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Acute liver failure (ALF) is a clinical syndrome associated with significant morbidity and mortality with a highly unpredictable outcome. We retrospectively analyzed 71 ALF patients (53 males; mean age = 27.5 ± 15.6 years) that underwent transjugular liver biopsy (TJLB) at our institution. The aims of this study are (i) to report our experience with TJLB in these patients, and (ii) to examine the role of liver histology in predicting their outcome. We also compared the histopathological findings between TJLB and explanted liver specimens in 31 patients who underwent liver transplantation (LT). Biopsy specimens were satisfactory for histopathological analyses in 69 (97.1%) patients, confirmed the clinical diagnosis in 56 (81.2%) patients, and altered the diagnosis in 13 (18.8%) patients. Minor complications were encountered in four (5.6%) patients. Percentage of hepatocyte necrosis was the only histological parameter that has significant discriminatory prognostic value, with no survivors having >75% necrosis without LT. In conclusions, TJLB is a safe technique for obtaining liver tissue in both adult and pediatric patients with ALF. Histological characteristics, mainly etiological diagnosis and degree of hepatocyte necrosis may assist in clinical decision-making for need of LT in these patients.

Peroral cholangioscopy with its limitations led to further research regarding development of SpyScope® technology. The aim of this retrospective study was to investigate the efficacy of a new device and the application of this device in our Liver Transplant Center.Charts of patients who had undergone evaluation with SpyScope® were retrospectively reviewed. Indications included pre-transplant as well as post-transplant evaluation of biliary strictures. If strictures or filling defects were noted by cholangiogram, SpyScope® was performed. Biopsy was obtained under direct visualization if necessary with SpyBite® biopsy forceps. Demographic features, indications for SpyScope® evaluation, results, and histopathological diagnoses were recorded.Ten patients (6 male, 4 female; median age: 55) had undergone SpyScope® procedure between August 2007 and January 2008. Six out of 10 cases were in the pre-transplant work-up period, referred to as Group I, while the remaining four were post-transplant patients, referred to as Group II. In Group I, 4 of 6 cases had undergone the procedure for work-up of primary sclerosing cholangitis prior to orthotopic liver transplantation. In Group II, indications were either strictures noted during the previous endoscopic retrograde cholangiopancreatography (n=2) or common bile duct stones with elevated total bilirubin levels and stones with long segment biliary stricture (n=2). In the patient with anastomotic stricture, the biliary lithiasis was eventually exposed just above the anastomotic stricture, after abundant lavage was applied at that level. All SpyBite® biopsy specimens were reported to be adequate samples for histopathological examination. No malignancy was detected among 4 patients with primary sclerosing cholangitis and patients with elevated CA 19-9.SpyScope® allows direct visualization of biliary strictures and SpyScope®/SpyBite® were found to be technically superior to conventional cholangiogram with better sampling than brushing obtained by endoscopic retrograde cholangiopancreatography. Prospective, multicenter, large volume studies are warranted to identify its sensitivity and specificity.

Hepatic Artery thrombosis remains one of the major causes of graft failure and mortality in liver transplant recipients. Urgent re-transplantation has been considered as mainstay therapy; however, even with re-transplantation mortality of more than 50% has been reported by many series. Early detection on Doppler ultrasonography and subsequent revascularization in asymptomatic patients can avoid graft loss. Endovascular therapy including intra-arterial thrombolysis, percutaneous transluminal angioplasty, and stent placement have shown encouraging results in recent years; nevertheless, their use remains controversial due to potential risk of bleeding. We present a case of early hepatic artery thrombosis following liver transplantation treated successfully with continuous transcatheter intra-arterial thrombolysis using tissue plasminogen activator (t-PA).

Background Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay. Methods Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values. Results A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients. Conclusion These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability.

Total plasma exchange (TPE) corrects coagulopathy in patients with liver disease and removes hepatotoxins/cytokines. This improvement is transient but can be used as a bridge until an organ is identified for liver transplantation (LTx) or the liver itself regenerates. Our aim was to retrospectively assess the efficacy of TPE in fulminant hepatic failure (FHF) and its impact on liver function tests. Between 1995-2001, 39 patients with FHF who had undergone TPE were reviewed. FHF was defined according to the O'Grady criteria based on the duration of encephalopathy as well as jaundice. TPE was performed using the Cobe Spectra TPE (Gambro) in Liver Intensive Care Unit, continued on a daily basis, until either adequate clinical response was achieved, the patient expired, or transplantation occurred. INR, PTT, Fibrinogen, ALT, AST, GGT, BUN, Ammonia, and Total Bilirubin were analyzed before and after TPE. Student's t-test and chi-square test and ANOVA were used for statistical analysis. Thirty-nine patients with FHF (31 females, 8 males with mean age of 32.3, range: 7-64) underwent TPE. Coagulopathy, hyperbilirubinemia, hyperammonemia were significantly improved (P < 0.05). Twenty-one patients survived (54%), 12 required LTx, and 18 patients (including one after LTx) expired. TPE was found to be significantly effective for correction of coagulopathy and improvement of liver tests. This intervention can be considered for temporary liver support until recovery or liver transplantation.

Aim To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. Method We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. Results Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. Conclusion HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.

Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1β correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV.

Fulminant hepatic failure (FHF) carries a high mortality. We aimed to review the prognostic factors and explore the potential role of Liver Dialysis (LD). Fifty-two patients were reviewed. The etiologies were acetaminophen toxicity (33%), viral hepatitis (18%), autoimmune (10%), idiosyncratic drug reactions (8%), others (6%) and undetermined (25%). Patients with acetaminophen had a significantly higher survival compared to the non-acetaminophen group (p=0.04). Patients with grade 3 encephalopathy had a mortality of 68%, among 5 patients with grade IV encephalopathy, 2 survived and both had had treatment with LD. Chi-square with Fisher's exact test was used for statistical analysis. Our study confirmed that the diagnosis of non-acetaminophen induced FHF and reduced initial serum factor V level are associated with fatal outcome. Timely OLT significantly improved the survival. The role of LD in hepatic regeneration or as a bridge to OLT needs to be further studied with prospective control trials.

Background & Aims: There is growing evidence that the interplay of genetic susceptibility and environmental factors leads to primary biliary cirrhosis (PBC). In particular, family members of an infected individual have up to a 100-fold higher risk of developing PBC. Although concordant rates for identical twins in other autoimmune diseases range between 25% and 50%, there are no such data on PBC. Accordingly, we evaluated the concordance of PBC in a genetically defined population of twin sets and evaluated the clinical characteristics between concordant subjects. Methods: We identified 16 pairs of twins within a 1400-family cohort followed up by several centers worldwide, evaluated the diagnosis of PBC in all individuals, and determined the zygosity of sets reported as identical by the analysis of 2 highly variable HLA class II regions and 5 short tandem repeats. Results: Eight of 16 sets of twins were monozygotic. In 5 of 8 monozygotic twin sets, both individuals had PBC (pairwise concordance rate, 0.63). Among the dizygotic twins (n 8), no set was found to be concordant for PBC. Interestingly, the age at onset of disease was similar in 4 of 5 concordant sets of monozygotic pairs; however, there were differences in natural history and disease severity. Conclusions: The concordance rate of PBC in identical twins is among the highest reported in autoimmunity. However, discordant pairs were identified. The data show not only the role of genetics but also emphasize that either epigenetic factors and/or environment play a critical role.

Bile duct hamartomas (von Meyenburg complex) are the rare benign neoplasm of the liver due to dysembryogenesis; constituted historically, cystic dilatations of the bile duct encompassed by fibrous stroma. Usually, they are asymptomatic and are not detected on routine radiological examinations including ultrasound or CT scan. Magnetic resonance cholangiography has been suggested as the best investigation for their imaging diagnosis. Their presence can cause diagnostics confusion and complicate the patient's management. We report a 45-year-old female with symptomatic cholelithiasis, whose liver on laparoscopy mimicked multiple hepatic metastases.

Thrombocytopenia is a frequent complication of cirrhosis. Its pathogenesis is not well known, but it has been suggested that splenic congestion induced by portal hypertension may be a major contributory factor. However, the available data regarding the effect of portal decompression either by surgical shunts or transjugular intrahepatic portosystemic shunt (TIPS) on peripheral platelet count in cirrhotics is conflicting. We studied the effects of TIPS on platelet count and mean platelet volume, following a successful TIPS placement. The platelet count had a tendency to decrease but was not statistically significant (120,100 ± 72,100/mm3 before TIPS vs 99,800 ± 51,400/mm3 after TIPS). The mean platelet volume remained essentially unchanged (9.8 ± 1.5 fL before TIPS and 9.9 ± 1.5 fL after TIPS). These results confirm that TIPS has an unpredictable effect on platelet count in cirrhotic patients with thrombocytopenia. The lack of a consistent increase in the peripheral mean platelet volume following TIPS placement suggests that TIPS is unable to significantly enhance the release of platelets sequestered in the splenic compartment in portal hypertension.

Among extracorporeal liver support devices, liver dialysis is cleared by the U.S. Food and Drug Administration to be used for the management of fulminant hepatic failure (FHF). The outcomes of patients following liver dialysis need to be clearly evaluated. Among the 25 patients with FHF admitted to the Liver ICU between May 2000 and November 2002, 12 underwent liver dialysis, including 6 men and 6 women, of mean age 32 years. The causes of FHF were identified as acetaminophen ( n = 10), herbal medications ( n = 1) and autoimmune disease ( n = 1). At presentation, the mean total bilirubin was 9.35 mg/dL (range, 0 to 1.3), mean ALT 3015 U/L (range, 0 to 48), mean AST 3457 (range, 0 to 42), mean ammonia 98 μmol/L (range, 10 to 60) and mean INR 1.88. A control group including 13 patients (2 men and 11 women), of mean age 27.8 years mean total bilirubin 5.66, mean ALT 3494, mean AST 3528, mean ammonia 113 and mean INR 3, were not treated with liver dialysis, due to the lack of machine availability or physician’s choice. The causes of FHF were acute hepatitis B ( n = 1), acetaminophen ( n = 10) or unknown ( n = 2). There was no statistically significant difference in the baseline characteristics of the two groups ( P > .05). Among the liver dialysis group, 1 patient died, 2 underwent OLTx, and 9 were discharged home. Among the control group; 4 patients died, 2 underwent OLTx, and 7 were discharged home. Preliminary results seem to support survival benefit among patients who underwent liver dialysis compared to non–liver dialysis; however, further randomized control trials are warranted to verify this observation.

Acute liver failure (ALF) is a clinical syndrome associated with significant morbidity and mortality with a highly unpredictable outcome. We retrospectively analyzed 71 ALF patients (53 males; mean age = 27.5 ± 15.6 years) that underwent transjugular liver biopsy (TJLB) at our institution. The aims of this study are (i) to report our experience with TJLB in these patients, and (ii) to examine the role of liver histology in predicting their outcome. We also compared the histopathological findings between TJLB and explanted liver specimens in 31 patients who underwent liver transplantation (LT). Biopsy specimens were satisfactory for histopathological analyses in 69 (97.1%) patients, confirmed the clinical diagnosis in 56 (81.2%) patients, and altered the diagnosis in 13 (18.8%) patients. Minor complications were encountered in four (5.6%) patients. Percentage of hepatocyte necrosis was the only histological parameter that has significant discriminatory prognostic value, with no survivors having75% necrosis without LT. In conclusions, TJLB is a safe technique for obtaining liver tissue in both adult and pediatric patients with ALF. Histological characteristics, mainly etiological diagnosis and degree of hepatocyte necrosis may assist in clinical decision-making for need of LT in these patients.

Objective: To determine the prevalence of acute sinusitis by physical examination and radiology in individuals presenting for liver transplantation. Design: One hundred consecutive individuals presenting for a liver transplant were studied prospectively for evidence of acute sinusitis. Forty-eight spouses, relatives or partners accompanying the patient to the transplant center agreed to act as controls. Setting: Tertiary referral hospital. Methods: A complete physical examination was performed with particular attention to the eyes, ears, nose and naso-oropharynx. A series of sinus radiographs were also taken consisting of anterior, posterior, lateral, Caldwell and Waters views of the nasal sinuses; air fluid levels within the sinuses were assessed. Results: Thirty-eight per cent of the patients, but only 8.5% of the controls, had radiologic evidence of sinus pathology (P < 0.01). The maxillary sinuses were predominantly involved and mucosal thickening was the most frequent radiologic evidence of sinusitis. Conclusions: These data suggest that sinus pathology occurs at an increased rate in individuals with advanced liver disease and that the pathology is characterized by mucosal thickening in association with an air fluid level.

Twenty-four subjects with chronic HCV infection were treated with IFN for six months. Liver biopsies were obtained before and after therapy. The number of mononuclear cells staining for CD3, CD4, CD8, 3G8, and the number of mononuclear cells, liver cells, and bile duct cells staining for class I and II MHC antigens in the biopsies was determined. NK cells increased from 16±3 to 28±3 cells per 5 high-power fields (HFP) (P≤0.03). The number of bile duct cells expressing class I and II MHC Ag and liver cells expressing class II MHC Ag increased (allP≤0.03). The only parameter that distinguished responders from nonresponders was the number of NK cells. Following IFN withdrawal, expression of these antigens declined. Based upon these data, it is concluded that IFN treatment of HCV increases: (1) the NK cells number; (2) the expression of class I MHC Ag on bile duct cells and the expression of class II MHC Ag on liver and bile duct cells; and (3) with IFN withdrawal, these changes disappear.

Seventy-nine subjects (19 women and 60 men) with chronic viral hepatitis were studied to determine the role of hepatic iron and its biochemical correlates in determining response to interferon alpha therapy. Each subject was treated for 6 months with interferon alpha. A total of 45 (57%) subjects achieved either a full or partial response. No differences between responders and non-responders were evident for the type of hepatitis, age, initial alanine aminotransferase, serum iron, total iron binding capacity, %sat, or ferritin. In contrast, the hepatic iron content of non-responders was almost twice that of responders (1156 +/- 283 micrograms/g dry weight vs. 638 +/- 118; p < 0.05). Hepatic iron correlated with total iron binding capacity (r = 0.435) and ferritin (r = 0.585). This study showed that: 1) the hepatic iron content of responders is less than that of non-responders, 2) the relationships of hepatic iron with %sat and ferritin in patients with viral hepatitis are weak, and 3) hepatic iron content predicts a response to interferon therapy.

Chronic HBV infection is a dynamic state of interaction between HBV, hepatocytes, and the immune system of the host. A series of reactivation flares and remissions may occur due to multiple causes. Among them, spontaneous reactivation and immunosuppressive drugs including steroids or cancer chemotherapy are well known. This is due to immune-mediated destruction of HBV-expressing cells following withdrawal of immunosuppressive effect. Few cases have been reported in females during postpartum period. We report a case of fulminant hepatic failure during pregnancy in a previously unrecognized hepatitis B positive female requiring emergent liver transplantation.

From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 ±1.7 years) than nonsurvivors (53.6 ± 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p

Liver transplantation (OLTx) has become a common life-saving procedure for individuals with chronic advanced liver disease. It is also used in the clinical treatment of patients with fulminant hepatic failure and those with primary neoplastic disease of the liver. Despite its overall success in restoring meaningful life to those who undergo the procedure, the posttransplant life of a liver allograft recipient is not without hazard. A common problem following liver transplantation is the finding of abnormal liver injury tests reflecting a "hepatitis" that can not be ascribed to allograft rejection. The majority of such cases are a consequence of either a technically flawed operation, drug-induced liver injury, or one or another form of viral hepatitis. Each of these problems is discussed in the following clinical review.

Hepatic artery thrombosis (HAT) is the most frequent vascular complication following orthotopic liver transplantation. Urgent retransplantation has been considered as the mainstay therapy. Surgical revascularization is an effective alternative in asymptomatic patients. Endovascular therapies including intra-arterial thrombolysis, percutaneous transluminal angioplasty (PTA), and stent placement have shown encouraging results in recent years; however, their use remains controversial because of potential risk of hemorrhage. Until June 2009, 69 cases were published in 16 reports describing therapeutic potential of endovascular modalities. Interventions were performed as early as within 4 h to as late as 120 days in patients ranging from 4 months to 64 years of age. Majority of published reports suggested the use of urokinase. Thrombolysis was successful in 47 out of 69 (68%) patients. Bleeding was the most common complication including fatal intra-abdominal hemorrhage in three patients. Twenty-nine out of 47 (62%) patients underwent further intervention in the form of PTA, stenting, or both. The follow-up patency ranged from 1 month to 26 months. In conclusion, whenever possible, efforts should be made to rescue the liver grafts through urgent revascularization (surgical and/or endovascular) depending on patient's condition and interventional expertise at the transplant center; reserving the option of retransplantation for failure, complications, and cases with severe clinical symptoms or allograft dysfunction.

Ciliated foregut cysts of the liver are rare, with only 96 cases diagnosed since the first description in 1857. They are being increasingly diagnosed recently; the majority of the cases have been reported in the last 15 years. Although they bear a close resemblance to the simple cyst of the liver which has essentially a benign course, ciliated hepatic foregut cysts (CHFCs) can progress to malignancy with devastating consequences. It is imperative that this group of conditions be diagnosed and treated adequately.This review includes discussion of the data from all the 96 reported cases from English and non-English literature. Analysis of the incidence rates, embryogenesis, growth, clinical features, risk of malignancy and the prognosis are highlighted systematically. The roles of various diagnostic modalities including ultrasound, CT, MRI, fine needle aspiration cytology (FNAC), immunohistochemistry and surgery are further discussed.The mean age of patients with CHFC was 48+/-12 years. The male/female ratio was 1.1:1. The majority of patients with CHFC (62%) were asymptomatic, and the common mode of presentation was right upper abdominal pain. The cysts occurred in the left lobe in 51 patients, with sole location in segment IV in 44, and in the right lobe in 26. The average size of the cysts was 3.6+/-2.12 cm. The majority of the cysts were unilocular, and only 7 cases were multilocular. Cyst contents were described as viscous or mucinous in 73 patients, whereas bilious fluid was noted in 3. Large cysts having squamous carcinoma were cited in 3 patients, and 2 had extensive squamous metaplasia without malignancy. Others had benign histopathology.Clinicians have become increasingly aware of CHFC. Imaging alone is not diagnostic per se, but when considered in the context of the global picture does provide important clues to the diagnosis. FNAC is diagnostic by the presence of the ciliated columnar aspirate but lacks sensitivity. Infantile presentation is usually accompanied by biliary communication and mandates a different surgical approach. The demonstration of malignant transformation in 3 cases and its fatal course emphasizes the need for surgical resection in all cases once the diagnosis is made.

Ciliated hepatic foregut cyst is a rare foregut cystic developmental malformation. It presents as a solitary cystic lesion in segment four of the liver. Histologically, it consists of four distinct layers; namely, the inner ciliate columnar epithelium, subepithelial connective tissue, smooth muscle layer, and an outer fibrous layer. Usually asymptomatic and detected incidentally, other modes of presentation can include portal hypertension, obstructive jaundice, and development of malignancy. We present a case of a young asymptomatic woman with a complex cyst in segment four of the liver, who underwent a laparoscopic resection, focusing our discussion on the review of the literature and the diagnostic dilemma encountered in these rare cases.

Introduction Early allograft dysfunction (EAD) is a rare but serious complication encountered among patients undergoing liver transplant surgery. Total plasma exchange (TPE) in EAD has been suggested, but its role is still considered investigational. We retrospectively assessed the efficacy of TPE in EAD and its impact on other parameters of liver function. Materials and methods Between 1995 and 2001, 25 orthotopic liver transplant recipients developed EAD, which was defined as early postoperative prothrombin time (PT) >17 seconds, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2500 IU/L, and/or the presence of hepatic encephalopathy, and development of renal failure. Daily TPE was performed using the Cobe Spectra TPE (Gambro) for 4 hours until an adequate clinical response, the patient underwent retransplantation, or the patient died. International normalizing ratio (INR), partial thromboplastin time (PTT), fibrinogen, ALT, AST, gamma-glutanyl transpeptidase (GGT), blood urea nitrogen (BUN), ammonia, and total bilirubin were analyzed before and after TPE. Student t and chi-square tests were used for statistical analysis. Results Twenty-five patients with EAD included 13 females, 12 males of mean age 42.3 years (range, 1–63 years). Coagulopathy and hyperbilirubinemia significantly improved with TPE. Nineteen patients (76%) survived and 2 required retransplantation. Mean number of TPE sessions was 4.3. Conclusion TPE was effective to correct coagulopathy and improve liver function. These results suggest the benefit of potential temporary liver support until recovery or retransplantation, in the absence of sepsis or multi-system organ failure.

IgA deficiency is associated with high mortality (42% at 120 days) following liver transplantation (OLTx). Most of the mortality has been associated with enteric infections. Mother's milk, or human breast milk (HBM), is a rich source of IgA that is considered to have beneficial effects in terms of protection from microbial translocation and enteric infections. Two IgA-deficient OLTx recipients were given HBM orally for 10 days perioperatively. HBM was given in order to replenish intestinal IgA. Both patients had an excellent infection-free post-operative course. IgA levels in the serum rose from 5 to 10 mg/dl in one patient and from 7 to 30 mg/dl in the other. No complications from HBM administration were observed. We conclude that HBM can be used in IgA-deficient liver transplant recipients to reduce the risk of infectious complications in the post-operative period.

Utilization of endoscopy to both visualize and selectively biopsy an intestinal allograft has become the standard for early recognition and treatment of intestinal allograft rejection. Despite the widespread acceptance of the need for selective mucosal biopsies, it has not been shown that the histological features of intestinal allograft rejection are either localized or occur as part of a more diffuse phenomenon within a tubular allograft. To resolve these issues, 88 ileoscopies were performed in 12 small-bowel allograft recipients and mucosal biopsy samples were obtained at 5, 10, and 15 cm, respectively, from the ileal stoma. Each mucosal biopsy was labeled, processed, and evaluated individually for the presence and severity of any evidence for allograft rejection. The data obtained suggest that intestinal allograft rejection is a diffuse process, and biopsies obtained randomly from an ileal graft are likely to demonstrate evidence of allograft rejection when such is present.

Purpose The aim of this study was to determine serum prostate-specific antigen (PSA) levels in patients with liver cirrhosis. Patients and methods Between January 1995 and August 2001, 216 men with cirrhosis were evaluated. The extent of their liver disease was classified according to the Child-Pugh classification. Serum PSA levels were measured with the Hybritech Tandem-R RIA method and matched with age-related reference PSA levels. Digital rectal examination (DRE) was performed in all patients. Patients with elevated PSA levels and/or abnormal DRE were recommended to undergo further assessment including transrectal ultrasonography (TRUS) and biopsy performed by an urologist. Results Two hundred and sixteen men (mean age 54.09±9.09 years, range 25–76) with cirrhosis were examined. Their mean PSA value was 0.57±0.84 ng/mL and tended to be lower than in the normal population. The degree of PSA decrease was found to parallel the severity of the liver disease (p=0.002). The mean serum PSA level increased with each age decade in a statistically significant manner (pConclusion Serum PSA is influenced by the severity of liver disease and its levels tend to be lower in cirrhotic patients than in the normal population. However, serum PSA can still be considered a reliable marker in the clinical management of prostatic disease in patients with cirrhosis.

Liver biopsy is a frequently utilized diagnostic tool at a liver transplant center. It is occasionally utilized prior to OLTx to determine whether or not a potential recipient either has tumor or a disease process that has some chance of spontaneous recovery without OLTx. Following OLTx, it is often utilized to determine the need to alter a recipient's immunosuppression regiment or gauge the response to a recent change in immunosuppression

Currently, alpha interferon is the only recognized therapy for chronic viral hepatitis. As a result of its success in several multicenter trials, the agent was approved recently by the FDA for use in the clinical management of patients with chronic hepatitis C. FDA approval for its use in chronic hepatitis B is anticipated. Based upon this experience in nonimmunosuppressed individuals, the efficacy of alpha interferon therapy in patients who are recipients of liver allografts and are receiving chronic immunosuppression was assessed in a preliminary trial of the agent in 30 patients (13 with HBV, 11 with HCV, and 6 with hepatitis non A, non B, non C). Therapy was initiated at a dose of 3 X 10(6) units three times per week and continued for 6 months. Dose reduction in the amount of the alpha interferon administered was determined by a preestablished protocol. Nine percent of those with HCV and 18% of those with hepatitis non A, non B, non C experienced a full response to alpha interferon therapy. No full responses to alpha interferon therapy. No full responses were seen in those with HBV disease. Partial responses were common in all three groups but were most frequent in those with hepatitis non A, non B, non C and least frequent in those with HCV-related disease. This preliminary experience demonstrates the following: 1. Viral hepatitis following OLTx can be treated with alpha-2b-interferon. 2. The complications of alpha-2b-interferon therapy utilized prior to OLTx can be avoided by giving the therapy following successful OLTx. 3. The high rate of partial responses noted suggests that future studies should utilize either higher doses or longer durations of therapy or both. 4. The response rate was greatest for those having non A, non B, non C hepatitis and least for those with HCV hepatitis. 5. In this small preliminary series, no episodes of liver graft rejection could be ascribed to the use of alpha-2b-interferon in the patients so treated.

Alcoholic liver disease is a major cause of liver disease and has become an ever-increasing indication for liver transplantation (LTx). Follow-up studies have reported a higher rate of alcohol recidivism in patients transplanted for alcoholic hepatitis, compared with those transplanted for endstage alcohol-associated cirrhosis. It is assumed widely that recurrent alcohol use is associated with reduced compliance with immune suppression and, as a result, an increased risk of graft rejection and loss. To assess this question, 209 alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with a mean follow-up of 4.4 ± 0.6 years. There were 175 episodes of acute cellular rejection (ACR) that occurred in 137 patients, for an overall rejection rate of 83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was three times as great in those who remained alcohol-abstinent (2.24 episodes/patient), compared with those who admitted to continued alcohol use (0.75 episodes/patient) (p < 0.01). A total of 33 episodes of chronic rejection occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR, the chronic rejection rate was greater among those who were continuously alcohol-abstinent, compared with those who intermittently used alcohol after successful LTx. There were no differences in the mean FK 506 or cyclosporin A levels in the groups with and without a rejection episode at the time the rejection episode was documented by liver biopsy. Contrary to generally accepted opinion, these data suggest that continued use of alcohol by liver transplant recipients is associated with a reduction, not an increase, in the rate of rejection.

Purpose: Ideally, organ grafting is usually carried out between recipient and donor of identical blood group to minimize the influence of blood group specific antigens on graft and patients survival. The shortage of suitable donor organs and the clinical urgency can lead in to implantation of grafts from ABO mismatched donors. In liver transplantation, it has been suggested that patient and graft survival is diminished with the implantation of ABO incompatible grafts. Indeed, 1-year graft survival in this setting has been reported to range between 25% and 75% less than that of ABO-identical or compatible grafts. We reviewed and compared our experience with transplantation of ABO identical and compatible mismatched livers.

Neonatal hepatitis is a syndrome of unknown etiology occurring in children with viral liver disease, as well as children with unidentified disorders of bile salt synthesis and other poorly understood metabolic diseases. It is characterized by jaundice, giant cell hepatitis and rare liver failure necessitating liver transplantation. In the present investigation, the outcome of liver transplantation performed in 16 children with neonatal hepatitis at the investigators' institution was determined from 1 January 1989 to 31 December 1991. The results were compared to those obtained in 288 children transplanted for biliary atresia and 66 children transplanted for recognized metabolic liver disease. The children transplanted for neonatal hepatitis (4.1 +/- 1.3 years) and metabolic liver disease (5.8 +/- 0.6 years) were older than those transplanted for biliary atresia (3.3 +/- 0.2 years) (p < 0.01), but did not differ in terms of sex, ABO type, UNOS status or year in which the transplant procedure was performed. Interestingly, first allograft survival was equal in the children with neonatal hepatitis (74%) and those with metabolic liver disease (74%), but was greater than that for children transplanted for biliary atresia (68%) (p < 0.01). Despite this significant difference in first graft survival, no differences in 5-year survival were seen for the three groups (81% for neonatal hepatitis, 68% for biliary atresia and 79% for metabolic liver disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic hepatic encephalopathy is highly responsive to changes in diet, to antibiotic therapy and to ingestion of nondigestible disaccharides. The precise pathophysiology of chronic hepatic encephalopathy in individual cases is highly variable, although ammonia toxicity and production of neurotransmitterlike substances in the gut have been proposed to contribute to the overall syndrome of chronic hepatic encephalopathy. The support for this hypothesis is based on the empiric observation that reduction in protein intake, a catharsis or both are effective treatments for chronic hepatic encephalopathy. This study was performed to evaluate the effect of mild subclinical and low-grade (grade 0 to 1) chronic hepatic encephalopathy on gastric emptying and oral-cecal transit times. Thirty patients were studied. Ten had no evidence of chronic hepatic encephalopathy, as determined with a battery of neuropsychiatric studies (group 1); 10 had subclinical hepatic encephalopathy, as judged on the basis of abnormal neuropsychiatric test performance but normal neurological examination (group 2); and 10 had grade 1 hepatic encephalopathy. Each underwent a liquid gastric emptying study and a lactulose oral-cecal transit time study. No significant differences between groups were evident in the results of the gastric emptying studies. In contrast, the time required for a lactulose load to reach the cecum was significantly greater in the patients with hepatic encephalopathy (p < 0.01) and increased as a function of the hepatic encephalopathy grade.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To examine the efficacy of interferon therapy of hepatitis C in liver transplant recipients, to determine the effect of interferon on allograft rejection rates, and to examine the effect of the primary immunosuppressive agent (FK-506/cyclosporin) on the above. Design: A non-randomized consecutive patient treatment study. Patients: Fifty-two liver allograft recipients with hepatitis C virus (HCV) associated liver disease. All 52 patients had abnormal serum alanine aminotransferase (ALT) levels and in all, a liver biopsy confirmed the finding of post-transplant viral hepatitis.Interventions: All patients were treated with interferon at a dose of 5 million units three times weekly, administered subcutaneously for 6 months. Main outcome measures: Normalization of serum ALT levels was defined as a full response. A 50% reduction in serum ALT levels without normalization was defined as a partial response. Results: No difference in entry ALT levels or white blood cell counts was evident for the two groups based in the type of immunosuppression used, either cyclosporin or FK-506. Similarly, no difference in the response rate to interferon was observed based on the type of immunosuppression used. Improvement in ALT levels was not accompanied by a concomitant improvement in hepatic histology. Overall, Knodell scores for histology deteriorated in two-thirds of the patients despite interferon treatment. Conclusions: The use of interferon in liver transplant recipients reduces serum ALT levels but has little effect, if any, on hepatic allograft histopathology. In most patients, histology worsens despite interferon therapy. No difference in interferon response rates were observed between liver allograft recipients receiving either cyclosporin or FK-506.

The use of intraoperative endoscopy to localize a site of recurrent intestinal bleeding is reported wherein, once identified, the lesion was managed surgically without an enterostomy but with transluminal suture ligation. This technique is particularly attractive for use in debilitated or elderly patients and those with advanced decompensated liver disease complicated by portal hypertension.

The effects of liver transplantation and the obligate use of cyclosporine on the subsequent clinical course of nine patients with sarcoidosis were examined. Two comparison groups, each consisting o...

An overview is given of current practice in deciding which patients can undergo a major abdominal operative procedure involving the hepatobiliary system. The criteria developed for individuals with normal and diseased livers are presented, and the unique circumstances of liver transplantation are also addressed.

Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA-deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved.

Fulminant hepatitis a in patients with chronic liver disease- the importance of immunization revisited

Daily use of concensus interferon (CIFN) for the treatment of chronic hepatitis C infection: 1 year follow up results after 48 weeks treatment period