Nodular regenerative hyperplasia: a controversial indication for orthotopic liver transplantation

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.     

Results of liver transplantation for nodular regenerative hyperplasia

Liver transplantation has been performed in individuals with a pretransplant clinical diagnosis of cirrhosis but with nodular regenerative hyperplasia histologically. The purpose of this report is to investigate the results of liver transplantation in patients proven to have nodular regenerative hyperplasia post-transplant. A retrospective review was undertaken of four patients who underwent liver transplantation with a histologic diagnosis of nodular regenerative hyperplasia. All were felt to be cirrhotic on clinical grounds. Final histology of the explanted liver was confirmed by a single pathologist. Their ages ranged from 39 to 54 years, and three of the four were male. Three had pretransplant needle liver biopsies, two percutaneous and one transjugular. All revealed nonspecific reactive changes. Ultrasound and MRI were interpreted as consistent with cirrhosis in four of four and three of four cases, respectively. Portal vein flow was hepatopedal in three and absent in one. Pretransplant clinical characteristics and frequency were as follows: bleeding varices two, clinical ascites three, encephalopathy three, and impaired hepatic synthetic function two. All four patients underwent successful liver transplantation. There were no episodes of acute rejection. All are alive and well with normal graft function 2 to 4 years post-transplant. We conclude the following. 1) Patients with clinical end-stage liver disease due to underlying nodular regenerative hyperplasia can successfully undergo transplantation. 2) Nodular regenerative hyperplasia can present with signs and symptoms of liver failure, is difficult to diagnose by needle biopsy, and can be difficult to discriminate clinically from cirrhosis. 3) Although each case must be individually evaluated transplantation may be the optimal therapy in patients presenting with complications of liver failure.     

肝海绵状血管瘤合并结节性再生性增生误诊为肝癌合并肝硬化1例报告并文献复习

背景与目的：肝海绵状血管瘤是最常见的肝脏原发肿瘤。尽管通过影像学检查,针对该病的诊断程序已经非常成熟,但在罕见疾病组合的情形中仍有被误诊为肝细胞癌的风险。本文通过回顾1例术后被诊断为海绵状血管瘤合并结节性再生性增生的肝移植病例,分析诊疗过程中的关键疑难点,复习海绵状血管瘤和结节性再生性增生的临床病理特征以及其与肝细胞癌和肝硬化的鉴别要点,旨为今后临床工作提供经验与教训。方法：回顾性分析武汉大学中南医院收治的1例肝移植患者的临床病史资料、影像学特点及病理组织学诊断,结合国内外文献中肝海绵状血管瘤和结节性再生性增生的特点,对本病例诊疗过程进行分析和归纳。结果：患者,男性,71岁,因腹水及肝右叶占位性病变入院。影像学检查提示肝硬化、腹水及肝右叶占位性病变。全腹部CT平扫和增强诊断肝硬化合并肝细胞癌。经全科会诊与患者充分沟通后,患者进行了肝移植术。术中检查和术后大体检查发现肝脏呈弥漫结节性改变伴肝右叶占位性病变。组织学发现前者为结节性再生性增生,而占位性病变则为海绵状血管瘤。结论：通常情况下肝海绵状血管瘤不存在影像学诊断困难,但在弥漫结节性背景下,海绵状血管瘤仍可被误诊为肝细胞癌。结节性再生性...     

Portal revascularization in the setting of cavernous transformation through a paracholedocal vein: a case report

Diffuse thrombosis of the entire portal system (PVT) and cavernomatous transformation of the portal vein (CTPV) represents a demanding challenge in liver transplantation. We present the case of a patient with nodular regenerative hyperplasia and recurrent episodes of type B hepatic encephalopathy concomitant with PVT as well as CTPV, successfully treated with orthotopic liver transplantation. The portal inflow to the graft was carried out through the confluence of 2 thin paracholedochal varicose veins, obtaining good early graft function and recovery of the encephalopatic episodes. This alternative should be kept in mind as an option to assure hepatopetal splanchnic flow in those cases of diffuse thrombosis and cavernomatous transformation of portal vein.     

Liver transplantation for hepatopulmonary syndrome due to noncirrhotic portal hypertension

Background

Hepatopulmomary syndrome is defined by the triad of chronic liver disease, increased alveolar-arterial gradient, and evidence of intrapulmonary vasodilation. It is commonly seen in association with cirrhosis (90%). Four percent to 8% of the hepatopulmomary syndrome cases are reported in noncirrhotic portal hypertension. The management of patients with hepatopulmomary syndrome due to noncirrhotic portal hypertension is not well described.

Methods

We report a case of a 26-year-old woman who underwent liver transplantation for hepatopulmomary syndrome due to noncirrhotic portal hypertension. The patient presented with dyspnea and platypnea, requiring home oxygen therapy. She had orthodexia, severe hypoxemia, and positive bubble echocardiography consistent with hepatopulmomary syndrome. Her Model for End-stage Liver Disease score was 10. Liver biopsy revealed diffuse nodular regenerative hyperplasia.

Results

The patient underwent liver transplantation with Model for End-stage Liver Disease exception points. Her oxygen requirements gradually improved during the postoperative period. The patient's symptoms and hypoxemia resolved at 15-month follow-up posttransplantation.

Conclusion

We suggest hepatopulmonary syndrome in this setting is an indication for liver transplantation despite the absence of cirrhosis.     

Sequential liver-kidney transplantation

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.     

Hemangiomas with localized nodular proliferation of the liver. A suggestion on the pathogenesis of focal nodular hyperplasia

Multiple cavernous hemangiomas circumscribed by focal regenerative nodules of hepatocytes were incidental findings at the autopsy of two elderly men. Neither patient was on steroids or had venous thrombosis. The lesions were not typical for other nodular proliferations of the liver, such as focal nodular hyperplasia, nodular regenerative hyperplasia, or liver cell adenoma, and they have not been previously reported. We also explore the roles of vascular malformation, oral contraceptives, and thrombosis in the pathogenesis of localized nodular proliferation of the liver.     

Two Brothers With Renal and Hepatic Polycystic Disease Treated With Combined Liver and Kidney Transplantation: A Case Report

We report two brothers with renal and hepatic polycystic disease who developed end-stage renal failure, requiring hemodialysis, and organomegaly syndrome related to the gigantic size of the liver and both kidneys. Although there was no liver failure, combined liver and kidney transplantation was performed owing to worsening of the clinical condition. In both cases, successful transplantation was accomplished with intra-abdominal engraftment of the liver and kidneys through the same abdominal incision.     

A case report: hepatic posttransplant lymphoproliferative disorder in a non-liver transplant patient

Posttransplant lymphoproliferative disorder (PTLD) is the most common malignancy in children after solid organ transplantation. We present a patient, who developed Epstein-Barr virus (EBV)-related PTLD in the liver after renal transplantation. A 10-year-old EBV-seronegative boy with cystinosis underwent a living related preemptive renal transplantation. He received antiviral prophylaxis with valacyclovir. At 5.5 months posttransplantation he displayed a primary EBV infection with an high fever, hepatosplenomegaly, monocytosis, and positive EBV DNA levels. Two months there after, a hypoechoic nodular 20-mm lesion in the left lobe of liver was detected on abdominal ultrasonography, performed because of anorexia and weight loss. EBV-DNA copy number was 7820 copies per milliliter. Liver biopsy showed a diffuse large B-cell lymphoma that was compatible with PTLD. We stopped all immunosupressive agents other than prednisolone. Chemotherapy consisting of two courses of cyclophosphamide, vincristine, prednisolone, and adriamycin was followed by rituximab. Within 2 months, the lesion resolved and within 18 months, he was free of disease.     

Hepatic resection for isolated tumor-like nodules in the liver

We have reported two cases of focal nodular hyperplasia of the liver in adults. One case is the first in which the regenerative process that occurred nine months after localized hepatic necrosis was implicated in the development of focal nodular hyperplasia. The other case concerned an idiopathic isolated liver nodule that occurred in a woman who never had taken oral contraceptives. These tumor-like lesions were removed by a right and a partial hepatectomy respectively. The two patients remained asymptomatic during the first 13 postoperative months with no additional therapy.     

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.     

临床肝肾移植三例体会

目的　探讨肝肾序贯移植和同期联合移植的手术难点及围手术期处理要点。方法　对2例肾移植术后发生药物性肝损害的病例实施肝移植 ,并对 1例巨大多囊肝、多囊肾的病例实施肝肾联合移植。结果　 2例肾移植术后实施肝移植的病例 ,其中 1例因术后肾功能衰竭导致多器官功能衰竭死亡 ;另 1例术后肝、肾功能良好 ,现已存活 1年。肝肾联合移植病例术中采用肝后腔静脉直接阻断法 ,使重达 10kg的巨大病肝得以顺利切除 ,并采用腔静脉成型术完成改良背驮式肝移植。术后免疫方案采用人源化单克隆抗体达利珠单抗免疫诱导下的以FK5 0 6、霉酚酸酯 (MMF)和激素的三联用药 ,肝、肾功能恢复良好 ,现为术后 6个月。结论　序贯性肝肾移植在术前应该准确评估移植肾功能 ,如果移植肾功能不良 ,应果断选择实施肝肾联合移植。肝后下腔静脉直接阻断法在实施巨大病肝切除时具有较大优势。肝肾联合移植术中及术后建议采用达利珠单抗免疫诱导下的免疫三联用药。     

Is Nodular Regenerative Hyperplasia of the Liver Associated with Azathioprine Therapy After Renal Transplantation?

A 33-year-old man presented with hepatosplenomegaly and ascites26 months after receiving a successful renal transplant. Immunosuppressionconsisted of low-dose prednisolone and azathioprine. Biopsyshowed characteristic features of nodular regenerative hyperplasiaof liver (NRHL), a condition which may be related to azathioprinetherapy but has rarely been reported in association with renaltransplantation.     

Resolution of hepatitis B virus-related membranoproliferative glomerulonephritis after orthotopic liver transplantation

The most well-described renal disease associated with hepatitis B virus (HBV) infection is membranous glomerulonephritis; membranoproliferative glomerulonephritis is described much less frequently. The course of HBV-associated renal disease after liver transplantation has not been described to date. We present a 15-year-old girl with HBV-associated membranoproliferative glomerulonephritis and end-stage liver disease, in whom, after cadaver liver transplantation, clinical and histological resolution of renal disease was observed. Resolution was associated with diminution of circulating HBV surface antigen levels.     

Living-donor liver transplantation with renoportal anastomosis for patients with large spontaneous splenorenal shunts

BACKGROUND: End-stage liver disease is often accompanied by large spontaneous splenorenal shunts and thrombosed portal vein. Renoportal anastomosis for spontaneous splenorenal shunts in living-donor liver transplantations is one of the solutions for the treatment of these patients. However, the long-term outcome, portal venous hemodynamics after liver transplantation, and the effects of altering the renal venous drainage remained unknown. METHODS: We performed three living-donor liver transplantations with renoportal anastomosis for the treatment of spontaneous splenorenal shunts between 1999 and 2004. We then evaluated the outcome of this procedure using short- and long-term follow-ups in which the postoperative graft function, renal function, radiological images and portal hemodynamics were examined. RESULTS: All three patients who underwent a living-donor liver transplantation with renoportal anastomosis are alive with normal graft function and a patent renoportal anastomosis. The portal hemodynamics were similar to those in conventional living-donor liver transplantation recipients, and had no harmful effect on allograft function. Left renal function returned to normal after the temporal impairment in two cases, and remained slightly impaired in one, although it was negligible clinically. CONCLUSIONS: Living-donor liver transplantation with renoportal anastomosis for the treatment of spontaneous splenorenal shunts in patients with end-stage liver disease is a life-saving and safe technique and should be discussed as a treatment option for patients with splenorenal shunts.     

Living related renal transplantation for end-stage renal disease after liver transplantation from a brain-dead donor

We report a case in which a living related renal transplantation was successfully performed for end-stage renal disease that had progressed after a liver transplantation from a brain-dead donor for liver cirrhosis associated with type C hepatitis. Because the transplanted liver function had been excellent with the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents with prednisolone were employed for the renal transplantation. Both grafts are functioning well without recurrence of hepatitis at 10 months after the renal transplantation. From our experience, renal transplantation should not be contraindicated even if the patient has undergone liver transplantation or has hepatitis C viral infection.     

Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor?

We report a patient who acquired hepatitis C virus (HCV) infection at cardiac transplantation, developing fibrosing cholestatic hepatitis (FCH) with early liver failure and a fatal outcome. FCH is a recently described clinicopathological entity characterized by a cholestatic pattern of serum liver enzyme abnormalities, a progressive course leading to liver failure, and a pathological picture defined by periportal fibrosis, neutrophilic infiltrates and signs of histological cholestasis. Although it was initially described secondary to hepatitis B virus infection, it has also been recently related to HCV infection. Some histopathological features consistent with azathioprine hepatotoxicity like cholestasis, perisinusoidal fibrosis, veno-subocclusive lesions and nodular regenerative hyperplasia were also observed in this case. Therefore, a direct cytopathic effect of HCV and the concurrent pathogenic role of azathioprine hepatotoxicity may be involved in the development of this complication of transplantation.     

Combined liver-kidney transplantation in polycystic disease: case reports

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.     

肝肾联合移植的临床体会（附10例分析）

目的总结肝肾联合移植的治疗体会。方法收集接受肝肾联合移植的10例患者的临床资料,对其手术时间、供肝和供肾热缺血时间、术中出血量、术后并发症,受者和移植物功能等情况进行总结分析。结果 10例患者的原发病分别为乙型病毒性肝炎（乙肝）后肝硬化5例,其中合并药物性肾衰竭1例、移植肾失功1例、肝肾综合征3例;原发性肝细胞癌合并肾衰竭2例;酒精性肝硬化合并尿毒症1例;先天性多囊肝和多囊肾（polycystic liver and kidney disease,PCLKD）1例;肝移植术后缺血性胆管狭窄并肾衰竭1例。肝移植采用改良背驮术式,肾移植采用常规移植方法,将移植肾置于左髂窝或右髂窝。手术均获成功,肝移植手术时间（444±175）min,肾移植手术时间（184±36）min;移植肝和移植肾热缺血时间为8min以内;术中出血量（3367±1726）ml。术前严重感染的5例,术后1周内死于多器官功能衰竭。存活的5例患者中,其中1例患者术后反复肺部感染,给予呼吸机辅助支持治疗、积极抗感染后治愈,其余4例患者无明显并发症。5例患者均存活,生存12~32个月,受者和移植物功能良好。结论肝肾联合移植是治疗终末期肝、肾功能同时受损的有效的不可替代的治疗手段。选择合适病例,把握适当的手术时机,术中控制手术时间、热缺血时间和出血量,术后积极处理并发症是获得良好疗效的关键。     

原位肝移植治疗终末期肝病9例初步报告

１９９３年９月至１９９６年７月分别为９例终末期肝病病人施行了原位肝移植术。其中４例为原发性肝脏恶性肿瘤，５例为良性终末期肝病。移植术式除１例背肽式肝移植和１例减体积肝移植外，其余７例均为原位全肝移植，并为１例多囊肝，多囊肾，合并肝，肾功能损害闰人施行了肝，肾联合移植术。