Normal Liver Tests Research Articles

Successful Multi-Modality Endoscopic Treatment of Bouveretʼs Syndrome without Surgery

Purpose: An 85-year-old man with dementia and diabetes presented with lethargy, nausea, and coffee-ground emesis. Vital signs were stable and laboratory examination was notable for a leukocytosis, hematocrit of 33%, and normal liver tests. CT scan showed a distended stomach, pneumobilia, and a 3 cm gallstone in close proximity to the duodenum. Endoscopy demonstrated a large gallstone impacted in the duodenal bulb, resulting in gastric outlet obstruction. Given the patient's age and comorbitidies, the patient's surgeon requested endoscopic management. During the course of three endoscopies, the stone was fragmented using a combination of a Holmium:YAG laser and an intracorporeal electrohydraulic lithotripter (IEHL). IEHL was more effective in uniformly shattering the stone's softer outer shell, while the laser was more effective in weakening the stone's internal structure by boring holes into its harder, inner core. The largest fragment was extracted using a double-snare technique, which provided extra grip and leverage. A large cholecystoduodenal fistula was visualized with surrounding ulcerated mucosa, and the gastroscope could be easily advanced into the gallbladder lumen. The patient was discharged to a nursing home, without recurrence of symptoms. Discussion. Gastric outlet obstruction by a gallstone migrating through a cholecystoduodenal fistula (Bouveret's Syndrome) was first described in 1896 and is a rare condition, representing fewer than 5% of cases of gallstone ileus. Patients are often elderly with underlying comorbidities which poses significant challenges to both surgeon and endoscopist. Despite modern surgical techniques, mortality is as high as 30%. Since 1985 there are only a few reports of successful management with endoscopy alone, with more than 90% ultimately requiring surgery. Our experience suggests that endoscopists should initiate stone fragmentation with IEHL as first line management, use laser lithotripsy adjunctively, crush stone fragments that are left in the stomach to prevent migration and ileal obstruction, and prepare for multiple endoscopic sessions. The choledochoduodenal fistula does not require closure. With an aging, obese population, we anticipate Bouveret's to become more common and recommend endoscopists become familiar with the multiple options available for effective endoscopic therapy.

Massive Upper GI Bleed Secondary to Splenic Artery Pseudoaneurysm

Purpose: 22 year old male, history of abdominal trauma, presented with sudden onset of 3 episodes of hematemesis associated with abdominal pain and loss of consciousness. He denied previous episodes of GI bleeding. Two years prior, he had multiple stab wounds to the abdomen and subsequently underwent exploratory laparotomy and ostomy with reversal for perforated bowel. Reports heavy alcohol use on weekends and smokes 1 ppd × 6 years. Upon arrival to the emergency room, vital signs were stable: P73, BP 122/68 with no orthostasis. Abd exam: + BS, NT, ND, + midline and ostomy scars, no organomegaly. Rectal exam: brown stool, guaiac positive. NG lavage was not performed. Labs: WBC 11,900 mm3, Hg 12.5 g/dL, Hct 37.9%, Platelets 323/mm3, BUN/cr ratio19 with normal coagulation profile and liver tests. An EGD was performed. A large fresh clot was seen in the gastric body which could not be suctioned. In addition, fresh blood was seen in the second portion of the duodenum, but no source of bleeding was identified. During endoscopy, the patient had several more episodes of hematemesis and was taken to interventional radiology. A 5 F catheter was placed in the celiac axis and an angiogram was performed. A pseudoaneurysm off the mid splenic artery was identified as the source of bleeding and coils were deployed and packed into the pseudoaneurysm. Repeat angiogram showed no residual flow with good thrombosis. Subsequently, the patient was discharged with no further episodes of GI bleeding and Hct 35%. Few cases have reported GI bleeding in patients where pseudoaneurysms have been thought to spontaneously erode into the GI tract secondary to compression/stress/trauma. Since this patient had sustained prior abdominal trauma in the same anatomical location as the formation of the splenic artery pseudoaneurysm, spontaneous fistularization of the pseudoaneurysm and the gastric wall could have occurred thus explaining his presentation. A thorough review of the literature has reported pseuodocyst and pseudoaneurysm fistularization to arteries supplying the GI tract or to the pancreatic duct in patients with chronic pancreatitis resulting in upper GI bleeding. However, to date, there is no reported case of a pseudoaneurysm of the splenic artery caused as a result of prior abdominal and presenting as trauma hematemesis. Hence, as gastroenterologists, we must be aware of the increasing role of angiographical methods for diagnosing and controlling acute GI bleeding.

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Effect of Roux-en-Y Gastric Bypass (RYGB) on Clinical and Laboratory Data in Morbidly Obese Patients

Purpose: Roux-en-Y Gastric Bypass (RYGB) is the most common and effective procedure performed in the US for surgical treatment of obesity. The likelihood of having non-alcoholic fatty liver disease (NAFLD) is directly proportional to body weight1. NAFLD is being increasingly recognized as a major cause of liver-related morbidity and mortality. Given the increasing prevalence of obesity in North America, NAFLD is an important public health problem. The aim of this study is to determine the incidence of NAFLD in patients who underwent RYGB and to determine the effect of RYGB in a subgroup with abnormal liver tests (which include AST, ALT, alkaline phosphatase and bilirubin). Methods: 400 consecutive patients who underwent RYBP were evaluated retrospectively. Only those who underwent random intra-operative liver biopsy were included. Patients with viral or autoimmune hepatitis, hemochromatosis or alcohol use (>20g/day) were excluded. Pathological analysis recorded the presence and degree of steatosis, portal and lobular inflammation, and ballooning. Preoperative and 6–8 month postoperative clinical and laboratory data was gathered which included age, BMI, AST, ALT, alkaline phosphatase (AP) and bilirubin. Paired t-test was used to compare these variables pre and post operatively. Results: 205 patients were included in the study. 86.3% were female. The mean age was 36.8 ± 10.1 years. The mean BMI was 48.7 ± 7.4 kg/m2. 90.7% had NAFLD as proven by liver biopsy. All the patients with normal liver biopsy had normal liver tests. 25.9% of patients with NAFLD had abnormal liver tests prior to RYGB. Of these patients with abnormal liver tests, 24.5% had abnormal AST, 38.9% had abnormal ALT, 71.7% had abnormal AP and 9.4% had abnormal bilirubin. There was significant improvement of ALT (p= <0.001), AP (p= <0.001) and bilirubin (p= 0.003) after adjusting for the decrease in BMI postoperatively. Conclusions: Our study reiterates that NAFLD is highly prevalent in morbidly obese patients. About one-fourth of morbidly obese patients have abnormal liver tests. Significant improvement of ALT, alkaline phosphatase and bilirubin was noted after bariatric surgery.

Evaluation of Response to Anti-CD20 (Rituximab) Trial in Relapsed Follicular Lymphoma after Six Years in Follow-Up.

Background: Follicular Lymphoma (FL) is characterized by t(14:18)(q32;q21) in 80% patients. Persistence of expression bcl2/JH gene translocation is related to frequent relapses in FL.Purpose: To determine the efficacy of Fludarabine-Mitoxantrone (FLD/MTX) + monoclonal anti CD20 antibody (Rituximab) to induce clinical and molecular response in relapsed FL in base to the presence of bcl-2.Methods: Prospective trial in 31 patients with relapsed FL. An outpatient regimen i.v./28d: FLD 30 mg/m2 1–3 + MTX 10 mg/m2 1 followed by Rituximab (375 mg/m2/weekly x4). Eligibility criteria: adults patients with both (relapsed FL by biopsy + bcl-2 immunohistochemistry expression in nodal biopsy), ECOG<3, normal renal function and liver tests. Exclusion criteria: previous anti-CD20 therapy, chemotherapy within 4 weeks previously, other malignancies, AIDS or other infectious disease. Patients were eligible for registration previous inform consent. Evaluation at baseline included: complete blood counts, serum and urine biochemistry, b2 microglobuline and LDH, body scan, bone marrow (BM) biopsy and PCR-ELISA for t(14;18) in BM. Patients were classified according ECOG, clinical stage and FLIPI. Follow-up monitoring: after FLD/MTX and 2 months after Rituximab, including clinical examination, laboratory, scan, BM examination and t(14;18). Response criteria: Complete remision (CR):resolution tumour mass and BM involvement; partial remission (PR):>75% reduction in tumour mass and BM infiltration <10%. Progression: increase in measurable mass lesion >25% during therapy. Molecular remision (MR): negative PCR-ELISA assay in BM. Statistical analysis: descriptive and frequency distribution, overall survival (OS), relapsed free survival (RFS). Survival curves were estimated using Kaplan-Meier survival analysis.Results: Mar-99 to July03, 31 patients with relapsed FL were enrolled. Mean age: 56.00± 12.44 (range 32–77); M/F: 13/18. ECOG: 0(22), 1(5), 2(2), 3(2). Clinical stage II(4), III(8), IV(19). Previous therapies 1(19), 2(4), and 3 or more(8), FLIPI 0 (3), 1(6), 2(15), 3(7). PCR t(14:18) was positive in BM in 12 cases (40 %). Response: after FLD-MTX, clinical response was obtained in 27 patients, CR 13 (43.3%) and PR 14(46.67%), 2 failed. One not valuable. Rituximab started in 27/28 patients with clinical response (1 refused). After Rituximab: CR 23 (81.4%), PR 4(13.3%) and 2 failures (6.4%) After Rituximab (26 responsive patients): 22 (84.6%) achieved MR, 4 (15.3%) persist PCR-ELISA positive in BM. PBSCT was underwent in 14 CR patients (63.6%). OS: 117 months (range 36–200), median RFS 44,22 months (range 0–73). Relapse was observed in 13(43,3%) and 8 died, only one patient had persistence of t(14;18), mean time to relapse 24.1 m (0–57), 3 patients relapsed after PBSCT. Four patients in CR have died by other causes. Nowadays17 patients remain alive and 12 are in CR.Conclusions: The response to FLD-MTX is obtained in 90 % of patients with relapsed FL, with CR rates 43.3%. The addition of Rituximab does not influence on overall response but improves CR rates (81.4%). The median RFS of group is 117 months only 13 patients developed relapse apparently it is not related to persistence of t(14;18).

Pathology of nonalcoholic steatohepatitis

To date, histologic evaluation, most commonly in the form of liver biopsy, remains the gold standard in evaluation of nonalcoholic fatty liver disease (NAFLD). Histologic evaluation was fundamental to the initial studies that introduced and defined the concept of fatty liver as a liver disease. Currently, liver biopsy in NAFLD serves multiple roles: confirmation (or exclusion) of the diagnosis; distinction of steatohepatitis from "simple steatosis"; assessment of extent of necroinflammatory activity, fibrosis, and architectural alterations. Histopathologic studies have underscored the fact that not all obese and/or diabetic individuals with elevated liver tests have fatty liver disease; for example, hepatic glycogenosis and hepatosclerosis have been described in diabetics, and other significant liver diseases have been documented. Likewise biopsy studies have documented lesions of steatosis or steatohepatitis in unusual patient groups or clinical settings, such as lean individuals, individuals with normal liver tests, patients taking certain medications, patients with co-existent serologically-diagnosed liver disease, and pediatric patients. Biopsy studies have shown that the lesions of NASH may or may not persist in cirrhosis; prior evidence of NASH on liver biopsy serves as a benchmark for the concept that many cases of otherwise cryptogenic cirrhosis developed from NAFLD/NASH. Liver biopsy remains a significant feature of studies delineating long-term outcome of NAFLD, some of which have shown that "simple steatosis" is not always non-progressive and benign. Finally, investigators have noted correlations of proposed pathophysiologic processes in NASH with particular histologic features. Therapeutic trials for NASH rely on histologic evaluation as the most sensitive analysis to document effects of treatment. Treatment trials afford an opportunity to evaluate histologic features of resolution, and these trials have also provided an opportunity for correlations of particular histologic lesions with clinical and laboratory features in well-characterized patient populations. These kinds of studies are currently relatively few, but results of a recent study have reinforced the concept of necessary criteria for diagnosis. Current discussions in pathology include identification of lesions of concern for progression, reproducible methods of diagnosis and semiquantification of lesions, and appropriate nomenclature. Matteoni et al. proposed NAFLD types 1-4 based on long-term outcome studies; Brunt et al. proposed a system of grading and staging for NASH that follows methods of separate assessment for necroinflammatory lesions (grade) and fibrosis (stage) accepted in other forms of non-biliary chronic liver disease. Recently, the Pathology Committee of the NIDDK NASH Clinical Research Network has proposed a system of evaluation that encompasses the entire spectrum of NAFLD from steatosis to steatohepatitis with fibrosis for use in upcoming treatment trials. And, just as the clinician cannot distinguish steatosis and steatohepatitis, the pathologist cannot discern if alcohol abuse may be an underlying cause of the lesions. Proposed nomenclature to align with either extant terminology in other forms of chronic liver disease, or to align with our knowledge of underlying cause(s) (such as metabolic syndrome) will be discussed.

Are genetic polymorphisms of tumour necrosis factor alpha, interleukin-10, CD14 endotoxin receptor or manganese superoxide dismutase associated with alcoholic liver disease?

Four polymorphisms have been described associated with either increased risk for alcoholic liver disease (ALD) or more serious histological lesions: tumour necrosis factor alpha (TNF-alpha) G(-238)A, interleukin-10 (IL-10) C(-627)A, promoter of CD14 endotoxin receptor gene C(-159)T and manganese superoxide dismutase (MnSOD) C(-1183)T/valine --> alanine. We sought confirmatory evidence, through individual and simultaneous analysis of the four aforementioned polymorphisms, in 176 heavy drinkers: ALD (n = 100) if histology-compatible or clinical evidence of hepatic decompensation; and no evidence of liver disease (NLD) (n = 76) if normal liver tests on two occasions or normal liver histology (steatosis alone). Patients with ALD were older (53+/-10 vs. 48+/-10 years, P<0.05), with a similar sex distribution. TNF-alpha G(-238)A showed no difference in heterozygous GA-genotype prevalence (ALD, 9.0%/NLD, 7.9%). IL-10 C(-627)A showed no difference between groups, either homozygote AA (8.0% vs. 10.5%) or heterozygote CA (34.0% vs. 39.5%). CD14 promoter C(-159)T showed no difference between groups in T-allele frequency, either homozygote TT (27% vs. 21%) or heterozygote CT (49% vs. 50%). Alanine MnSOD allele carriers showed no difference between groups in either the heterozygote (55.0% vs. 49.3%) or homozygote (22% vs. 25%). No difference was observed in the probability of having simultaneously two, three or four of the implicated polymorphisms: respectively, 43%, 33% and 0% in ALD, and 43%, 24% and 5% in NLD (not significant). No association was found between the previously implicated polymorphisms of TNF-alpha, IL-10, CD14 and MnSOD, either individually or simultaneously, and the presence of established ALD.

P09.01: Correlations between ultrasound and fetal haematological parameters in 67 fetuses infected with cytomegalovirus (CMV)

To study pronostic factors in fetal blood of fetuses infected by CMV. 69 cases of fetal infections diagnosed by amniocentesis (presence of DNA CMV or positive culture). Prognostic factors that were evaluated against ultrasound (US) and MRI of the fetal brain included: Haematological parameters: presence of CMV DNA, trend in fetal blood viral load, platelet count, biochemical markers including Gamma Glutamyl transferase (GGT) and liver enzymes. When termination of pregnancy (TOP) was performed, all fetuses were examined to assess the severity of fetal infection. Follow up of infected neonates was up to 96 months. Good outcome (GO) was achieved in 30 cases (42%), poor outcome (PO) in 39 cases (58%), including 33 TOP, 2 intra uterine fetal deaths, 1 unilateral deafness, 3 mental retardations caused by severe brain anomaly. US parameters were normal in 30 cases (44%), abnormal in 37 (66%). Good outcome was observed in 23 cases/30 without abnormal US signs, although in 5 cases presence of abnormal biological parameters led toTOP. Autopsy confirmed severe disseminated infection. Sensitivity (Sens) of abnormal US parameters to predict a poor fetal outcome was 82%, with positive predictive value (PPV) of 86% and specificity (Spec) of 82%. Sens of abnormal biological parameters to predict a poor fetal outcome was 94% with PPV of 94.8%. In case of absent abnormal ultrasonographic signs, or minor signs, Sens of normal biological parameters was 91%, PPV 95%, Spec 85%. The most effective biological tests useful for appropriate evaluation of fetal prognosis was the platelet count (98% of normal results in case of GO versus 38% in case of PO, p < 0.001), followed by normal fetal liver tests (88% of normal liver tests in case of GO, versus 30% in PO, p < 0.01). A combination of ultrasonographic and biological parameters allows to identify more accurately than ultrasound alone the fetuses with good or adverse outcome.

Ursodeoxycholic acid treatment in isolated chronic graft‐vs.‐host disease of the liver

Data regarding the long-term treatment of ursodeoxycholic acid (UDCA) in individuals of chronic graft-vs.-host disease (cGVHD) of the liver are limited. The aims of this prospective study were to determine whether, (i) UDCA treatment is useful as a long-term treatment for individuals with limited cGVHD of the liver following allogeneic hematopoietic cell transplantation, and (ii) the tolerability of UDCA treatment in such individuals. Fifteen consecutive patients with de novo isolated cGVHD of the liver were included. All individuals were treated with UDCA at a dose of 13 mg/kg/d for 1 yr. Clinical evaluation and laboratory testing were assessed at 30-d intervals during UDCA therapy and every 30 d after discontinuation of UDCA for a total of 3 months. At the end of the treatment, 60% of patients with cGVHD of the liver had normal liver tests, the remaining 40% of patients demonstrated improvement in their abnormal liver tests (partial responders), whereas none of the patients had worsening of the liver tests. When compared with baseline, there was a significant decrease in the serum aminotransferases, alkaline phosphatase and gamma-glutamyl transpeptidase levels after completion of the UDCA treatment at 12 months (p < 0.01). No significant increase in serum liver enzyme tests was observed at the third month after the completion of therapy. Pruritus in seven of nine patients resolved after UDCA treatment. All patients completed their assigned treatment with no major adverse event. Long-term UDCA therapy appears to be effective, safe and tolerable in individuals with cGVHD presenting with isolated liver involvement.

Role of EUS for Evaluating Bile Duct Dilation in Patients with Normal Liver Tests and Normal CT/MRU

Role of EUS for Evaluating Bile Duct Dilation in Patients with Normal Liver Tests and Normal CT/MRU Mark S. Lemert, Robert Lin, Gordon Hunt, Mary Lee Krinsky, Thomas Savides Background: Due to widespread use of noninvasive imaging studies, patients are frequently encountered with findings of common bile duct (CBD) dilation without evidence of pancreatic/ampullary mass or CBD stones on CT/MRI. The aim of this study was to compare the diagnostic yield of EUS for CBD dilation in patients with a history of normal versus elevated liver function tests (LFTs). Methods: Retrospective review of patients who were referred for EUS evaluation of CBD dilation from January 2001 to November 2004. The inclusion criteria were evidence of CBD dilation (O7 mm) without obvious obstructing mass lesion or CBD stone by preliminary imaging [transabdominal U/S, CT scan, and/or MRI/MRCP]. A comparison of EUS findings in patients with normal and elevated LFTs was conducted. Among patients without malignancy or choledocholithiasis, a comparison of CBD diameter, based on a clinical cut score of 7 mm was conducted across four groups with regard to the following risk factors: age O 60 and/or a history of cholecystectomy (CCY). Results: 127 patients met the inclusion criteria. The mean age was 63 (range 22-93), 76% were female, 67% reported symptoms of abdominal pain, and 43% were status-post CCY. 11% had normal bile duct diameters on EUS. Of 74 patients with normal LFTs, 4 cases (5%) of choledocholithiasis were diagnosed. Of 53 patients with a history of elevated liver tests, either stones or cancer was diagnosed in 30 (57%), with choledocholithiasis in 20 (34%), pancreatic cancer in 6 (11%), and ampullary cancer in 5 (9%). This difference in EUS findings between normal versus abnormal LFTs was significant when analyzed using the chisquare statistic (XZ41.29, pZ0.00). Examination of EUS determined CBD diameter in patients without pathology findings on EUS demonstrated that those patients with R1 risk factors for CBD dilation had significantly increased likelihood of CBD diameter exceeding the clinical cut-off of 7 mm (X Z 12.16, pZ.007). Conclusion: Patients who are referred for EUS to evaluate a dilated CBD, but have no lesion on CT/MRI and have normal liver tests are significantly less likely to have any pathology (5% chance of stones), compared to similar patients with elevated liver tests (57% chance of stones or tumors). Implications: Patients who are found by body imaging studies to have a dilated bile duct, but have a normal CT/MRI and normal LFTs may not need further diagnostic testing.

HEMOPHAGOCYTIC SYNDROME

A 29 year old male with ulcerative colitis presented with fatigue, fevers, diarrhea, nausea and a rash. He had pan-ulcerative colitis refractory to 5-ASA agents requiring the intermittent use of steroids. Nine months prior to presentation he began 6-mercaptopurine (6-MP) and tapered prednisone to 5 mg qd. He tolerated 6-MP well with persistently normal complete blood counts and liver tests. He otherwise had no significant past medical history and was on no other medications. On examination, he appeared fatigued but non-toxic, with a temperature of 39.1 C, heart rate 106 and blood pressure 104/64. There was a confluent erythematous rash over his forehead, face and shoulders. The remainder of the physical exam was unremarkable. Laboratory evaluation was significant for a white blood cell count of 1700 with 68% band forms, hemoglobin of 12.0 g/dL and platelets of 40,000. He had an elevated aspartate aminotransferase of 181 U/L and alanine aminotransferase of 205U/L. He was admitted to the hospital with presumed 6-MP toxicity and a superimposed viral infection. He continued to spike fevers and developed profound pancytopenia with an absolute neutrophil count of 420, hemoglobin of 8.7 g/dL and platelets of 8,000. Blood cultures and viral studies were negative including parvovirus, CMV, HIV, HSV, hepatitis A, B, C and a monospot. However, Epstein-Barr Virus (EBV) Ig M, EBV IgG and EBV nuclear antigen were all positive. A bone marrow biopsy showed infiltration with CD68 positive macrophages filled with phagocytosed hematopoietic cells diagnostic of hemophagocytic syndrome. Despite treatment with IVIg, etoposide and dexamethasone, he decompensated and was intubated for respiratory failure. On hospital day 15 he died. A post-mortem examination confirmed extensive infiltration of atypical macrophages in multiple organs consistent with hemophagocytic syndrome. Hemophagocytic lymphohistiocytosis is a rare syndrome that involves the accumulation and infiltration of activated T-cells and macrophages. The familial form usually affects young children, while the acquired form is associated with infections, most frequently EBV There are rare reports of this syndrome in patients with inflammatory bowel disease. This case raises concern that hemophagocytic syndrome is a life-threatening complication of ulcerative colitis and/or immunomodulator therapy.

Treatment of murine hepatocellular carcinoma using genetically modified cells to express interleukin-12.

The majority of patients cannot benefit from the conventional curative treatments that are currently used for hepatocellular carcinoma (HCC), which remains a world health problem. Interleukin (IL)-12 is one of the most potent anti-tumor cytokines. The aim of the present study was to examine the anti-tumor effect and toxicity of intrahepatic delivery of IL-12 using an ex vivo gene therapy approach in a murine model of HCC. Syngenic fibroblasts or MM45T-Li HCC tumor cells were genetically modified in vitro to express IL-12 using a polycistronic TFG murine IL-12 retroviral vector (TFGmIL-12) coding for both p35 and p40 murine IL-12 subunits. Hepatocellular carcinoma was generated using direct intrahepatic inoculation of the tumor cell line into the left liver lobe of BALB/c mice. Direct liver expression of IL-12 by the injected genetically modified tumor cells induced a marked inhibition of tumor growth. This effect was associated with an early infiltration of macrophages, and lymphocytes forming numerous intralobular foci. There was no significant liver toxicity, as shown by normal biochemical liver tests. At a later time, the intralobular foci were rare and consisted mainly of CD4+ T cells, while CD8+ T cells were present in the lobule. Intrahepatic expression of IL-12 did not modify circulating or splenic B lymphocytes or natural killer (NK) cells. The inhibition of tumor growth was maintained in nude mice even when depleted in NK cells. Importantly, in a second model, treatment of established day 7 liver tumors in BALB/c mice using direct intra-tumor injection of syngenic fibroblasts that were genetically modified to express IL-12 significantly reduced tumor size. In conclusion, these data provide evidence that experimental HCC can be efficiently and safely treated using ex vivo IL-12 gene therapy, which seems promising for future clinical studies.

Evaluation of the donor liver for living donor liver transplantation.

Key points 1. Accurate assessment of the donor liver is an important component of the living donor liver evaluation and is critical to ensure a successful outcome for both donor and recipient. 2. Liver biochemistry tests, viral hepatitis serological tests, tests to exclude chronic liver disease, and volumetric computed tomographic or magnetic resonance (MR) imaging of the liver are performed routinely as part of the donor evaluation. 3. Liver biopsy should be a standard component of the donor evaluation in all donors, with the possible exception of those with a body mass index less than 25 who have normal liver test and abdominal imaging study results and no risk factors for chronic liver disease or hepatic steatosis. 4. The maximum acceptable percentage of steatosis in the donor liver is unknown, but most centers use an upper limit of 10% to 30%. 5. A graft-recipient body weight ratio of at least 0.8% provides the recipient with adequate hepatic mass in most situations. 6. Anatomic variants in donor biliary and hepatic vascular anatomy are common. 7. Evaluation of donor vascular anatomy varies among centers and includes MR or computed tomographic angiography and hepatic angiography. 8. Evaluation of biliary anatomy is performed most commonly using intraoperative cholangiography. Some centers use MR cholangiography or endoscopic retrograde cholangiopancreatography in selected situations.

Pegylated interferon for recurrent hepatitis C in liver transplant recipients with renal failure: a prospective cohort study

BackgroundHepatitis C (HCV) universally recurs following orthotopic liver transplantation (OLT), representing an important cause for retransplantation. Although it is often treated with interferon and ribavirin, ribavirin is contraindicated in the presence of renal failure. In this setting of renal failure, pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients. MethodsBetween June 2001 and November 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment, end of treatment (EOT) and 6 months after EOT for those who were HCV-RNA negative at EOT. Patients were followed prospectively after starting weekly pegylated-interferon alpha 2b 1.0 μg/kg (Schering-Plough, Kenilworth, NJ, USA). ResultsAmong the 45 patients with recurrent HCV screened, 9 were eligible, including 8 men and 1 woman of average age 55 years. Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months. Two patients developed a sustained response to HCV eradication. One patient who completed treatment has normal liver tests but is still viremic. ConclusionPegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure. Larger, prospective studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life.

Epirubicin in patients with liver dysfunction: development and evaluation of a novel dose modification scheme

This study aimed to develop an epirubicin dose modification scheme in women with breast cancer and liver dysfunction. We first identified target areas under the concentration-time curve (AUCs) of 2400 and 1600 ng/ml.h from pharmacokinetic studies in 15 women with normal liver tests. In a second group of 16 women with abnormal liver biochemistry, the relationship between raised asparate aminotransferase (AST) and epirubicin clearance was: dose=AUC (97.5−34.2×log AST). Adaptive dosing was evaluated prospectively in a third group of 41 women with serum AST ⩾2×normal±raised bilirubin. The median AUCs were 2444 and 1608 ng/ml.h, close to the high and low target AUCs, respectively. Variability in AUC was lower with adaptive dosing than in a fourth group given an unadjusted dose of epirubicin (coefficient of variation=25.8, 30.0 and 46.5%, respectively; P=0.06). Epirubicin dosing based on AST is safe and may reduce pharmacokinetic variability.

Serum alpha-glutathione S-transferase as a sensitive marker of hepatocellular damage in patients with cystic fibrosis

The aim of the study was to evaluate serum a-glutathione S-transferase (s-GSTA) levels in patients with cystic fibrosis (CF) and to compare s-GSTA with other liver function tests and with a hepatic ultrasound scan (US). The cytosolic enzyme, a-glutathione S-transferase is predominantly found in the liver and is distributed uniformly in the liver tissue. In our study s-GSTA levels were measured in 37 CF patients aged 1 to 28 years (mean age 10.4 years, 24 males). The control group consisted of 27 patients aged 2 to 17 years (mean age 8.5 years, 18 males). The presence of hepatobiliary abnormalities was assessed by clinical examination, ultrasound scan, s-GSTA, and conventional liver enzymes: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and g-glutamyl transferase (GMT). The calculated 5-95 % range of s-GSTA for the control group was 0.098-2.54 mg/l, for the CF group 0.43-9.76 mg/l. Mean s-GSTA level in the control group was 1.55 mg/l (S.D.=1.57), and 2.05 mg/l (S.D.=2.60) in the CF group. In the group of CF patients, the serum levels were significantly higher than in the control group (P&lt;0.01). No significant correlation existed in the CF group between s-GSTA and conventional liver tests (ALT, AST, ALP and GMT). Four patients in the CF group had hepatobiliary abnormalities detectable by conventional liver tests, s-GSTA and US. Four patients had abnormal s-GSTA, while conventional liver tests and US were normal. One other patient had abnormal hepatic US, but normal standard liver tests and s-GSTA. The study has suggested that a raised s-GSTA level might be a marker of possible pathological changes of the hepatobiliar system in CF patients. Serum GSTA seems to be a more sensitive marker than transaminases for the monitoring of hepatocellular integrity and as an early predictor of hepatic damage.

Prevalence of hepatitis C infection in a large urban hospital-based sample of individuals with spinal cord injury

Fong T-L, Adkins RG, Govindarajan S, Post S, Waters RL. Prevalence of hepatitis C infection in a large urban hospital-based sample of individuals with spinal cord injury. Arch Med Rehabil 2002;83:1620-3. Objective: To examine the prevalence and clinical characteristics of hepatitis C infection in individuals with chronic spinal cord injury (SCI). Design: Retrospective case survey. Setting: Outpatient clinic devoted to SCI follow-up care located in a county-government rehabilitation center. Participants: A total of 531 unselected individuals with chronic SCI. Interventions: Patients underwent routine annual physical examinations at the outpatient clinic, and were tested for hepatitis C antibodies, antibodies to hepatitis core antigen, alanine aminotransferase (ALT), and bilirubin. Main Outcome Measures: Prevalence of hepatitis C antibodies and liver test abnormalities. Results: Seventeen percent of the cohort was anti-hepatitis C virus (HCV) reactive (HCV positive). The prevalence of HCV infection in those who sustained SCI before 1990 was 21% compared with 7% (10/147) of those who were injured from 1990 onward (X2/1=13.9, P=.0002). Period of injury (WaldX2/1=8.2, P=.0042) and age (WaldX2/1=3.9, P=.048) were the only significant factors for anti-HCV reactivity. Thirty percent of the HCV-positive individuals had abnormal ALT levels compared with only 10% of the HCV-negative individuals (X2/1=25.0, P<.0001). Individuals who were HCV positive were more likely to be hepatitis B core antigen-reactive compared with those who were HCV negative (31% vs 9%;X2/1=34.1, P<.0001). Conclusions: The prevalence of HCV infection among individuals with chronic SCI is significantly higher than the general population. The majority of those with SCI and HCV infection have normal liver tests. Clinicians should maintain a high index of suspicion for HCV infection, even in the absence of elevated aminotransferase activities. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Results of long-term ursodiol treatment for patients with primary biliary cirrhosis

OBJECTIVE: When ursodeoxycholic acid (UDCA) is used for the treatment of primary biliary cirrhosis, it has been associated with biochemical improvement, histological stability, reduced risk of esophageal varices, and increased survival free of transplantation. There is limited information available about the long-term outcome of these patients with primary biliary cirrhosis on UDCA treatment. To address this, we reviewed the long-term results from patients enrolled in our original randomized study with up to 12 yr of follow-up. METHODS: From April 1988 to March 1992, a total of 180 patients were enrolled into a randomized, controlled trial evaluating UDCA (n = 89) versus placebo (n = 91). When the randomized portion of the study concluded in May 1992, patients were switched to active medication and followed for up to an additional 8 yr. RESULTS: Twenty-eight patients originally assigned to UDCA and 42 patients originally assigned to placebo have died or undergone transplantation. The patients who died or were transplanted were more histologically advanced at entry ( p < 0.001). Seventy-six of the remaining 110 patients return for regular follow-up; mailed questionnaires were returned by an additional 25 patients, and nine patients have been lost to follow-up. Twenty-two of the 76 patients we follow have normal liver tests (ALP, bilirubin, and AST). Patients with normal liver tests had significantly lower levels of ALP and AST at baseline ( p < 0.05), but did not differ in histological stage or total bilirubin from those with persistently abnormal tests. CONCLUSIONS: UDCA appears to be of most benefit when instituted in early stage disease. Although a substantial percentage of patients will achieve biochemical normalization on UDCA alone, there is a continued need for therapeutic options for others who have less complete biochemical responses.

Anti‐CD20 Monoclonal Antibody (Rituximab) Treatment for Epstein‐Barr Virus‐associated, B‐cell Lymphoproliferative Disease in Pediatric Liver Transplant Recipients

ABSTRACTObjectivesAnti–B‐cell immunotherapy has been used with success in adults with posttransplant B‐cell lymphoproliferative disease (PTLD), but such treatment has rarely been reported in children. We report the outcome of anti–CD20 antibody (rituximab) therapy for Epstein‐Barr virus (EBV)–associated PTLD in six pediatric liver transplant recipients.MethodsIn these six patients, PTLD was diagnosed within 2 to 4 months after transplantation. The tumors were classified as monomorphic or polymorphic B‐cell infiltrate expressing CD20 antigen and EBV genome. Anti‐CD20 therapy was associated with withdrawal of tacrolimus or ciclosporine therapy in all patients. Intravenous rituximab was administered at 375 mg/m2 once a week for 3 to 4 consecutive weeks.ResultsRituximab treatment was associated with decreased EBV load, disappearance of abnormal serum immunoglobulin concentration, and disappearance of tumoral masses, which occurred 1 to 2.5 months after treatment onset. Despite rituximab therapy, one patient was diagnosed subsequently with a cerebral tumor. Five patients experienced acute liver graft rejection episodes within 10 days to 2.5 months after beginning treatment. In these patients, immunosuppression was reintroduced, but three children experienced fatal chronic rejection, whereas two experienced complete tumor remission. Three children are alive and in complete remission, with normal liver tests, 15 months to 3 years after PTLD onset.ConclusionsRituximab therapy is an interesting approach for children with early EBV‐associated PTLD after liver transplantation. It does not prevent cerebral localization, and rapid resumption of immunosuppression may be advisable to prevent lethal chronic liver graft rejection.

Anti-CD20 monoclonal antibody (Rituximab) treatment for Epstein-Barr virus-associated, B-cell lymphoproliferative disease in pediatric liver transplant recipients.

Anti-B-cell immunotherapy has been used with success in adults with posttransplant B-cell lymphoproliferative disease (PTLD), but such treatment has rarely been reported in children. We report the outcome of anti-CD20 antibody (rituximab) therapy for Epstein-Barr virus (EBV)-associated PTLD in six pediatric liver transplant recipients. In these six patients, PTLD was diagnosed within 2 to 4 months after transplantation. The tumors were classified as monomorphic or polymorphic B-cell infiltrate expressing CD20 antigen and EBV genome. Anti-CD20 therapy was associated with withdrawal of tacrolimus or ciclosporine therapy in all patients. Intravenous rituximab was administered at 375 mg/m2 once a week for 3 to 4 consecutive weeks. Rituximab treatment was associated with decreased EBV load, disappearance of abnormal serum immunoglobulin concentration, and disappearance of tumoral masses, which occurred 1 to 2.5 months after treatment onset. Despite rituximab therapy, one patient was diagnosed subsequently with a cerebral tumor. Five patients experienced acute liver graft rejection episodes within 10 days to 2.5 months after beginning treatment. In these patients, immunosuppression was reintroduced, but three children experienced fatal chronic rejection, whereas two experienced complete tumor remission. Three children are alive and in complete remission, with normal liver tests, 15 months to 3 years after PTLD onset. Rituximab therapy is an interesting approach for children with early EBV-associated PTLD after liver transplantation. It does not prevent cerebral localization, and rapid resumption of immunosuppression may be advisable to prevent lethal chronic liver graft rejection.