Harlan I. Wright

Response to interferon α therapy is influenced by the iron content of the liver

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 α therapy. Each subject was treated for 6 months with interferon α . 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 μ g/g dry weight vs. 638±118; p

Intestinal transplantation in composite visceral grafts or alone.

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.

Liver biopsy : its safety and complications as seen at a liver transplant center

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 recipients immunosuppression regimen or gauge the response to a recent change in immunosuppression. At the University of Pittsburgh Medical Center, adult liver transplant patients have been biopsied using 3 different techniques based upon the physicians (Tru-cut needle) or surgeons (suction needle) personal choice and whether or not it has been the intent of the biopsy to obtain tissue from a focal lesion within a liver. In the latter cases, ultrasound guidance and an automated biopsy needle are used. In the former, either a suction-type needle (Jamshidi) or a cutting needle (Tru-cut) has been used. During the period between January 1, 1989, and December 31, 1991, a total of 12,750 liver biopsies have been done on patients admitted to the adult transplant service at this institution. Of these, 8500 were performed with a suction needle, 4195 were performed using a cutting needle, and 55 were performed under ultrasound guidance using an automated cutting needle. A total of 26 major complications occurred--19 with the suction needle (0.22%); 6 with the cutting needle (0.14%), and 2 using ultrasound guidance and an automatic cutting needle (3.6%). Nine of these 26 complications required surgical intervention consisting of a thoracotomy or laparotomy; 4 required the insertion of a chest tube and two required hepatic artery embolization. Based upon these data obtained at a large transplant center, it can be concluded that, in general: (1) a liver biopsy can be done safely in liver transplant recipients; (2) an overall low rate of major complications occurs varying from 0.1 to 3.6% depending upon the type of needle and other circumstances relating to the biopsy procedure; (3) complications, when they occur, are morbid and often necessitate either additional surgical or interventional radiologic procedures.

Clinical Course after Liver Transplantation in Patients with Sarcoidosis

Sarcoidosis is a disease of unknown cause that primarily involves the lungs and lymph nodes but is known also to involve the skin, liver, lacrimal glands, and potentially any organ or tissue in the body [1]. The disease is characterized by the presence of noncaseating granuloma consisting of epithelioid cells and activated CD4+ T cells. Sarcoidosis can cause liver disease as well as hepatosplenomegaly, presinusoidal portal hypertension, and, rarely, a diffuse intrahepatic biliary disease similar to that seen in patients with primary sclerosing cholangitis [2]. In addition to being a cause of liver disease, sarcoidosis often coexists with other well-recognized liver diseases, such as primary biliary cirrhosis, alcoholic liver disease, and postnecrotic cirrhosis due to either chronic hepatitis B or hepatitis C virus infection. In either setting, patients with sarcoidosis become candidates for liver transplantation as a consequence of end-stage liver disease. By necessity, liver transplantation is followed by a lifelong requirement for immunosuppressive therapy to prevent allograft rejection [3]. Immunosuppression is used also as primary treatment for patients with advanced symptomatic sarcoidosis and for those with disease involving the pulmonary parenchyma, myocardial conduction system, eyes, and central nervous system. Studies suggest that such therapy is efficacious and prolongs life as well as organ function [4-9]. The effects of liver transplantation and the subsequent use of cyclosporine in patients with sarcoidosis have not been reported previously. We report our experience with liver transplantation in 9 patients with sarcoidosis and in 36 recipients without sarcoidosis (18 with cholestatic liver disease and 18 with hepatocellular disease) who were matched for age, gender, and time of liver transplantation. Methods Patients From 1 January 1981 through 31 December 1991, nine adult patients with a diagnosis of sarcoidosis and with or without another cause of liver disease underwent orthotopic liver transplantation at the University of Pittsburgh. Their mean age was 45.1 2.8 years. Four were male and five were female. Their mean UNOS (United Network for Organ Sharing) score at the time of liver transplantation was 2.8 0.3. For each liver transplant recipient with sarcoidosis that was identified, four liver transplant recipients without sarcoidosis were identified who had undergone transplantation within 30 days of the patient with sarcoidosis: In each case, two of the patients underwent transplantation because of a parenchymal (hepatocellular) liver disease (mean age, 45.3 1.9 years; UNOS score, 3.1 0.2), and two underwent transplantation because of a cholestatic liver disease (mean age, 43.8 2.0 years; UNOS score, 2.7 0.2). Chart Review The medical and surgical records of the nine patients with sarcoidosis were reviewed to determine the tissue sites of sarcoid involvement, the course of sarcoidosis after liver transplantation, and the post-transplant course and prognosis as assessed by serial angiotensin-converting enzyme levels, pulmonary function tests, and chest radiographs. Statistical Analysis Life-table analysis for patient and graft survival was carried out using the methods of Kaplan and Meier [10]. The differences in survival between the patients with sarcoidosis and the two comparison groups were analyzed [10]. Results The 9 patients with sarcoidosis, the 18 patients with cholestatic liver disease (8 with primary sclerosing cholangitis and 10 with primary biliary cirrhosis), and the 18 patients with parenchymal liver disease (8 with viral hepatitis, 8 with alcoholic liver disease, and 2 with cryptogenic liver disease) had similar demographic characteristics. None of the patients with parenchymal liver disease had hepatitis B, but eight did have hepatitis C. Total bilirubin levels in the sarcoidosis, cholestatic disease, and parenchymal disease groups were 133.4 25.7 mol/L, 295.8 37.6 mol/L, and 35.9 5.1 mol/L, respectively; albumin levels were 27 4 g/L, 33 2 g/L, and 23 4 g/L, respectively; and prothrombin times were 15.1 0.2 s, 13.1 0.2 s, and 17.3 0.2 s, respectively. In each instance, liver function measurements for the sarcoidosis group fell midway between the measurements for the two comparison groups. In patients with sarcoidosis, tissue involvement was demonstrated histopathologically. All nine patients had hepatic involvement; seven had pulmonary and mediastinal node involvement; three had lacrimal gland and skin involvement; and three had upper airway disease. The serum angiotensin-converting enzyme level and the peripheral blood helper (CD4+)/suppressor (CD8+) cell ratio were determined before liver transplantation in all nine patients with sarcoidosis: The patients had an elevated angiotensin-converting enzyme level (mean, 136 11 U) and a CD4+/CD8+ ratio of 1.9 0.2. All nine patients received cyclosporine. Graft and patient survival in the three groups is shown in Figure 1. No statistical difference between the three groups for either graft or patient survival was evident through 76 months (6.3 years). Although not significant, patient survival in the sarcoidosis group was arithmetically better through the first 5 years than that in the two comparison groups. The three deaths that occurred in the sarcoidosis group at 6 years were caused by metastatic hepatocellular cancer; recurrent non-A, non-B hepatitis; and cryptogenic cirrhosis. Figure 1. Patient and graft survival in the three study groups. The most recent laboratory test results for the survivors in each group were normal. No evidence of disease progression or continued disease activity was seen. The hepatic disease in each case was eliminated by the total hepatectomy required as part of the liver transplant procedure. The lack of disease progression or continued disease activity involving the lungs, skin, and lacrimal glands reflects the intensity of the immunosuppressive therapy. Discussion Our retrospective study showed that patients with sarcoidosis who receive a liver allograft and are required to take immunosuppressive agents at doses that prevent allograft rejection experience a remission of their sarcoidosis. These data confirm the beneficial efforts of cyclosporine in patients with clinically active sarcoidosis and those with disease involving critical organs [6-10]. Our results, when combined with those from earlier series of patients with sarcoidosis who did not receive an organ allograft, define the dose range within which patients with active sarcoidosis can be treated and their disease controlled completely without producing unacceptable drug-associated toxicities. Such information is particularly important in patients with sarcoidosis, who may require prolonged immunosuppressive therapy.

Continuous Intraarterial Thrombolysis for Early Hepatic Artery Thrombosis Following Liver Transplantation: Case Report

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).

Treatment of IgA deficiency in liver transplant recipients with human breast milk

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. Mothers 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.

Types, causes, and therapies of hepatitis occurring in liver transplant recipients

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.

Alpha-interferon treatment of hepatitis C in patients with liver allografts treated with either FK-506 or cyclosporin A

Objectives: 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.

Transluminal ligation of bleeding angiodysplasia of the small bowel without need for surgical resection

SummaryThe 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.

Effect of capsule on surface diffuse refelectance spectroscopy of capsular solid organs (Conference Presentation)

Surface diffuse reflectance spectroscopy (DRS) has the potential for real-time, bed-side evaluation of solid donor organs including liver and kidney for transplant. Nilsson et al used an applicator-probe with multiple source-detector paired with a 2.5mm source-detector separation to show that DRS of liver through the capsule represents the DRS of cross-sectional liver; however, a small but consistent difference over 600nm—850nm between DRS with capsule and without capsule was observed. Understanding the effect of the capsule on surface DRS of solid capsular organs is important to accurately resolving subcapsular tissue properties for the evaluation of organ quality. We have developed a portable lab-on-a-crater DRS system with an applicator-probe with 3mm source-detector separation for evaluating human liver and kidney specimens routinely in a pathology lab. The DRS performed on liver with capsule is consistently lower in the spectral intensity between 600-850nm when compared to DRS performed on the cross-section of liver, regardless of the pathology of subcapsular parenchyma. To model the effect of capsule on surface DRS of capsular solid organs like liver, we have implemented an analytical approach based on a master-slave dual-source configuration model (Piao and Patel, App. Opt, 56(5) 1447-1452, 2017). Under the assumption of the capsular layer having lower oxygenated hemoglobin and potentially increased elastin content and by making the location and intensity of the slave-source dependent upon the properties of the capsular layer, the surface DRS predicted by this master-slave dual-source model reveals the measured pattern over 600-850nm between with the capsule and without the capsule.