Recurrent hepatitis C after liver transplantation: a nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin.

Liver transplant recipients with recurrent hepatitis C virus (HCV) infection often have histological hepatitis, and in some patients, graft failure develops. The aim of this nonrandomized study is to determine the efficacy and tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavirin combination therapy in such patients. Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times weekly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary end points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy. End-of-treatment biochemical responses were similar in the two groups (IFN alfa, 20% v combination therapy, 25%); however, viral clearance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IFN-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantly in both groups during therapy. There was no improvement in inflammatory grade, and fibrosis score was worse in both groups. Ten patients (25%) in the IFN-alfa group and 5 patients (20%) in the combination-therapy group withdrew because of adverse effects. We conclude that in liver allograft recipients with recurrent hepatitis C, combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability.

Internal hernia: clinical and imaging findings in 17 patients with emphasis on CT criteria.

PURPOSE: To review the clinical and radiologic features of internal hernia and to derive useful radiographic and CT criteria to assist in diagnosis. MATERIALS AND METHODS: Retrospective review of medical records revealed 17 patients with surgically proved internal hernia (three paraduodenal, 14 transmesenteric) who had 15 computed tomographic (CT) scans and three small-bowel follow-through (SBFT) images. RESULTS: CT signs common to all types of internal hernia included evidence of small-bowel obstruction; clustering of small bowel; stretched, displaced, crowded, and engorged mesenteric vessels; and displacement of other bowel segments, especially the transverse colon and fourth portion of the duodenum. Left-sided paraduodenal hernias demonstrated a sac-like mass of small-bowel loops interposed between the stomach and pancreatic tail and a posterior mass effect on the stomach. All three paraduodenal hernias were diagnosed confidently at retrospective review of CT and SBFT findings. Transmesenteric hernias demonstrated clustered small-bowel loops adjacent to the abdominal wall without overlying omental fat and central displacement of colon and were frequently complicated by small-bowel volvulus (five of 14) and bowel ischemia (six of 14). CT demonstrated signs of volvulus in four of six patients with ischemia. CT findings considered definitive or suggestive of internal hernia were demonstrated in 15 patients. CONCLUSION: Internal hernia is an important and underdiagnosed condition. Transmesenteric hernia is most common in our experience and is usually related to prior abdominal surgery, especially with creation of a Roux-en-Y anastomosis. CT may allow confident diagnosis in most patients.

Long-term survival after liver transplantation in 4,000 consecutive patients at a single center.

OBJECTIVE: To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation. METHODS: Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined. RESULTS: The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss. CONCLUSION: Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.

Prevention of de novo hepatitis B infection after liver transplantation with allografts from hepatitis B core antibody positive donors.

The frequent scarcity of organ donors has made it necessary to consider transplantation of organs that may have the potential to transmit hepatitis B virus (HBV) to the recipient. Previous reports have documented the probability of infection of particular recipient populations with transplanted livers from hepatitis B core antibody (anti-HBc) positive donors. Results have varied depending on the status of the recipients with respect to antibodies directed at the virus. Anti-HBc-positive and anti-HBs-positive recipients were generally resistant to hepatitis B infection, with the former infected at a low rate and the latter not at all. However, the probability of de novo HBV infection in naive recipients (anti-HBc-negative and anti-HBs-negative) was quite high (about 70%). The survival rate for infected patients is similar to those who are uninfected, but a significant percentage of infected patients will develop chronic hepatitis and a small percentage will develop allograft failure. Also reported here is a protocol designed to prevent the adverse consequences to naive recipients receiving livers from anti-HBc-positive donors. Hepatitis B immunoglobulin (HBIg) and lamivudine were utilized to prevent transmission of the hepatitis B virus. This combination has prevented de novo infections in all patients tested thus far. There are indications that HBIg or lamivudine may not be as effective when administered separately.

Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis B recurrence after liver transplantation.

The prevention of recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) with hepatitis B immunoglobulin (HBIG) is expensive and requires indefinite parenteral administration. Lamivudine is a nucleoside analogue capable of inhibiting HBV replication. The aim of this study is to determine the efficacy of lamivudine in the prevention of recurrent HBV infection after a course of HBIG in patients who were hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBeAg) negative before OLT. Patients at high risk for recurrent HBV infection (HBeAg positive and HBV DNA positive) were excluded. Thirty HBsAg-positive, HBeAg-negative patients underwent OLT from January 1993 to June 1997. All 30 patients were administered HBIG after OLT and, after 2 years, were given the option of continuing with HBIG or switching to lamivudine. Five patients were excluded: 3 patients were lost to follow-up and 2 patients died of technical complications. Three patients terminated HBIG therapy at 8, 24, and 29 months after OLT, and reinfection with HBV occurred in 1 patient. Six patients elected to continue HBIG therapy for life; 1 patient died of melanoma and the remaining 5 patients are HBsAg negative, with an average follow-up of 73 months. Sixteen patients were converted to lamivudine after a course of HBIG, and all 16 patients are HBsAg negative, with an average follow-up of 51 months after OLT. Five patients have been on lamivudine monotherapy for more than 24 months. These results suggest that lamivudine administered after a posttransplantation course of HBIG can effectively prevent the recurrence of HBV infection in patients who are HBsAg positive and HBeAg negative before OLT.

Clinical and virologic outcomes of hepatitis B and C viral coinfection after liver transplantation: effect of viral hepatitis D.

Hepatitis B (HBV) and C viral (HCV) dual-infection-associated liver disease is an uncommon indication for liver transplantation. The clinical and virologic outcomes in such patients have not been well studied. We retrospectively studied 13 patients with hepatitis B surface antigen (HBsAg) and antibody to HCV positivity who underwent orthotopic liver transplantation (OLT) and survived at least 30 days post-OLT. Antibody to hepatitis delta virus (HDV) was negative in 8 patients (group I) and positive in 5 patients (group II). Eleven of the 13 patients received standard hepatitis B immune prophylaxis, and they all remained HBsAg negative. All group I patients were HCV RNA positive after transplantation; in contrast, all group II patients were HCV RNA negative. Serum alanine aminotransferase levels were elevated in 88% (7 of 8) of the patients in group I compared with 20% (1 of 5 patients) in group II. None of the patients had graft loss from chronic rejection or recurrent hepatitis. Three patients had unsuspected hepatocellular carcinoma in the explant. We conclude that among liver transplant recipients with HBV and HCV coinfection, HDV infection is associated with the suppression of HCV replication and mild inflammatory activity after OLT.

Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors.

BACKGROUND: The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc+ donors in recipients who are susceptible to de novo hepatitis B virus (HBV) infection. The efficacy of hepatitis B immune globulin and lamivudine to prevent de novo HBV infection in anti-HBs negative recipients of allografts from anti-HBc+ donors has not been investigated. METHODS: After liver transplantation with an allograft from a donor positive for anti-HBc, recipients who were anti-HBs-, HbsAg- received hepatitis B immune globulin (HBIG) 10,000 IU i.v. daily for 7 days and monthly for 6 months. After 6 months, 1000 IU of HBIG was given IM. every 2 weeks for 18 months. Patients transplanted after 4/1/97 were given lamivudine 150 mg daily starting postoperative day 1. RESULTS: Between 8/14/96 and 6/10/98, 264 orthotopic liver transplants were performed and 16 anti-HBs-, HbsAg- patients received an hepatic allograft from a donor positive for anti-HBc. HBIG mono-therapy was administered to one patient. HBIG and lamivudine combination therapy was administered to 15 patients. Of the 16 patients, 8 were positive only for anti-HBc before transplant, and 8 were naive (anti-HBs-, anti-HBc-). The single patient who received HBIG monotherapy became HbsAg+ at 6 months. All patients receiving combination therapy with HBIG and lamivudine have remained HbsAg-. The average follow-up is 459 days (range 170-754). Two patients died from unrelated causes. CONCLUSIONS: Combination therapy with HBIG and lamivudine may prevent de novo HBV infection in anti-HBs-, HbsAg- recipients of hepatic allografts from anti-HBc+ donors.

The hepatopulmonary syndrome.

The hepatopulmonary syndrome is a disease entity seen in association with liver failure and other disease entities. It is a devastating consequence of liver failure that results in a significant morbidity for affected patients. Currently, there are no identified medications that ameliorate the symptoms of hypoxemia in this disease state. Recent research, however, has begun to unravel the pathobiology of the vascular dilations that arise in the lungs of patients with liver failure. In this article, a compendium of current knowledge is presented, as well as the contemporary methods for identifying and treating patients.

Liver transplantation for chronic viral hepatitis.

A better understanding of the mechanism of viral replication and of viral transmission has led to improved results with OLTx for patients with end-stage liver disease caused by viral hepatitis. Patients with hepatitis-B-related liver disease who are HBV-DNA negative can expect excellent survival after OLTx with long-term HBIG therapy. Patients coinfected with HDV who are HBV-DNA negative can also expect an excellent rate of survival. HBV-DNA-positive patients may benefit from the addition of lamivudine to the prophylactic regimen both before and after OLTx. De novo HBV infections generally have a very benign course. Lamivudine has proven to be very effective in the treatment of both de novo and recurrent HBV infection after OLTx; however, resistance can develop. Allografts from donors with antibodies to HBV can be used most effectively when directed to recipients who also harbor HBV antibodies. The recurrence of HCV infection after OLTx is universal; however, the 5-year survival rate in patients who received OLTx for HCV-related liver disease is not diminished. Although a few patients experience an aggressive recurrence of HCV infection after OLTx, prognostic indicators have not been determined to allow for identification of these patients. Alpha-interferon does not seem to be effective in the treatment of recurrent HCV infection after OLTx. Trials with combination alpha-interferon-ribavirin are underway. Retransplantation for HCV-related allograft failure can be performed safely in patients if performed before the onset of other organ system failure. Finally, anti-HCV-positive recipients of allografts from anti-HCV-positive donors have an excellent 5-year survival rate.

Strategies to expand the donor pool for pancreas transplantation.

BACKGROUND: Our organ procurement organization has been forced to liberalize the donor criteria in order to expand the donor pool for pancreas transplantation. In this report, we describe our experience using whole organ pancreatic grafts from "marginal" donors, which include grafts obtained from donors over 45 years of age and from donors who were identified to be hemodynamically unstable at the time of organ retrieval. METHODS: A prospective study was performed between July 1994 and March 1998, during which time 137 pancreas transplants were performed at our center using organs procured by our own surgeons (organs sent by other teams were excluded). The rapid en bloc technique was used exclusively. The use of pancreatic grafts from marginal donors was analyzed for short-term and overall graft survival, and for delayed graft function and complications. RESULTS: Overall pancreas graft survival for our series was 83%, with a mean follow-up of 23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of whom were greater than 50 years of age. The actual graft survival rate of the over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically unstable donors on high-dose vasopressors. The actual graft survival in this group was 86%. There was no significant difference found in graft survival between recipients of pancreatic grafts from marginal and nonmarginal donors. Delayed graft function was exhibited by more recipients of grafts from donors on high-dose vasopressors (P<0.05), but this had no effect on long-term graft survival and endocrine function. Recipients of marginal donor grafts did not have higher rates of complication compared to recipients of nonmarginal grafts. CONCLUSIONS: Based on our results, we currently employ a graft selection strategy not limited by donor age or hemodynamic stability. Our selection of pancreas organs for transplantation is based on careful inspection of the pancreas and determination of the adequacy of the ex vivo flush. Our results suggest that the current pancreas donor pool may be expanded substantially.

Tacrolimus without antilymphocyte induction therapy prevents pancreas loss from rejection in 123 consecutive patients.

In this series, antilymphoid induction therapy did not appear to be necessary to prevent early graft loss from rejection. In addition, we have followed cytomegalovirus (CMV) antigenemia (pp65) for CMV infection. Although some patients developed a positive antigenemia in the seropositive to negative donor-recipient combinations, only one patient had a prolonged febrile course for 1 week.

Infectivity of hepatic allografts with antibodies to hepatitis B virus.

BACKGROUND: Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS: Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS: From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS: Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.

Corrective treatment and anatomic considerations for laparoscopic cholecystectomy injuries.

BACKGROUND: Complete reports of biliary and vascular injuries after laparoscopic cholecystectomy are rare. STUDY DESIGN: Fifteen patients with complex laparoscopic cholecystectomy injuries underwent corrective operations. The injuries consisted of 14 bile duct injuries and one large laceration of a cirrhotic liver. Five of the bile duct injuries were accompanied by inadvertent occlusion of the right hepatic artery, and one was further complicated by portal vein occlusion. One hepatic artery occlusion and one portal vein occlusion were successfully reconstructed. Two patients with arterial occlusion required right hepatic lobectomy. Corrective biliary operations consisted of common hepaticojejunostomy (seven cases), right and left hepaticojejunostomies (one case), right anterior and left hepaticojejunostomies (two cases), right hepaticojejunostomy (one case), right posterior hepaticojejunostomy (one case), and left hepaticojejunostomy after right lobectomy (two cases). RESULTS: Except for a patient with a severe laceration of a cirrhotic liver who died as a result of hepatic failure, the remaining 14 patients are alive and well with normal hepatic function tests at six and 37 months after corrective operations. CONCLUSIONS: A knowledge of anatomy is critical to the prevention of injuries to the hepatobiliary tree and related structures during laparoscopic cholecystectomy.