Cadaveric small bowel/split liver transplantation in a child

Scarcity of size-matched grafts continues to be a major limiting factor for liver and combined liver/intestinal transplants in the pediatric population. It is reported that 29 % of pediatric patients listed for hepatic transplantation die while waiting for a donor. The reported mortality of pediatric patients awaiting intestinal transplantation is about 40 %. We report on a technique of segmental liver and intestinal transplantation in a child. To our knowledge, this is the first report of a combined split liver-intestinal transplantation. We used a cadaveric donor, but the technique can also be performed with a live donor. The adult recipient of one segment of the liver was discharged home without complications. The child who received the combined liver intestinal graft developed intestinal perforation and severe rejection and died. If this technique is applied successfully, the adverse effects and mortality of a long pretransplant waiting period in pediatric patients may be avoided. Received: 7 May 1998 Received after revision: 29 September 1998 Accepted: 12 October 1998     

胆道闭锁婴儿亲属活体肝移植术后空肠穿孔四例

目的 分析胆道闭锁婴儿亲属活体肝移植术后空肠穿孔的原因,总结治疗经验.方法 胆道闭锁婴儿行亲属活体肝移植者28例,术后应用环孢素A、糖皮质激素预防排斥反应,部分患儿加用吗替麦考酚酯.结果28例中4例(14.3%)发生空肠穿孔,共发生7次,发生时间平均为术后11 d(8～13 d).4例的穿孔部位均在空肠,其中3例在肠吻合口丝线缝合线脚处,1例在肠袢臂固定丝线线头处.肠吻合口丝线缝合线脚处穿孔的3例经丝线缝合修补穿孔后,其中2例(67%)再次出现穿孔,用prolene线修补后愈合.无患儿因空肠穿孔而死亡.结论 胆道闭锁婴儿行亲属活体肝移植后发生空肠穿孔可能与用丝线吻合肠道有关,可换用Prolene线吻合肠道或修补穿孔.早期诊断和早期剖腹探查对空肠穿孔的治疗至关重要.

Abstract：

Objective To investigate the cause of jejunum perforation after infantile livingrelated liver transplantation (ILRLT) and summarize the experience of treatment. Methods The clinical data of 28 infants with biliary atresia who underwent ILRLT were analyzed and 4 of 28 infantile recipients (14. 3%) developed jejunum perforation after ILDLT. Results Four patients had 7 episodes of jejunum perforation after transplantation among 28 infantile recipients who underwent ILRLT because of biliary atresia. The median time between transplantation and perforation was 11 days.Perforation occurred at the point of silk in jejunum stoma (n = 3) and the Roux-en-Y limb (n = 1 ).None had a history of prior operation including Kasai in 4 patients. Clinical manifestation included fever, increased heart rate, abdominal distention, leukocytosis, and no free air on abdominal roentgenograrns. A simple repair was performed in three infants with silk: two developed recurrent perforation (67%) and underwent a re-exploration,and another had a third perforation and underwent a third repair because of re-perforation. Another child underwent a simple repair with prolene, and there was no recurrence. None died from the perforation in our study. Conclusion The occurrence and location of jejunum perforation after ILDLT suggests that the cause of the perforation is related to the jejunal anastomosis with silk, and the jejunum perforation may be avoided in the jejunal anastomosis with prolene. Early diagnosis and exploration may ensure better survival.     

Ureteral urine leak presenting as a pleural effusion in a renal transplant recipient

We report a 15-year-old girl who developed a ureteral perforation soon after living-related donor renal transplantation. Her presentation was unusual in that a symptomatic pleural effusion accumulated as an extension of the perinephric urine collection. Recognition and surgical correction of the ureteral pathology led to resolution of respiratory symptomatology and full recovery of renal function. Received October 15, 1997; received in revised form February 17, 1998; accepted February 20, 1998     

Splenic artery aneurysm and orthotopic liver transplantation

Splenic artery aneurysms are a rare but potentially fatal complication after liver transplantation. We report three cases presenting in a 12-month period in adult patients who underwent transplantation for chronic liver disease. Doppler ultrasound of the splenic artery should be performed in all patients with cirrhosis and portal hypertension who are being assessed for liver transplantation. The aneurysm can be ligated at the time of transplantation. Received: 28 April 1998 Received after revision: 31 July 1998 Accepted: 23 September 1998     

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver. Received: 15 September 1997 Received after revision: 4 February 1998 Accepted: 2 March 1998     

Disappearance of hepatitis B virus core deletion mutants and successful combined kidney/liver transplantation in a patient treated with lamivudine

Hepatitis B virus (HBV) core deletion variants with enhanced viral replication are associated with rapid deterioration of liver function in renal allograft recipients. Antiviral agents such as famciclovir and lamivudine offer new treatment strategies for these patients. Appearance, accumulation and persistence of HBV core deletion mutants were closely monitored in a kidney transplant recipient with liver cirrhosis before and after initiation of antiviral treatment. Under treatment with famciclovir HBV DNA concentration decreased by 50 %, HBV mutants persisted. After replacement of famciclovir by lamivudine HBV replication was reduced below the detection limit. Lamivudine was well tolerated and liver function improved. After successful combined kidney/liver transplantation the patient became HBsAg and HBV DNA (detected by PCR) negative under continuous hyperimmune globulin and lamivudine treatment. Antiviral therapy with lamivudine may be useful in treatment of progressive liver disease associated with HBV core deletion mutants in renal allograft recipients and may enable successful liver transplantation. Received: 12 June 1998 Received after revision: 16 October 1998 Accepted: 10 November 1998     

Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease

Sigmoid perforation due to diverticulitis is a life-threatening complication in the postoperative course of allogenic kidney transplantation. The incidence of diverticulosis is especially high among patients with autosomal dominant polycystic kidney disease (ADPKD). Thus, those who undergo allogenic kidney transplantation represent a high-risk group. The aim of this study was to evaluate the prevalence of diverticulosis in ADPKD patients awaiting renal transplantation and the incidence of bowel perforation following allogenic kidney transplantation due to ADPKD. Within the group of 1128 patients who underwent transplantation between January 1974 and January 1990, there were 46 patients (4.07 %) whose indication for transplantation was ADPKD. There was one patient who developed a sigmoid perforation under postoperative immunosuppression. Surgical treatment was a discontinuity resection of the sigmoid (Hartmann's procedure). The postoperative course was favorable, the bowel continuity has already been restored, and the graft is still functioning well. Fifteen of the 28 (53.5 %) ADPKD patients awaiting transplantation had colon diverticulosis (12 male and 3 female patients). No case of bowel perforation has thus far been observed in 15 of these patients who have undergone transplantation. A sigmoid resection was necessary in one patient due to diverticulitis without perforation. We did not find a higher prevalence of diverticulosis in patients with ADPKD, nor did we see a higher incidence of sigmoid perforation during post-transplant immunosuppression in this study. Received: 30 January 1997 Received after revision: 15 July 1997 Accepted: 19 August 1997     

Early acute cellular rejection: no effect on late hepatic allograft function in man

Whereas early acute cellular rejection, even if successfully treated, seems to have an impact on late function and survival of kidney and heart transplants, little quantitative data are available on its effect(s) on liver transplants. Routine liver function tests, the functioning liver cell mass (galactose elimination capacity) and microsomal metabolic capacity (aminopyrine breath test) were determined prospectively in 37 consecutive patients 1 year after liver transplantation. Of these, 19 (7 females and 12 males, 32–69 years of age) had previously required treatment for at least one biopsy proven acute cellular rejection episode occuring a median 7 days after grafting, while 18 (6 females and 12 males, 30–67 years of age) had not. The functioning liver cell mass and microsomal metabolic capacity were both within normal limits for the majority of patients and did not differ significantly between patients with and without previous acute cellular rejection episodes. In contrast to other solid organ transplants, early acute cellular rejection episodes do not affect late function of liver allografts in man. Received: 1 July 1998 Received in revised form 5 October 1999 Accepted: 12 October 1998     

Situs inversus of donor or recipient in liver transplantation

Situs inversus is a rare anatomical abnormality that is often associated with multiple, complex malformations. In the past, patients with situs inversus were considered unsuitable candidates for transplantation or organ donation because associated visceral, and especially vascular, anomalies pose special technical difficulties. Recently, several cases of successful liver transplantation in recipients with situs inversus have been published using modified surgical techniques. This report reviews the literature and describes our own experience, including two liver graft recipients with complete and incomplete situs inversus, and one patient who underwent successful transplantation using a liver from a donor with situs inversus. Received: 10 October 1997 Received after revision: 22 December 1997 Accepted: 9 January 1998     

Recurrent postinfantile syncytial giant cell hepatitis after orthotopic liver transplantation

Syncytial giant cell hepatitis is a severe form of hepatitis characterized by diffuse giant cell transformation of hepatocytes. The disease may evolve to chronic cholestatic cirrhosis necessitating liver transplantation. We report the case of an adult liver transplant recipient presenting with early recurrent disease without concomitant clinicobiochemical syndrome. Early recurrence of giant cell hepatitis after liver transplantation favors the hypothesis of a transmissible agent as the etiology of the disease. Routine follow-up liver biopsy is necessary in these cases in order to gain more information about the precise incidence and aggressivity of disease recurrence in the allograft. Received: 4 July 1997 Received after revision: 12 January 1998 Accepted: 11 February 1998     

肾移植术后并发肠穿孔的诊断和治疗体会

目的 总结肾移植术后并发肠穿孔的诊断和治疗体会.方法 回顾性分析8例肾移植术后并发生肠穿孔患者的资料.8例均为首次肾移植,术后采用环孢素A(或他克莫司)、霉酚酸酯及甲泼尼龙预防排斥反应.8例患者中,1例肾移植术前有胃大部切除手术史,其余7例术前无胃肠道病变.1例于肾移植术中切除了双侧多囊肾.1例在发生肠穿孔前因急性排斥反应而接受甲泼尼龙冲击治疗.8例患者均接受了剖腹探查术,同时减少免疫抑制剂的用量.结果 肠穿孔发生于肾移植术后3～18 d.5例患者表现为突发性腹部绞痛,不同程度的急性腹膜炎体征;3例急性腹膜炎体征不明显.患者体温为36.5～38.4℃.腹部X线检查显示,5例右侧或双侧膈下出现游离气体,3例出现肠管扩张及肠梗阻征象.诊断肠穿孔后3～96 h患者接受了剖腹探查.术中证实,7例为同肠穿孔,1例为降结肠穿孔.剖腹探查的同时,3例接受了小肠穿孔修补术,4例接受了部分小肠切除吻合术,1例接受了部分结肠切除吻合术.经手术治疗,5例患者痊愈出院.随访0.5～3.5年,肾功能良好,未再发生肠穿孔;3例患者分别于肾移植术后30～108 d因肠穿孔并发症死亡.结论 肠穿孔是肾移植术后少见而严重的并发症,其临床症状不典型,腹部X线检查结果对早期诊断具有较大意义,早期诊断和手术治疗是改善患者预后的关键.     

肝移植术后并发消化道穿孔六例报告

目的总结肝移植术后并发消化道穿孔的临床特点及诊疗体会。方法6例肝移植患者术后并发消化道穿孔,其中4例既往有腹部手术史。穿孔诊断时间在肝移植后7～12 d,确诊前2～4 d均有突发性腹部疼痛,但均能耐受,仅有1例腹痛较明显,上中腹压痛及反跳痛,其余5例腹肌不紧张,反跳痛不明显,6例均无明显的寒战及高热,5例的引流物细菌培养发现屎肠球菌感染,另1例未行引流物细菌培养。诊断明确后在全身麻醉下施行剖腹探查及穿孔修补术。结果3例(1例横结肠穿孔,1例胃壁、空肠穿孔,1例空肠憩室穿孔)穿孔直径较大,腹腔污染严重,手术过程中均出现感染性休克症状,分别于修补术后第2、9、33天死于多器官功能衰竭,另外3例(1例为回肠穿孔,1例为胃壁穿孔,1例为横结肠穿孔)的腹腔污染较轻,经穿孔修补术及营养支持治疗后痊愈。结论既往腹部手术史、医源性损伤及大剂量激素的应用,是导致肝移植后并发消化道穿孔的重要原因,而激素的应用使得患者的临床症状不明显,早期诊断、及时处理是治疗成功的关键。     

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation

A nested polymerase chain reaction (nPCR) for Epstein-Barr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30 % and RNA in 34 % of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods (P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90 % of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-immunoblastic infiltrates, either in nPCR (P = 0.73) or in ISH (P = 0.73). Two of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBV-nPCR but negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention. Received: 5 January 1998 Received after revision: 21 April 1998 Accepted: 20 May 1998     

Late onset cytomegalovirus disease in liver transplant recipients: de novo reactivation in recurrent hepatitis C virus hepatitis

Late onset cytomegalovirus (CMV) disease (occurring more than 1 year post-transplant] was documented in two liver transplant recipients with recurrent hepatitis C virus hepatitis in the absence of factors known to precipitate CMV disease, i. e., primary acquisition of CMV, allograft rejection, augmented immunosuppression, concomitant infections, or blood transfusions. Both patients had CMV enteritis (with CMV adrenalitis in one case]; however, other symptoms and signs of overt CMV infection, i. e., fever, leukopenia, or atypical lymphocytes, were lacking. Hepatitis C virus is an immunomodulatory virus; impaired CMV-specific T-cell responses may have accounted for the predisposition of our patients to unprovoked, late onset CMV disease. Given the high incidence of hepatitis C virus recurrence after liver transplantation, awareness of the occurrence and recognition of the unusual presentation of CMV disease in this setting is both clinically relevant and significant, particularly since CMV is treatable if recognized promptly. Received: 25 September 1997 Received after revision: 27 January 1998 Accepted: 2 March 1998     

High prevalence of pulmonary diffusion abnormalities without interstitial changes in long-term survivors of liver transplantation

Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20–147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0 % predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0 %), emphysematous bullae in 2/40 (5.0 %) and pleural thickening in 9/40 (22,5 %). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause. Received: 30 June 1998 Received after revision: 2 December 1998 Accepted: 7 January 1999     

Successful recanalization of late portal vein thrombosis after liver transplantation using systemic low-dose recombinant tissue plasminogen activator

Portal vein thrombosis (PVT) is an infrequent complication following hepatic transplantation. However, deterioration of liver function and accompanying complications may be life threatening. Several attempts of surgical or percutaneous transhepatic procedures have been described. In some cases high dose fibrinolytic regimens have been successful. We describe the case of a male liver recipient with recurrent liver fibrosis due to hepatitis B reinfection and late portal vein thrombosis 45 months after transplantation. Complete recanalization was achieved using systemic low dose recombinant tissue plasminogen activator (rt-PA). Received: 4 May 1998 Received after revision: 16 March 1999 Accepted: 9 April 1999     

Plasma proteolytic activity in liver transplant rejection

In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and α₂-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F 1 + 2), and plasmin/α₂-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Received: 20 January 1998 Received after revision: 11 September 1998 Accepted: 12 October 1998     

Mild chronic anemia following heart transplantation: a syndrome with prognostic relevance?

The clinical relevance of mild chronic anemia in patients after heart transplantation (HTX) has not yet been demonstrated. Forty-five outpatients who had undergone HTX 2–99 months prior to investigation and who had not received blood transfusions or erythropoietin (EPO) before data acquisition were observed over a period of 37 months. Anemia was found in 36 of the 45 patients and was normocytic, normochromic, and slightly anisocytotic (coefficient of variation = 16 ± 2, normal 11.5–14.5). Anemic patients showed elevated EPO levels, whereas in nonanemic patients EPO levels were normal. Survival after HTX differed significantly in anemic and nonanemic patients (P < 0.02), with 100 % survival in the nonanemic and 85 % in the anemic group. Chronic anemia in patients after HTX shows a typical pattern. Even when mild, anemia in patients after HTX seems to be of prognostic value and thus might be an indicator of chronic disorders. Received: 9 March 1998 Received after revision: 20 May 1998 Accepted: 26 June 1998     

Liver transplantation for primary sclerosing cholangitis

Although the development of interventional radiology and biliary surgical techniques has prolonged the survival time of patients with primary sclerosing cholangitis, liver transplantation remains the only effective treatment for patients with primary sclerosing cholangitis with liver cirrhosis. Several prognostic survival models have been establised for this disease, and the efficacy of actual liver transplantations has been reported in comparison with these survival models. One- and 5-year actuarial patient survivals after liver transplantation for primary sclerosing cholangitis were shown to be greater than and approximately equal to 90%, respectively. An association with cholangiocarcinoma is the most adverse factor affecting survival after liver transplantation for primary sclerosing cholangitis, while the association of inflammatory bowel disease or previous bili-ary surgery does not adversely affect the outcome of the liver transplantation. Recurrent sclerosing cholangitis is an important issue for posttransplant patients with primary sclerosing cholangitis, and occurs in 10%–20% of such patients. Although our understanding of recurrent sclerosing cholangitis is still in the early stages, its potential occurrence indicates the need for a longer follow-up period after liver transplantation. Received for publication on April 30, 1999; accepted on April 30, 1999     

Transmission of factor VII deficiency through liver transplantation

The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency. In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications. Received: 6 November 1998 Received after revision: 26 April 1999 Accepted: 4 May 1999