The liver-suspension method was performed using two 4 × 4-in. gauze pads threaded with a 2-0 Prolene suture, which were secured to the pars condensa with surgical clips and externally tied to suspend the liver toward the abdominal wall. Each liver retraction was completed without intraoperative complications. The patients in the liver-suspension group had more nonhepatic comorbidities than those in the liver-puncture group (P = 0.029). Other patient characteristics such as age, gender, and body mass index (BMI) did not differ between the two groups. No differences were found between the groups in terms of mean operative time (200.3 ± 66.9 vs 214.9 ± 74.4) or preoperative mean alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels. However, the patients in the liver-suspension group had significantly lower postoperative mean ALT levels (postoperative days 0, 1, 2, 3, and 5) and mean AST levels (postoperative days 0 and 1). Compared with the liver-puncture method, the authors' novel liver-suspension with suture-gauze technique is a safe and effective method for retracting the liver during laparoscopic and robotic upper abdominal surgeries.

Elevated International Normalized Ratio associated with long-term azithromycin therapy in a child with cerebral palsy

A case of coagulopathy in a pre-adolescent with cerebral palsy that developed after chronic prophylactic antibiotic use is reported. An 11-year-old boy with cerebral palsy was brought to the emergency department experiencing restlessness and decreased oxygen saturation. Evaluation of the patient revealed gallstone-related pancreatitis, with elevated serum amylase and lipase concentrations and abnormal liver function test results. At the time of the initial evaluation, the International Normalized Ratio (INR) was 6.54 (normal range, 0.8-1.2), and the activated partial thromboplastin time was 53.8 seconds (normal range, 24.4-34.8 seconds). The boy's medication history included use of azithromycin 200 mg every other day for about two years for antiinflammatory therapy. On confirmation of the elevated INR 2 hours after the initial evaluation, azithromycin was discontinued, and a single dose of phytonadione 2 mg was administered. About 14 hours after phytonadione administration, the INR had declined to 0.94; 43 hours later, the INR remained within the normal range without further phytonadione therapy. Using the probability scale of Naranjo and colleagues, this case was rated as a probable drug-related adverse event. Previous reports have linked the development of vitamin K deficiency and impaired coagulation to long-term antibiotic use, but not specifically to use of azithromycin or other macrolide antibiotics. An elevated INR in a child with cerebral palsy was evidently related to long-term therapy with azithromycin. The abnormal INR normalized after discontinuation of azithromycin and administration of one dose of phytonadione.

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = -0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.

Anidulafungin for the treatment of invasive candidiasis

Candidaemia/invasive candidiasis (C/IC) is the most frequently occurring invasive fungal infection worldwide, with a particularly strong impact and high incidence in the intensive-care unit, where there is a need for new treatment options and strategies. The echinocandin anidulafungin has broad in vitro activity against a wide range of Candida species, along with favourable pharmacokinetics that allow administration in hepatic and renal impairment and with any comedication without the need for dose adjustments. The efficacy and safety of anidulafungin for the treatment of C/IC were demonstrated in a number of clinical studies and by some limited data from clinical practice. In a randomized comparative trial for the treatment of C/IC in adults, 76% of patients receiving anidulafungin and 60% of those given fluconazole were treated successfully (95% CI for difference: 4–27; p 0.01). Post hoc analyses suggest that anidulafungin is significantly more effective than standard-dose fluconazole for the treatment of candidaemia in critically ill patients. Anidulafungin is generally well tolerated, with commonly reported side effects including headache, hypokalaemia, gastrointestinal symptoms, abnormal liver function test results, and rash. In pharmaco-economic analyses, anidulafungin compared favourably with fluconazole (in terms of overall costs and hospital resource use) as well as with other echinocandins. Echinocandins, including anidulafungin, are now generally recommended as first-line therapy in moderately to severely ill patients, those with prior azole exposure, and patients with C/IC caused by Candida glabrata or Candida krusei.

Reduced Mortality Rates Following Elective Percutaneous Liver Biopsies

Estimates of complication rates following elective percutaneous liver biopsy vary and might not accurately reflect current practice. We studied mortality and complication rates, by indication, in patients after they underwent liver biopsies. We performed a study using hospital episode statistics collected by the National Health Service in England from 1998 to 2005 of elective percutaneous liver biopsies; data were linked with those from the Office for National Statistics to determine mortality rates. Using data from 61,187 people who underwent liver biopsies, all-cause mortality at 7 and 30 days after biopsy, 7-day mortality directly related to liver biopsy, and episodes of bleeding up to 7 days after biopsy were determined. Overall all-cause mortality by 7 days after biopsy was 2 per 1000 biopsies (95% confidence interval, 1.8-2.5); this rate varied markedly by indication for biopsy, with rates as high as 12 per 1000 for patients investigated for cancer. Death within 7 days directly related to liver biopsy occurred, at most, every 1 in 10,000 biopsies in patients investigated for liver disease or abnormal liver function test results. Overall, 6 episodes of major bleeding occurred per 1000 biopsies. All-cause mortality risk following elective percutaneous liver biopsy is approximately 0.2%, with a higher risk of major bleeding. Deaths directly related to liver biopsy occur approximately 1 in every 10,000 biopsies. This risk is substantially lower than that of previous reports, indicating that the safety of this procedure has improved.

Infliximab-Induced Psoriaform Rash

Infliximab-Induced Psoriaform Rash

Toxic Hepatitis Induced by Show-Wu-Pian, a Chinese Herbal Preparation

Herbal preparations are widely available and often regarded by the public as harmless remedies for a variety of medical ailments. However, some of these products or their metabolites can cause adverse effects such as liver damage. In this case report a 53-year-old female taking shou-wu-pian for 8 months presented with acute hepatitis. Histopathological assessment of liver tissue obtained by biopsy was consistent with a toxic reaction. Clinical and biochemical resolution was brought about following cessation of the drug. It is important for clinicians to consider Chinese herbal preparations as a potential cause of abnormal liver function test results.

Detection of Occult Hepatitis C and Hepatitis B Virus Infections from Peripheral Blood Mononuclear Cells

Purpose: To investigate the problem of occult HCV & HBV infections in patients with persistently longstanding abnormal liver function test results of unknown etiology and to investigate occult HCV in patients with sustained virological response (SVR). Methods: The study included two groups; first group included 40 patients with persistently longstanding abnormal liver function test, in addition to 62 patients with history of hepatitis C who developed SVR. HCV RNA status was tested in serum by conventional RT-PCR and by real-time PCR in Peripheral Blood Mononuclear Cells (PBMCs). HBV DNA in PBMCs was done in first group only. Results: In first group, PCR in PBMCs was positive for HCV RNA in 4 patients with elevated liver enzymes and HBV DNA was positive in PBMCs in 3 patients. In patients with SVR, 7 patients were positive for HCV RNA in PBMCs. Conclusions: Patients with long-standing abnormal results of liver-function tests with unknown etiology may have HCV RNA or HBV DNA in their PBMCs in the absence of anti-HCV antibodies, HBV markers, serum HBV DNA and serum HCV RNA.In Patients with SVR, HCV RNA in PBMCs is recommended to detect residual infection especially in those with high serum HCV RNA levels before treatment.

Hyperchloremic Metabolic Acidosis Due to Deferasirox in a Patient with Beta Thalassemia Major

To report a case of hyperchloremic metabolic acidosis in a patient with beta thalassemia major secondary to treatment with deferasirox due to iron overload. A 58-year-old white female with beta thalassemia major was admitted with fever, fatigue, abnormal liver function test results, and hyperchloremic metabolic acidosis (lactate dehydrogenase 494 U/L, aspartate aminotransferase 167 U/L, alanine aminotransferase 250 U/L, gamma-glutamyl transferase 102 U/L, total bilirubin 3.79 mg/dL, direct bilrubin 2.37, potassium 3.3 mEq/L, PO(2) 81.4 mm Hg, PCO(2) 29.4 mm Hg, HCO(3) 16 mEq/L, pH 7.35, chloride 116 mEq/L, anion gap 7.5 mEq/L). Twenty-five days before admission the patient decided to discontinue treatment with deferoxamine for chronic iron overload and continue treatment with oral deferasirox 1500 mg/day. Despite extended clinical and laboratory examination, no obvious cause of fever, hepatitis, or hyperchloremic metabolic acidosis was revealed. Diagnosis was compatible with tubular dysfunction, drug-induced hepatitis, and hypersensitivity reaction due to deferasirox. All pathological findings were fully reversible and our patient had an excellent outcome. The presence of tubular dysfunction should be considered in any patient with otherwise unexplained hyperchloremic metabolic acidosis. In our patient, other potential causes of metabolic hyperchloremic acidosis were ruled out. Toxic effects of deferasirox are probably caused by chelation of mitochondrial iron, leading to adenosine triphosphate depletion in tubular epithelial cells. Use of the Naranjo probability scale revealed that the adverse reaction was probable. Kidney toxicity may be a major issue in the management of patients receiving deferasirox. Our case indicates a potential risk of renal toxicity with the presence of tubular dysfunction and hyperchloremic metabolic acidosis in patients undergoing treatment with deferasirox.

Acute liver failure caused by concurrent autoimmune hepatitis and hepatitis B in a 16-year old girl

A 16 year-old girl was admitted to hospital because of fatigue and somnolence, nausea, epistaxis and jaundice. Physical examination revealed jaundice, an enlarged liver and tenderness of upper right abdomen. Laboratory tests revealed an increased level of acute liver failure, bilirubin, bile acids, GGTP and a decreased prothrombin ratio, with elevated gamma-globulin and IgG levels, and the presence of anti-mitochondrial M2 antibodies and HBV infection markers. The patient was diagnosed with liver failure resulting from chronic hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 × 10(5) IU/mL and mutations I 204 and I 80), the treatment was modified by adding entecavir. After one month the patient was discharged in good clinical condition, with the recommendation of continued entecavir, prednisone and azathioprine. In subsequent months, no clinical deterioration or abnormal biochemical liver function test results were found, despite the discontinuation of immunosuppressive therapy after 10 mo. The patient continues entecavir therapy.

Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C

Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function. The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB) or C (CHC). We enrolled 2539 Taiwanese adults without CHB or CHC (age range: 16-88 years old) and investigated the factors related to MS using the NCEP-ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria; body mass index (BMI) was measured using Asia-Pacific criteria. The prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the modified ATP III criteria and 15.4% using the International Diabetes Federation criteria. Males had a significantly higher prevalence rate than females (P<0.001), and subjects with MS were significantly older and had significantly higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate analyses, the abnormality of liver function test results were related to gender, level of fasting sugar, systolic blood pressure, triglyceride, high-density lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male gender, a higher BMI value and MS were related to abnormal liver function test results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and 18 IU l(-1) for female. The prevalence of MS in Taiwanese adults without hepatitis B or C was found to be high, and MS and BMI were identified as being related to abnormal liver function test results in these adults.

Type 1 Congenital Extrahepatic Portosystemic Shunt

Congenital extrahepatic portosystemic shunts (CEPS) are rare. Only 60 to 70 cases are reported in the literature. 1 Afflicted patients have a wide range of ages, from 31 weeks in utero to 76 years. Morgan and Superina 2 proposed a classification system for these shunts in 1994 that placed these anomalies into 2 classes. A type 1 shunt is associated with aplasia of the intrahepatic portal system, whereas a type 2 shunt has an intact intrahepatic portal system. The type 1 CEPS has a female predominance, whereas the type 2 CEPS has no sex predilection. A CEPS is important to recognize for several reasons. First, there is a strong association with cardiac, urinary tract, and skeletal anomalies as well as biliary atresia and polysplenia. 1 Second, substantial mesenteric shunting results in elevated levels of toxins and ammonia, causing encephalopathy and central nervous system damage. Third, there is an increased incidence of hepatic tumors, including hepatocellular carcinoma, hepatoblastoma, and sarcoma. Most cases of CEPS are discovered in the postnatal period, when imaging is done while investigating a cardiac anomaly or abnormal liver function test results. The remainder are discovered during evaluation of patients with hepatic encephalopathy and hyperammonemia. Here we report a case of a type 1 CEPS detected by sonography associated with portal venous atresia.

Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized, open-label, parallel-group study

Background : Elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations are highly atherogenic, especially the small, dense LDL (sdLDL) species. Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin, anantihyperlipidemic agent, has been reported to reduce plasma total cholesterol (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile. Objective : The aim of this study was to compare the effects of fenofi brate and atorvastatin on standard lipid concentrations and the LDL profile. Methods : In this randomized, open-label, parallel-group study, men and women aged 18 to 79 years with type II primary dyslipidemia, defined as LDL-C ≥160 and TG 150 to 400 mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were randomized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo) B (reflecting the LDL particle number) in each LDL subfraction prepared by ultracentrifiigation were determined at baseline and after 12 weeks of treatment. Tolerability was assessed using adverse events (AEs) obtained on laboratory analysis and vital sign measurement. Adherence was assessed by counting unused drug supplies. Results : A total of 165 patients (117 men, 48 women; mean [SD] age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to receive atorvastatin (n = 81) or fenofibrate (n = 84). Compared with fenofibrate, atorvastatin was associated with a significantly greater mean (SD) percentage decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C (35.4% [15.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin, fenofibrate was associated with a significantly greater decrease in TG (37.2% [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL-C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen concentration was significantly different between the 2 groups ( P = 0.002); it was decreased with fenofibrate use (4.6% [23.7%]) and was increased with atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL distribution; it was associated with a homogeneous decrease in cholesterol and apoB concentrations in all subfractions, whereas fenofibrate was associated with a marked movement toward a normalized LDL profile, shifting the sdLDL subfractions toward larger and less atherogenic particles, particularly in those patients with baseline TG ≥200 mg/dL. No serious AEs related to the study treatments were reported. A total of 5 AEs were observed in 8 patients, including: abdominal pain, 3 patients (2 in the atorvastatin group and 1 in the fenofibrate group); abnormal liver function test results, 1 (fenofibrate); increased creatine Phosphokinase activity, 2 (atorvastatin); gastrointestinal disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate). Conclusion : In these dyslipidemic patients, fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C, particularly in patients with elevated TG concentration, whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations.

An algorithm for the treatment of the biliary complications of hepatic hydatid disease

Aim: The treatment of hepatic hydatid disease (HHD) is currently standardized. Biliary complications of HHD complicate both the treatment and course of the disease. Several investigations have been performed on the biliary complications of HHD and their treatment. We propose an algorithm for the treatment of the biliary complications of HHD based on our experience. Materials and methods: We investigated 148 patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) due to complicated HHD between January 2000 and December 2006 at the endoscopy unit of the Department of Surgery of Atatürk University Medical School. Age, sex, indications for ERCP and endoscopic sphincterotomy (ES), ERCP findings, laboratory data, operative findings, postoperative complications, and additional interventions (surgical or percutaneous) were noted. Results: Twenty-six patients had not previously undergone surgery for HHD. While 23 of these patients underwent ERCP preoperatively, 3 underwent ERCP during both the pre- and postoperative periods. The remaining 122 patients underwent surgery for HHD and ERCP during the postoperative period. Indications for preoperative ERCP were cholangitis and various clinical signs of cysto-biliary communication (CBC), such as abnormal liver function test results (bilirubin, ALT, AST, GGT, and ALP), biliary colic, and obstructive jaundice. In this group of patients ERCP/ES was not successful in 2 patients that underwent surgery due to emergent circumstances, and another 3 patients developed postoperative biliary fistulae. Indications for postoperative ERCP were persistent bile leakage after surgical treatment for HHD, postoperative hyperbilirubinemia and cholangitis, and postoperative biloma formation in the cystic cavity. All patients with cholangitis experienced relief of symptoms after ERCP and ES, 1 patient with biloma formation and 5 patients with persistent biliary fistulae were operated on. Conclusion: ERCP and ES are highly effective in the treatment of the biliary complications of HHD. Repeat ERCP should be performed in patients that do not respond to the first intervention.

Cystic Duct Stump Leaks

To describe a series of patients who have had cystic duct stump leaks (CDSLs) after laparoscopic cholecystectomy and to compare the current presentation and management with that in previous studies. Two-institution retrospective case series and review of the previously published literature. Two teaching hospitals. Twelve patients who had CDSLs of 5751 patients who underwent total laparoscopic cholecystectomy. Symptoms at presentation, laboratory values, imaging modalities, treatment modalities, and operative indications and techniques. Between January 1, 1998, and March 31, 2007, 12 patients (0.21%) developed CDSLs a mean of 2.3 days postoperatively. Five patients (42%) were reported to have abnormal cystic ducts. A mean of 3 surgical clips were used for closure. Abdominal pain (58%) was the most common presenting symptom; 9 patients (75%) had an elevated white blood cell count, and 9 (75%) had abnormal liver function test results. Ten patients (83%) underwent endoscopic retrograde cholangiopancreatography (ERCP), and 8 (67%) were definitively treated with ERCP stenting of the common bile duct. Two patients (17%) required adjunctive computed tomography-guided drainage. There was 1 death. A CDSL can occur for a variety of reasons. Any patient with a postoperative picture consistent with a bile leak should undergo ERCP. If a CDSL is discovered, the common bile duct should be stented. Computed tomography-guided drainage is indicated if the patient does not improve after ERCP. Operative intervention should be reserved for the most serious of circumstances.

Graft Vessel Wall Pathology in a Case of Hepatic Artery Pseudo-Aneurysm in a Liver Transplant Recipient

Pseudo-aneurysms (PAs) of the hepatic artery are rare complications of liver transplantation, which are characterized by a high mortality rate. The majority occur within the first 2 months after orthotopic liver transplantation. They become clinically manifest with sudden hypotension, gastrointestinal bleeding, and abnormal liver function test results. Early diagnosis and treatment are essential to prevent life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction, but a feasible treatment option involves an angiographic approach with the positioning of a stent or transarterial coil embolization followed by revascularization. We report a case of posttransplantation hepatic artery PA (HA-PA) with bleeding into the duodenum, diagnosed using abdominal computed tomography (CT). Arterial kinking prevented a covered stent graft from being inserted successfully using X-ray angiography, so the patient underwent emergency surgery in an attempt to exclude the PA and revascularize the organ via an aorto-hepatic bypass with an iliac vascular graft obtained from the donor. The surgical procedure failed due to progressive macroscopic dissection of the HA wall up to the bifurcation. The patient underwent retransplantation but died 25 days later due to multiple-organ failure. Histopathology of the first liver graft confirmed arterial graft dissection and pathological changes in the donor HA wall.

HCV796

Anti-hepatitis C virus (HCV) drug development has been challenged by a lack of experience with inhibitors inclusive of in vitro, animal model, and clinical study. This manuscript outlines activity and correlation across such a spectrum of models and into clinical trials with a novel selective nonstructural protein 5B (NS5B) polymerase inhibitor, HCV796. Enzyme assays yielded median inhibitory concentration (IC(50)) values of 0.01 to 0.14 microM for genotype 1, with half maximal effective concentration (EC(50)s) of 5 nM and 9 nM against genotype 1a and 1b replicons. In the chimeric mouse model, a 2.02 +/- 0.55 log reduction in HCV titer was seen with monotherapy, whereas a suboptimal dose of 30 mg/kg three times per day in combination with interferon demonstrated a 2.44 log reduction (P = 0.001 versus interferon alone) Clinical outcomes in combination with pegylated interferon and ribavirin have revealed additive efficacy in treatment naïve patients. Abnormal liver function test results were observed in 8% of HCV-796 patients treated for over 8 weeks, resulting in suspension of further trial activity. The RNA-dependent RNA polymerase inhibitor HCV796 demonstrated potent anti-HCV activity consistently through enzyme inhibition assays, subgenomic replicon, and chimeric mouse studies. Strong correlations of outcomes in the mouse model were seen with subsequent clinical trials, including a plateau in dose-related antiviral activity and additive impact from combination therapy with interferon. These outcomes demonstrate the utility of the range of in vitro and in vivo models now available for anti-HCV drug development and support the potential utility of polymerase inhibitors in future combination therapies for HCV treatment.