bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic sinusoidal vasodilators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver
Authors: Slehria Sanjeev , Rajvanshi Pankaj , Ito Yoshiya , Sokhi Rana P. , Bhargava Kuldeep K. , Palestro Christopher J. , McCuskey Robert S. , Gupta Sanjeev
Published: March 2004

After transplantation, hepatocytes entering liver sinusoids are engrafted, whereas cells entrapped in portal spaces are cleared. We studied whether hepatic sinusoidal dilatation will increase the entry of transplanted cells in the liver lobule, improve cell engraftment, and decrease microcirculatory perturbations. F344 rat hepatocytes were transplanted intrasplenically into syngeneic dipeptidyl peptidase IV (DPPIV)-deficient rats. Animals were treated with adrenergic receptor blockers (phentolamine, labetalol), a calcium channel blocker (nifedipine), and splanchnic vasodilators (nitroglycerine, calcitonin gene-related peptide [CGRP], glucagon). Transplanted cells were localized by histochemistry. The hepatic microcirculation was studied with in vivo videomicroscopy. Changes in cell translocations were analyzed by injection of 99mTc-labeled hepatocytes. Pretreatment with phentolamine and nitroglycerine increased transplanted cell entry in liver sinusoids, whereas labetalol, nifedipine, CGRP, and glucagon were ineffective. Increased deposition of transplanted cells in sinusoids resulted in greater cell engraftment. In vivo microscopy showed disruption of sinusoidal blood flow immediately after cell transplantation with circulatory restoration requiring more than 12 to 24 hours after cell transplantation. However, in nitroglycerine-treated animals, sinusoidal blood flow was perturbed less. Nitroglycerine did not meaningfully increase intrapulmonary cell translocations. In conclusion, these findings indicate that hepatic sinusoidal capacitance is regulated by α-adrenergic- and nitroglycerine-responsive elements. Sinusoidal vasodilatation benefited intrahepatic distribution of transplanted cells and restored hepatic microcirculation after cell transplantation. This shall facilitate optimization of clinical cell transplantation and offers novel ways to investigate vascular mechanisms regulating hepatic sinusoidal reactivity.
Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis
Authors: Ratziu Vlad , Bonyhay Luminita , Di Martino Vincent , Charlotte Frederic , Cavallaro Lucas , Sayegh-Tainturier Marie-Hélène , Giral Philippe , Grimaldi André , Opolon Pierre , Poynard Thierry
Published: March 2004

Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, age- and sex-matched C-HCV controls (P < .02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.
Stimulation of α2-adrenergic receptor inhibits cholangiocarcinoma growth through modulation of Raf-1 and B-Raf activities
Authors: Kanno Noriatsu , LeSage Gene , Phinizy Jo Lynne , Glaser Shannon , Francis Heather , Alpini Gianfranco
Published: March 2004

Growth factor signaling, mediated by the mitogen-activated protein kinase (MAPK) cascade, induces cell mitosis. Adenosine 3',5'-monophosphate (cAMP) may inhibit or stimulate mitosis (depending on the cell type) through the activation of MAPK and Raf proteins. Among Raf proteins, Raf-1 and B-Raf differentially regulate mitosis. Our aims were to evaluate the role and mechanisms of action of the α2-adrenergic agonist UK14,304 in the regulation of growth of the human cholangiocarcinoma cell line Mz-ChA-1. Immunocytochemistry and immunoblotting for α2A-, α2B-, or α2C-adrenergic receptor subtypes showed positive reaction in Mz-ChA-1 cells. We found that physiological concentrations of UK14,304 increased cAMP levels and inhibited proliferation and MAPK activity in Mz-ChA-1 cells. Mz-ChA-1 cells expressed Raf-1 and B-Raf. Epidermal growth factor (EGF) immediately and transiently stimulated Raf-1 activity, whereas B-Raf activity was increased with prolonged EGF stimulation. EGF-stimulated Raf-1 and B-Raf activities were both inhibited by UK14,304. UK14,304 did not affect Ras activity. In Mz-ChA-1 cells, α2-adrenoreceptor stimulation causes up-regulation of cAMP, which inhibits EGF-induced MAPK activity through an acute increase of Raf-1 and sustained activation of B-Raf. In conclusion, because α2-AR inhibition of growth occurred downstream of Ras, adrenergic stimulation or other stimulants of cAMP may overcome the Ras mutations and offer a new therapeutic approach for patients with cholangiocarcinoma.
Prevalence of gallbladder disease in American Indian populations: Findings from the Strong Heart Study
Authors: Everhart James E. , Yeh Fawn , Lee Elisa T. , Hill Michael C. , Fabsitz Richard , Howard Barbara V. , Welty Thomas K.
Published: March 2004

American Indians are believed to be at high risk of gallbladder disease (GBD), but there has been no systematic evaluation of its prevalence among diverse groups of American Indians. Therefore, we determined the prevalence of GBD and associated risk factors among specified American Indian populations using ultrasonography of the gallbladder and standardized diagnostic criteria. Enrolled members, aged 47 years and older, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota who participated in the Strong Heart Study were analyzed. GBD was the sum of gallstones (determined by ultrasound examination) and cholecystectomy (determined by ultrasound and self-report). The proportion of American Indian heritage was based on the heritage of the grandparents of participants. GBD prevalence was determined among 3,296 participants at the 3 sites. Among women, 17.8% had gallstones, and 46.3% had evidence of a cholecystectomy, for a total of 64.1% with GBD. Among men, 17.4% had gallstones, and 12.1% had evidence of a cholecystectomy, for a total of 29.5% with GBD. When figures were adjusted for age and Indian heritage, there was no significant difference in GBD prevalence across the 3 geographical areas. In multivariate logistic regression analysis, age, American Indian heritage, and waist circumference were associated with GBD among men, and age, American Indian heritage, diabetes, and parity were associated with GBD among women. Body mass index was not independently associated with GBD in either sex. In conclusion, GBD was found in epidemic proportions in diverse American Indian populations.
Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B
Authors: Hsu Yao-Shih , Chien Rong-Nan , Yeh Chau-Ting , Sheen I-Shyan , Chiou Hung-Yi , Chu Chia-Ming , Liaw Yun-Fan
Published: March 2004

During the course of chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion to its antibody (anti-HBe) often coincides with normalization of liver biochemical test and clinical remission, but data regarding long-term outcome after spontaneous seroconversion are still scarce. Excluding patients with other virus(es) concurrent infection, 283 patients with chronic HBV infection were followed up for at least 1 year after spontaneous HBeAg seroconversion to anti-HBe. Follow-up studies included clinical, biochemical, and virologic evaluation and hepatocellular carcinoma (HCC) screening with ultrasonography and α-fetoprotein assay. During a median follow-up period of 8.6 years (range, 1 to 18.4 years) after HBeAg seroconversion in 283 patients, 189 (66.8%) showed sustained remission, whereas the remaining 94 (33.2%) experienced alanine aminotransferase (ALT) elevation over twice the upper limit of normal: 12 (4.2%) associated with HBeAg reversion, 68 (24%) with detectable serum HBV DNA but HBeAg negative, and 14 (4.9%) of undetermined causes. Of the 269 patients without evidence of cirrhosis at the time of HBeAg seroconversion, 21 (7.8%) developed cirrhosis with a cumulative incidence and relative risk significantly higher in patients developing active hepatitis than in patients with sustained remission (P < .05). HCC developed in 6 (2.2%) of the 283 patients, also with a significantly higher cumulative incidence in patients developing active hepatitis after HBeAg seroconversion (P < .005). In conclusion, the results suggest that spontaneous HBeAg seroconversion confers favorable long-term outcomes. However, active hepatitis still may develop and lead to cirrhosis and HCC.
Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease
Authors: Steinmüller Thomas , Seehofer Daniel , Rayes Nada , Müller Andrea R. , Settmacher Utz , Jonas Sven , Neuhaus Ruth , Berg Thomas , Hopf Uwe , Neuhaus Peter
Published: March 2004

Liver transplantation in patients with hepatitis B has been under discussion for 20 years because of inferior results without reinfection prophylaxis; therefore, we analyzed our overall experience with liver transplantation in hepatitis B patients with immunoprophylaxis, particularly the influence of the available antiviral treatment in different periods. From 1988 to 2000, 228 liver transplants in 206 hepatitis B patients were performed. Indications were acute liver failure (10%), hepatitis B virus (HBV) cirrhosis alone (67%) or with hepatitis D virus (HDV) (13%), or hepatitis C virus (HCV) coinfection (7%). All patients received long-term immunoprophylaxis (anti-HBs > 100 U/L). HBV DNA-positive patients were treated before and after surgery with famciclovir or lamivudine since 1993 and 1996, respectively. Since 1993, antivirals also were used for HBV reinfection. The 1-, 5-, and 10-year patient survival rates were 91%, 81%, and 73%. In patients with hepatocellular carcinoma (HCC) (60% 5-year survival, P < .01) or HBV reinfection (69% 5-year survival, P < .01) survival was significantly impaired. Those with HDV or HCV coinfection had a slightly better survival than with HBV monoinfection (P > .05, not significant). Preoperative positive HBV DNA (hybridization-assay) test results were associated with a slightly impaired patient survival (78% 5-year survival, P > .05, not significant versus DNA-negative). Preoperative positive hepatitis B e antigen (HBeAg) predicted significantly worse survival (P < .05 versus negative HBeAg). Graft loss caused by reinfection was most frequent before the availability of antiviral drugs. Two-year patient survival increased from 85% in era I (1988-1993) to 94% in era III (1997-2000, P < .05). The 2-year recurrence rates in these 2 periods were 42% and 8% (P < .05). In conclusion, excellent long-term results can be achieved in hepatitis B patients after liver transplantation with modern strategies, and survival rates are similar to other indications. Based on our experience, hepatitis B patients, including those with active viral replication, should not be excluded from liver transplantation.
Acute rejection of hepatic allografts from HLA-DR13 (Allele DRB1*1301)-positive donors
Authors: Oertel Michael , Berr Frieder , Schröder Sabine , Schwarz Rene , Tannapfel Andrea , Wenzke Michael , Lamesch Peter , Hauss Johann , Kohlhaw Kay
Published: March 2004

Acute rejection of hepatic allografts does not show consistent association with the number of mismatches of HLA classes I and II. Therefore, we investigated the relation between specific donor or recipient HLA antigens and the occurrence of acute rejection. HLA typing of 35 liver transplant recipients and donors was performed by serological standard technique, with confirmation and subtyping by polymerase chain reaction with sequence-specific primers. HLA class I antigens were not associated with the occurrence of acute rejection. The graft was positive for HLA-DR13 in 8 of 13 transplant recipients (62%) with acute rejection, but only 4 of 22 recipients (18%;P = .024; P
Bonferroni-corrected = .33, not significant) without rejection. The graft was positive for DRB1*1301 in 7 of 13 recipients (54%) with acute rejection, but only 1 of 22 recipients (5%) without rejection (P = .002; P
Bonferroni-corrected= .028). This patient had experienced long-lasting bacterial sepsis, which markedly reduced the risk for acute rejection. We speculate that the expression of donor DRB1*1301 (if mismatched) may increase the risk for acute hepatic allograft rejection.
Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudine
Authors: Sponseller Craig A. , Bacon Bruce R. , Di Bisceglie Adrian M.
Published: March 2004

Lamivudine is effective in inhibiting hepatitis B virus (HBV) replication, and its clinical use in patients with chronic hepatitis B is associated with improvements in serum aminotransferase levels and liver histopathologic characteristics. Few data are available on its use in patients with advanced liver disease. We report on the outcomes of 5 patients with hepatic decompensation caused by chronic hepatitis B treated long term with lamivudine. All patients were adult white men seropositive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) before therapy. All 5 patients had biopsy-proven cirrhosis with clinical and biochemical evidence of hepatic decompensation. Two patients had Child’s class C cirrhosis; 2 patients, class B; and 1 patient, class A (although this patient had persistent portasystemic encephalopathy and developed variceal bleeding). HBV DNA became undetectable in all patients and remained so throughout the study. Both patients with Child’s class C and 1 patient with class B cirrhosis had significant clinical improvement. Child-Pugh scores improved from 12 to 7 and 11 to 7 in the 2 patients with Child’s class C cirrhosis, and the patient with class B cirrhosis had complete resolution of troublesome encephalopathy. Serum aminotransferase, albumin, and total bilirubin levels improved significantly in 3 of 5 patients. One patient with Child’s class B cirrhosis underwent orthotopic liver transplantation at week 13 after dramatic increases in liver tests and clinical worsening. The patient subsequently cleared HBeAg and HBsAg from serum posttransplantation. In conclusion, prolonged therapy with lamivudine resulted in improved serum biochemical values and loss of HBV DNA in patients with decompensated cirrhosis. Clinical improvements, reflected in Child-Pugh classification and functional status, may also occur, particularly among those with Child’s class C disease initially.
Long-term complications of living donor liver transplantation
Authors: Renz John F. , Roberts John P.
Published: March 2004

Key Points

1. Donor outcome after living donor liver transplantation (LDLT) is related to type of liver resection. Left lateral segmentectomy is used in pediatric cases and right lobectomy is used in adult cases.

2. Biliary complications occur in 5% to 10% of both pediatric and adult cases.

3. Three donors, 2 in pediatric LDLT and 1 in adult LDLT, have died. Estimated mortality is 0.13% for pediatric donation and 0.2% for adult donation.

4. Postoperative cholestasis occurs commonly in donors, but clinically relevant jaundice occurs in less than 5%.

5. Other donor morbidity may be related to incisional hernias, postoperative gastric dysfunction, and pain.

6. Donors report overall satisfaction with LDLT, and 88% believed that the role of LDLT should be increased.

7. All donors returned to predonation activities; 25% by 1 month, 75% by 3 months, 88% by 6 months, and 100% by 1 year.
Early detection and treatment of cholangiocarcinoma
Authors: Gores Gregory J.
Published: March 2004

Key Points

1. The major identified risk factor for the development of cholangiocarcinoma in Western countries is primary sclerosing cholangitis (PSC).

2. The diagnosis of cholangiocarcinoma in PSC requires a high index of suspicion because endoscopic brush cytology and/or biopsies and imaging studies are often negative for malignancy. Positron emission tomography is a promising imaging modality for the diagnosis of cholangiocarcinoma, even in patients with PSC.

3. A serum carbohydrate antigen 19-9 value greater than 100 U/mL has a sensitivity and specificity for cholangiocarcinoma of approximately 75% and 80%, respectively.

4. Liver transplantation is a viable therapeutic option for selected patients with early-stage cholangiocarcinoma. Outcomes are optimized by using preoperative radiation and chemotherapy and ensuring the absence of metastases by an exploratory laparotomy.
Posttransplantation prevention and treatment of recurrent hepatitis C
Authors: Burroughs Andrew K.
Published: March 2004

Key Points

1. Hepatitic C virus (HCV) viremia is universal after orthotopic liver transplantation (OLT) for HCV cirrhosis.

2. At 5 years post-OLT, approximately 20% of patients have cirrhosis caused by recurrent hepatitis C.

3. Progression of disease is related to immunosuppression, immune response (CD4+ lymphocytes), HCV genotype, and HCV quasispecies homogeneity.

4. Whether a therapeutic strategy of pre-OLT or early (preemptive) antiviral therapy is better than treating a clinically important hepatitis and the duration of treatment are not known.

5. Monotherapy with recombinant interferon-α or ribavirin is not useful in the long term.

6. Combination therapy (interferon and ribavirin) has given better results, but long-term data are not available.

7. HCV recurrence will benefit from randomized studies.
Pregnancy after liver transplantation
Authors: Armenti Vincent T. , Herrine Steven K. , Radomski John S. , Moritz Michael J.
Published: March 2004

The first known posttransplantation pregnancy was in 1958 in a renal transplant recipient who had received a kidney from her identical twin sister. The first known posttransplantation pregnancy in a liver transplant recipient was in 1978. Information available from female kidney transplant recipients helped in the decision making involved in the management of this case, as well as those that followed. Over the last 20 years, issues specific to liver transplantation and pregnancy have been identified. Similar to the kidney transplant recipient population, when prepregnancy recipient graft function is stable and adequate, pregnancy appears to be well tolerated. Also similar to kidney transplant recipients, there has been no evidence of a specific malformation pattern among the children, and although prematurity and low birth weight occur, overall newborn outcomes have been favorable. Pregnancy in the setting of recurrent liver disease, such as recurrent hepatitis C, poses a potential problem among liver transplant recipients, as well as the possible adverse effects of immunosuppression on maternal kidney function. Also of significance, peripartum graft deterioration has more severe consequences in this transplant recipient population. Therefore, pregnancy must be considered carefully in this transplant recipient group. Since 1991, the National Transplantation Pregnancy Registry (NTPR) has studied the safety of pregnancy outcomes in solid-organ transplant recipients. The purpose of this review is to catalog studies in the literature, as well as to present current data from the registry with management guidelines.
Surgery and transplantation for hepatocellular cancer
Authors: Wall William J. , Marotta Paul J.
Published: March 2004

Key Points

1. Curative treatment of hepatocellular carcinoma (HCC) depends on early diagnosis.

2. The cure rate for operable HCC occurring in the absence of cirrhosis is only 10% to 25%.

3. Features of HCC in patients with cirrhosis that are associated with a 5-year survival rate of 75% after liver transplantation include (1) solitary tumor less than 5 cm; (2) 3 or fewer tumors, each less than 3 cm; and (3) absence of vascular invasion.

4. Advanced cirrhosis limits the widespread application of partial hepatectomy to patients with HCC.

5. Neoadjuvant therapy has not yet been proven to improve patient outcome for early-stage HCC that is promptly treated by transplantation.
Right-lobe living donor liver transplantation
Authors: Marcos Amadeo
Published: March 2004

Key Points

1. Living donor liver transplantation (LDLT) is currently performed at about 30 centers in the United States.

2. Careful and critical evaluation of donor and recipient is required for optimal outcome.

3. Right lobe donation is preferred over left lobe donation in adult LDLT.

4. There has been 1 donor death (<0.3%) in the US experiences. Donor biliary complications occur in approximately 4% of the cases.

5. Recipient survival after adult LDLT in the United States is approximately 88%. Hepatic artery thrombosis occurs in 3% and biliary complications in 18%.
Experience with the use of sirolimus in liver transplantation—use in patients for whom calcineurin inhibitors are contraindicated
Authors: Chang George J. , Mahanty Harish D. , Quan David , Freise Chris E. , Ascher Nancy L. , Roberts John P. , Stock Peter G. , Hirose Ryutaro
Published: March 2004

Sirolimus (SRL) provides effective immunosuppression for kidney transplantation and may be useful in patients with delayed allograft function after kidney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patients with renal insufficiency or acute mental status impairment were administered SRL after liver transplantation (5- to 10-mg load, 1 to 4 mg/d). Immunosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline mental status or serum creatinine level), tacrolimus (TAC) therapy was initiated. Twelve patients received primary transplants, 1 patient received a combined liver-kidney transplant, and 1 patient received a third transplant. Follow-up was 2 to 7 months. Calcineurin inhibitors were initially withheld in 9 patients, and therapy was aborted because of toxicity in the remaining 5 patients. Mean times to the initiation of SRL and TAC therapy were 5.4 ± 4.6 and 26.8 ± 24.4 days, respectively. Serum trough levels of SRL did not correlate with dose or other patient variables. Two patients died after prolonged pretransplantation hospital courses in the intensive care unit. Six patients experienced acute rejection, but only 1 patient required antilymphocyte therapy. Serum creatinine levels at the start of SRL therapy were 2.2 ± 1.1 and 1.2 ± 0.6 mg/dL at 3 months. All 3 patients with neurological indications for SRL had a return to their baseline mental status. All patients had improved liver function chemistry test results and prothrombin times. No patients developed leukopenia or thrombocytopenia. SRL is safe after liver transplantation in patients with acute neurological or renal impairment. SRL is an attractive alternative when calcineurin inhibitors are undesirable, but serum trough levels of SRL should be monitored. A prospective randomized study of an SRL-based calcineurin inhibitor-avoiding regimen compared with standard therapy in patients with renal insufficiency will further evaluate the role for SRL in liver transplantation.
Quality of life after liver transplantation for alcoholic liver disease
Authors: Pereira Stephen P. , Howard Louise M. , Muiesan Paolo , Rela Mohammed , Heaton Nigel , Williams Roger
Published: March 2004

There are few data on predictive factors for alcohol relapse or long-term functional outcome after liver transplantation for alcoholic liver disease (ALD). In all 56 surviving UK patients (47 men, 9 women; mean age: 51 years; range: 33 to 69 years) who underwent transplantation for ALD at King’s College Hospital over a 10-year period, alcohol relapse and outcome were assessed by outpatient and case-note review and by postal questionnaire containing (1) the Nottingham Health Profile (NHP), (2) the Short-Form-36 (SF-36) Health Survey, and (3) a drug and alcohol questionnaire. At a median of 2.5 years (range: 0.5 to 10 years), 13 of the 47 respondents (28%) and 2 of the 9 nonrespondents (22%) had evidence of potentially harmful drinking (>3 units daily) at some time posttransplantation. An additional 13 patients admitted to drinking some alcohol at least once, corresponding to an overall relapse rate of 50%. The patients with harmful drinking (1) had started drinking regularly at a younger age (18 v 25 years; P = .01), (2) began drinking heavily at a younger age (30 v 40 years; P = .01), (3) had shorter pretransplantation abstinence periods (10 v 23 months; P = .02), and (4) had a longer time since transplantation (median, 5.7 v 1.5 years; P = .0004) than those with no or mild alcohol relapse. They were also more likely to report sleep disturbance (NHP sleep problem score, 45 v 16; P = .01) and use benzodiazepines regularly (7 of 13 v 3 of 34 patients; P = .002). Despite these differences, health dimension scores in the SF-36 and NHP posttransplantation were similar between the groups and to those of UK community controls. In the long term, at least 50% of the patients will drink again at some time posttransplantation, although at lower levels of alcohol intake than previously. Those patients with multiple predictive factors for alcohol relapse may be at greatest risk for harmful drinking and be the group that would benefit most from professional counseling. Overall, the quality of life after liver transplantation for ALD is high and broadly similar to the levels expected in the normal population.
Increasing incidence and pretransplantation screening of hepatocellular carcinoma
Authors: Everson Gregory T.
Published: March 2004

Key Points

1. The incidence of hepatocellular cancer (HCC) in the United States and other traditionally “low-incidence” countries is increasing.

2. The rise in incidence of HCC is related to chronic hepatitis C.

3. Timely performance of liver transplantation is curative in patients with early-stage HCC.

4. Cirrhotic patients, especially those with viral hepatitis, should be screened for HCC.

5. The performance characteristics of current tests are suboptimal, but serial ultrasonography and alphafetaprotein are recommended.

6. Estimated medical charges related to screening and treatment suggest that $285,294 is required per “cured” case. Assuming that this cure is associated with a 75% to 85% chance for high-quality 10-year survival, the charges approximate $35,000 to $40,000/quality-adjusted life-year (QALY). This cost-benefit analysis is nearly identical to published rates for breast cancer screening ($30,000/QALY).
Long-term experience with lamivudine therapy for hepatitis B virus infection after liver transplantation
Authors: Ben-Ari Ziv , Mor Eytan , Shapira Zaki , Tur-Kaspa Ran
Published: March 2004

Hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is associated with a high recurrence rate and poor prognosis. This is the first study of the efficacy of long-term lamivudine therapy for patients with HBV infection after OLT. Eight patients (5 men, 3 women) aged 35 to 63 years (mean, 50 years) with HBV infection after OLT (6 patients, recurrent infection; 2 patients, de novo infection) were treated with lamivudine, 100 mg/d, on a compassionate-use basis. Before treatment, all had detectable HBV DNA in serum, and 5 patients (62.5%) had detectable serum hepatitis Be antigen (HBeAg). Duration of treatment was 24 to 50 months (mean, 36 months). Patients were monitored for serum alanine aminotransferase level (ALT), HBV DNA (by hybridization), hepatitis B surface antigen (HBsAg), and HBeAg before and after therapy, and liver histological findings were scored for inflammation and fibrosis. After treatment, 3 patients (32.5%) had undetectable HBV DNA by hybridization assay. None of the patients lost serum HBeAg and HBsAg, except for 1 patient who lost serum HBeAg and became serum antibody to HBeAg-positive. Serum ALT levels normalized in 5 patients (62.5%). Blinded histological assessment showed improvement in 1 patient, no change in 2 patients, and worsening in 5 patients. YMDD variants of HBV were detected in 5 patients (62.5%) within 9 to 20 months (mean, 13 months) of lamivudine therapy. Of these, 2 patients (40%) had hepatic failure (1 patient died of massive variceal bleed) and 3 patients remain clinically stable. Lamivudine therapy was continued in the latter patients. Although lamivudine is a potentially effective therapy for HBV infection after OLT, emergence of high mutation rates with long-term therapy, histological progression, and the possibility of hepatic failure point to the need to investigative combinations of antiviral therapy.
Acute changes in cerebral blood flow and metabolism during portasystemic shunting
Authors: Jalan Rajiv , Newby David E. , Damink Steven W.M. Olde , Redhead Doris N. , Hayes Peter C. , Lee Alistair
Published: March 2004

This report describes the instantaneous changes in cerebral blood flow (CBF), determined by intravascular ultrasound and Doppler, in a patient with cirrhosis undergoing placement of a transjugular intrahepatic stent-shunt for uncontrolled variceal bleeding. Acute changes in CBF were observed during and after portasystemic shunting, which culminated in cerebral edema and cerebral herniation.
Employment and alcohol use after liver transplantation for alcoholic and nonalcoholic liver disease: A systematic review
Authors: Bravata Dena M. , Olkin Ingram , Barnato Amber E. , Keeffe Emmet B. , Owens Douglas K.
Published: March 2004

The purpose of the study is to evaluate patterns of employment and alcohol use among liver transplant recipients with alcoholic (ALD) and nonalcoholic liver disease (non-ALD). MEDLINE, EMBASE, and bibliographic searches identified 5,505 potentially relevant articles published between January 1966 and October 1998. Eighty-two studies reporting data on 5,020 transplant recipients met our inclusion criteria. Pre—orthotopic liver transplantation (OLT), 29% of transplant recipients with ALD and 59% of those with non-ALD worked versus 33% and 80% at 3 years for transplant recipients with ALD and non-ALD, respectively (P < .00001 for each interval). We found no difference in the proportion of transplant recipients with ALD and non-ALD reporting early alcohol use post-OLT: 4% versus 5% at 6 months and 17% versus 16% at 12 months. However, among post-OLT drinkers, transplant recipients with non-ALD were more likely to drink moderately and those with ALD to drink excessively. At 7 years post-OLT, 32% of the patients with ALD reported using alcohol. The odds ratio for alcohol use among patients who maintained abstinence for fewer than 6 months pre-OLT versus those who maintained abstinence for greater than 6 months was 7.8 (95% confidence interval, 4.0 to 15.3). Before OLT and at long-term follow-up, substantially more transplant recipients with non-ALD than ALD were employed. The proportions of transplant recipients with ALD and non-ALD reporting alcohol use did not differ, although those with ALD tended to consume greater quantities.
Pancreatitis in adult orthotopic liver allograft recipients: Risk factors and outcome
Authors: Verran Deborah J. , Gurkan Alihan , Chui Albert K. , Dilworth Pamela , Koorey David , McCaughan Geoffrey , Sheil Ainslie G.R.
Published: March 2004

Acute pancreatitis (AP) has been described after orthotopic liver transplantation but is uncommon in stable patients after the initial perioperative phase. The aim of this study is to review our experience with AP occurring more than 2 months after primary allografting and determine possible contributing factors plus patient outcome. A review of patient files and the unit database was performed. AP was diagnosed in 9 of 298 patients (3%) on 12 occasions. The incidence of AP was greater in men (8 of 163 men) than women (1 of 135 women; P< .04). Underlying factors to each episode of AP were biliary manipulation (4 of 12 episodes; 33%), history of recent alcohol ingestion (3 of 12 episodes; 25%), and malignancy in the region of the pancreas (2 of 12 episodes; 16%). AP was associated with a diagnosis of either hepatic artery thrombosis combined with biliary tract complications (P< .005) or malignancy (P< .004). In 7 of 12 episodes of AP (58%), conservative management alone was successful. In 3 of 9 patients (33%), subsequent surgery was required. One patient died of pancreatic malignancy. In conclusion, AP is uncommon in stable liver transplant recipients. Male sex, complications of hepatic artery thrombosis, and malignancy in the region of the pancreas are associated with AP in this study.
Internal biliary stenting in orthotopic liver transplantation
Authors: Johnson Mark W. , Thompson Patricia , Meehan Ann , Odell Pat , Salm Jane M. , Gerber David A. , Zacks Steven L. , Fried Michael W. , Shrestha Roshan , Fair Jeffrey H.
Published: March 2004

Biliary complications account for significant morbidity in orthotopic liver transplantation (OLT), with a reported incidence ranging from 6% to 47%, and many centers are reassessing the need and options available for stenting the biliary anastomosis. We report on our experience using a 6F Silastic, double-J, ureteral stent as an internal biliary stent in OLT. From October 15, 1995, to September 30, 1998, a total of 99 patients at our institution underwent 108 OLTs. Of these, 77 patients received an end-to-end choledochocholedochostomy over an internal stent. Three patients died within 1 week post-OLT, leaving 74 patients for evaluation (follow-up, 2 to 38 months). Stents were placed transanastomotic and transsphincteric at the time of OLT and secured with a dissolvable suture. At 4 to 6 weeks post-OLT, stents visible within the biliary tree on kidney, ureters, and bladder radiograph were removed endoscopically. Graft and patient survival rates were 92% and 96%, respectively. There were 12 biliary complications (18%): anastomotic leak in 6 patients (9%), anastomotic stricture in 5 patients (7.6%), and stent migration in 1 patient (1.5%). Thirty-two patients (43%) passed the biliary stent without intervention, whereas 42 patients (57%) underwent esophagogastro duodenoscopy (EGD) stent removal at 4 to 6 weeks without incident. Treatment of the complications included percutaneous drainage, endoscopic dilatation with stenting, and/or conversion to Roux-en-Y choledochojejunostomy. The use of the 6 F Silastic, double-J, ureteral stent provides a safe and effective means of stenting the biliary anastomosis in OLT. Major advantages to this method are that it: (1) is completely internal, (2) is biliary decompressive, (3) is radiopaque, (4) can be spontaneously passed, and (5) is easily accessible for EGD extraction.
Early vascular complications after pediatric liver transplantation
Authors: Sieders Egbert , Peeters Paul M.J.G. , TenVergert Elisabeth M. , de Jong Koert P. , Porte Robert J. , Zwaveling Jan H. , Bijleveld Charles M.A. , Slooff Maarten J.H.
Published: March 2004

Vascular complications have a detrimental effect on the outcome after liver transplantation. Most studies focus exclusively on hepatic artery thrombosis (HAT). The current study analyzed the incidence, consequences, and risk factors for HAT, portal vein thrombosis (PVT), and venous outflow tract obstruction (VOTO) in a consecutive series of 157 pediatric liver transplantations. The overall incidence of vascular complications was 21%. The incidences of HAT, PVT, and VOTO were 10%, 4%, and 6%, respectively. Patient survival after PVT and VOTO and graft survival after HAT and PVT were less compared with survival of grafts without vascular complications. To identify risk factors for vascular complications, factors related to recipient, donor, and surgical techniques were analyzed. A low donor-recipient (D/R) age ratio, long surgical time, and use of the proper hepatic artery of the recipient for arterial reconstruction were risk factors for HAT. Young age, low weight, segmental grafts, and piggyback technique were risk factors for PVT. Fulminant hepatic failure, high D/R age and weight ratios, and use of segmental grafts were related to VOTO. Vascular complications, which occurred in 21% of the pediatric liver transplantations, had a significant impact on patient and graft survival. Size disparity between donor and recipient was an important risk factor for vascular complications, especially in the case of transplantation of segmental grafts. Patient and graft survival might improve by avoiding the identified risk factors.
Laparoscopic cholecystectomy and cirrhosis: A case-control study of outcomes
Authors: Fernandes Neville F. , Schwesinger Wayne H. , Hilsenbeck Susan G. , Gross Glenn W.W. , Bay Michael K. , Sirinek Kenneth R. , Schenker Steven
Published: March 2004

The incidence of gallstone disease in patients with cirrhosis is greater than that in healthy patients. Previous surgical literature reported greater morbidity and mortality in patients with cirrhosis with both open and laparoscopic cholecystectomy (LC). We compared our recent experience with LC in patients with cirrhosis and controls. A retrospective review was performed using the search terms, “cirrhosis” and “laparoscopic cholecystectomy.” Forty-eight patients with cirrhosis were identified and randomly matched with healthy controls by age and sex. Four controls were assigned per patient with cirrhosis. Outcomes assessed included mortality, duration of surgery, length of hospital stay, blood transfusion requirement, postoperative complications, and need for conversion to open cholecystectomy. Forty-eight patients with cirrhosis and 187 healthy controls underwent LC. Child-Pugh classification of severity of liver disease was as follows: Child’s class A, 38 of 48 patients; Child’s class B, 10 of 48 patients; and Child’s class C, 0 of 48 patients. Patients with cirrhosis had statistically significantly lower albumin levels (P = .0001) and prolonged prothrombin times (P = .05). Average duration of surgery for patients with cirrhosis was 1.71 versus 1.57 hours (P = .57) for controls. Average length of hospital stay for patients with cirrhosis was 6.47 versus 4.77 days (P = .152) for controls. Average number of units of blood transfused in patients with cirrhosis was 0.156 versus 0.0 units (P = .025) in controls. Complications occurred in 6 of 48 patients with cirrhosis (12.5%) and 8 of 187 controls (4.2%; P < .05). No child’s class C patient underwent LC. Four patients with cirrhosis (8.3%) and no controls were converted to open cholecystectomy. No postoperative infections were noted. There was no mortality in either group. LC in patients with Child’s class A and B cirrhosis is reasonably safe and shows no increase in morbidity or mortality or worsening of outcome. Further studies are required to evaluate the management of acute gallbladder disease in Child’s class C patients.
Single-center analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe
Authors: Marcos Amadeo , Ham John M. , Fisher Robert A. , Olzinski Ann T. , Posner Marc P.
Published: March 2004

The first adult-to-adult living donor liver transplant using the right hepatic lobe in the United States was performed only 2 years ago. Although initial reports were encouraging, continuous review of the results and appropriate modifications in patient management will be necessary to minimize donor risk and optimize recipient outcome. The results of 40 such transplantations were analyzed and are summarized. Recipients were listed for transplantation according to the usual criteria. Living donors were not considered for United Network for Organ Sharing status IIA patients after the initial 22 patients. Donor evaluation followed a rigid protocol. A graft-to-recipient body weight ratio of at least 0.8% was the minimum required throughout most of the study. The surgical procedures were similar, except the plane of transection was modified to better accommodate donor biliary anatomy, and uniform stenting of bile ducts was practiced after the first 10 transplants. Immunosuppression consisted of tacrolimus, mycophenolate mofetil, and a prednisone taper. The target tacrolimus level was decreased and mycophenolate was withdrawn more rapidly in the second half of the study because of the absence of acute cellular rejection. Donor morbidity has been limited to minor complications, and transplant recipient biliary complications decreased from 35% to 0%. Acute cellular rejection has not been observed despite less aggressive immunosuppression, and septic complications decreased dramatically. There have been no recipient deaths since these changes were instituted. Right lobectomy can be performed safely in the donor population. Recipient biliary complications can be minimized with stenting. Less aggressive immunosuppression is well tolerated and minimizes septic complications and attributable mortality.
A direct-numerical-simulation-based second-moment closure for turbulent magnetohydrodynamic flows
Authors: Kenjereš S. , Hanjalić K. , Bal D.
Published: March 2004

A magnetic field, imposed on turbulent flow of an electrically conductive fluid, is known to cause preferential damping of the velocity and its fluctuations in the direction of Lorentz force, thus leading to an increase in stress anisotropy. Based on direct numerical simulations (DNS), we have developed a model of magnetohydrodynamic (MHD) interactions within the framework of the second-moment turbulence closure. The MHD effects are accounted for in the transport equations for the turbulent stress tensor and energy dissipation rate—both incorporating also viscous and wall-vicinity nonviscous modifications. The validation of the model in plane channel flows with different orientation of the imposed magnetic field against the available DNS (Re=4600,Ha=6), large eddy simulation (Re=2.9×104,Ha=52.5,125) and experimental data (Re=5.05×104 and Re=9×104, 0⩽Ha⩽400), show good agreement for all considered situations.
Psychiatric Comorbidity in Treatment‐Seeking Alcoholics: The Role of Childhood Trauma and Perceived Parental Dysfunction
Authors: Langeland Willie , Draijer Nel , van den Brink Wim
Published: March 2004

Abstract: Background: This study among treatment‐seeking alcoholics examined the relationship between childhood abuse (sexual abuse only [CSA], physical abuse only [CPA], or dual abuse [CDA]) and the presence of comorbid affective disorders, anxiety disorders, and suicide attempts, controlling for the potential confounding effects of other childhood adversities (early parental loss, witnessing domestic violence, parental alcoholism, and/or dysfunction) and adult assault histories.

Method: We assessed 155 (33 females, 122 males) treatment‐seeking alcoholics using the European Addiction Severity Index, the Structured Trauma Interview, and the Composite International Diagnostic Interview.

Results: The severity of childhood abuse was associated with posttraumatic stress disorder (PTSD) and suicide attempts in females and with PTSD, social phobia, agoraphobia, and dysthymia in males. Among men, multiple logistic regression models showed that CPA and CDA were not independently associated with any of the examined comorbid disorders or with suicide attempts. However, CSA independently predicted comorbid social phobia, agoraphobia, and PTSD. For the presence of comorbid affective disorders (mainly major depression) and suicide attempts, maternal dysfunctioning was particularly important. CSA also independently contributed to the number of comorbid diagnoses. For females, small sample size precluded the use of multivariate analyses.

Conclusion: Childhood abuse is an important factor in understanding clinical impairment in treated alcoholics, especially regarding comorbid phobic anxiety disorders, PTSD, and suicidality. These findings underline the importance of routine assessment of childhood trauma and possible trauma‐related disorders in individuals presenting to alcohol treatment services. More studies with bigger samples sizes of female alcohol‐dependent patients are needed.
Age at First Drink Relates to Behavioral Measures of Impulsivity: The Immediate and Delayed Memory Tasks
Authors: Dougherty Donald M. , Mathias Charles W. , Tester Melissa L. , Marsh Dawn M.
Published: March 2004

Abstract: Background: This study examined the relationship between laboratory‐measured impulsivity and age at first drink.

Methods: Using a laboratory behavioral measure of impulsivity [Immediate (IMT) and Delayed Memory Tasks (DMT)], we compared two groups of women differing in their self‐reported age at first drink (early‐onset drinking, age <18 years, n= 40; late‐onset drinking, age ≥21 years, n= 23). It was expected that those who first consumed alcohol before the legal drinking age (i.e., early onset) would perform in a more impulsive manner on the laboratory behavioral measure than the late‐onset drinkers.

Results: The main finding was that the early‐onset group (IMT: mean, 28.7%; DMT: mean, 30.4%) had increased commission error rates compared with the late‐onset group (IMT: mean, 21.2%; DMT: mean, 15.5%) during both the IMT [ANOVA:F (1,61) = 4.30; p= 0.042; f= 0.27] and DMT [F (1,61) = 10.76; p= 0.002; f= 0.42]. Age at first drink was significantly correlated with DMT commission errors (r=−0.23; p= 0.037), although this was only at the trend level for IMT commission errors (r=−0.20; p= 0.062); these correlations are likely to be underestimates because of range restriction of the age variable.

Conclusions: These results demonstrate that differences in impulsive behavioral responding are distinguishable even between groups of alcohol drinkers who are not experiencing clinically significant problems with alcohol.