Changing perspectives on liver transplantation in 1988.

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation

Diminishing Use of Liver Biopsy among Liver Transplant Recipients for Hepatitis C.

Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation

Orthotopic liver transplantation in children. Two-year experience with 47 patients

During a 24-month period (May 1981 to May 1983), 47 pediatric patients (ranging in age from 7 months to 18 years) underwent orthotopic liver transplantation using cyclosporine and prednisone. Major indications were biliary atresia/hypoplasia, and metabolic liver disease. Thirty-two of 138 patients evaluated for the procedure died prior to transplantation. Thirty patients are alive from 6 to 29 months later including 7/15 patients who required retransplantation. Twenty-one of 32 patients are alive at 1 year following initial transplantation. All 30 survivors are clinically well and living at home; only one has an abnormal bilirubin level. Serious, life-threatening medical and surgical complications were common during the early months following transplantation. With one exception, deaths and major rejection episodes occurred early (before 120 days). All survivors are relieved of the stigmata of chronic liver disease, and many have demonstrated catch-up growth. Liver transplantation is an effective treatment for end-stage pediatric liver disease

Pancreatic hormones and amino acid levels following liver transplantation

Glucose intolerance, hyperinsulinemia, peripheral insulin resistance and hyperglucagonemia are common in patients with advanced liver disease. These abnormalities in the plasma levels of the pancreatic hormones, insulin and glucagon have been thought to be responsible, at least in part, for the abnormal plasma ratio of branched‐chain amino acids to aromatic amino acids. To evaluate this issue, plasma levels of glucose, insulin, glucagon, C‐peptide and the branched‐chain and aromatic amino acids were measured before and serially after orthotopic liver transplantation in 9 humans and 5 dogs. The abnormal plasma amino acid levels rapidly improved and achieved normal levels following orthotopic liver transplantation. Insulin levels also became normal following orthotopic liver transplantation, despite enhanced insulin secretion documented by an even further increased level of C‐peptide. In contrast, the baseline abnormal plasma glucagon levels which are commonly seen in cirrhotics became even more abnormal following orthotopic liver transplantation. Despite this progressive increase in the abnormally elevated plasma glucagon levels, plasma amino acid levels, both branched‐chain and aromatic, became normal. These data demonstrate that before and after orthotopic liver transplantation, there is: (i) no relationship between the changes in plasma levels of glucagon and changes observed in the plasma level of amino acids; and (ii) plasma insulin and amino acid levels change in the same direction. In addition, these changes in plasma insulin and amino acid levels following orthotopic liver transplantation occur despite enhanced secretion of insulin evidenced by the progressive increase in plasma levels of C‐peptide. Copyright © 1987 American Association for the Study of Liver Disease

Indwelling Pleural Catheters in Hepatic Hydrothorax: A Single-Center Series of Outcomes and Complications

Background Treatment of hepatic hydrothorax (HH) generally involves sodium restriction, diuretics, and serial thoracentesis. In more advanced cases, transjugular intrahepatic portosystemic shunt and liver transplantation may be required. Previously, indwelling tube drainage has been avoided due to concerns regarding high complication rates and overall poor outcomes. Recently, indwelling pleural catheters (IPCs) have been proposed as a novel treatment option for HH. Methods This study was a retrospective review of patients who had undergone IPC placement for HH over a 10-year period at a large liver transplant referral center. We tracked outcomes, including complication rates and liver transplantation, as well as biomarkers of nutritional status. Results Sixty-two patients underwent IPC placement between 2007 and 2017, with 33 IPCs (53%) placed as a bridge to liver transplantation. Complications were recorded in 22 patients (36%); empyema was the most common, diagnosed in 10 patients (16.1%). Ten patients evaluated for liver transplantation underwent successful transplantation following IPC placement. There were statistically significant decreases in both BMI and serum albumin levels following IPC placement. Conclusions IPCs represent a potential treatment for refractory HH and should be used with caution in patients eligible for liver transplantation. Ideally, IPC use for these patients would be evaluated by a multidisciplinary team. IPC use may lead to small decreases in BMI and serum albumin levels in patients over time

Acute pancreatitis after liver transplantation: incidence and contributing factors

In order to assess the incidence and possible predisposing and contributing factors in the development of acute pancreatitis after liver transplantation, we reviewed the medical records of all 1832 adult patients who underwent 2161 orthotopic liver transplantation (OLTx) procedures in our center between January 1987 and September 1992. Of these patients, 55 (3 % incidence) developed clinical pancreatitis and 247 (13.4 % incidence) developed hyperamylasemia (biochemical pancreatitis). Overall mortality in cases of clinical pancreatitis was 63.6 %. The mortality in cases of hyperamylasemia was similar to that found in the general liver transplant population (i. e., 23 %). A strong correlation was found between pancreatitis after liver transplantation and end-stage liver disease due to hepatitis B (30 % of the cases, P = 0.00001). Extensive surgical dissection around the pancreas (P < 0.05), the type of biliary reconstruction following liver transplantation (P < 0.05), and the number of liver grafts received by the same patient (P = 0.00001) appeared to be possible contributing factors as did the duration of venovenous bypass and the quantity of IV calcium chloride administered intraoperatively

Liver transplantation: an unfinished product.

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies

Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis

Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty‐seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow‐up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.(HEPATOLOGY 1990;11:477–480.) Copyright © 1990 American Association for the Study of Liver Disease

Orthotopic liver transplantation for fulminant and subacute hepatic failure

Fulminant and subacute hepatitis are conditions characterized by rapid liver failure, which can lead to death in 80 to more than 95% of the cases with medical supportive care only. The etiology can be viral, drug-, or other chemical-induced, metabolic, etc. Orthotopic liver transplantation emerged during the 1980s as a powerful means for dealing with these diseases. The existence of this therapeutic modality has brought about major changes in the diagnosis, patient selection, treatment, and outlook for fulminant/subacute liver failure. The authors present the results of orthotopic liver transplantation for the treatment of 47 cases of acute/subacute hepatic insufficiency at the University of Pittsburgh between March 1980 and July 1987. The results of this series demonstrate that liver transplantation is the most effective means for treating this condition

Isohemagglutinins of Graft Origin after ABO-Unmatched Liver Transplantation

THE increasing success of liver transplantation in recent years has provided an experimental model to study and document the hepatic synthesis of many plasma proteins.12345 The normal hepatobiliary tract has not been regarded as a major source of antibody,6,7 aside from the enteric IgA secreted from plasma into the biliary tree.8 Liver transplantation affords the opportunity to study the production of antibody to red cells. Recipient ABO incompatibility to the donor (a mismatched transplant, e.g., a group A liver transplanted into a group B recipient), although not absolutely contraindicated in liver transplantation, is avoided when possible. However, ABO-unmatched transplants (defined. © 1984, Massachusetts Medical Society. All rights reserved