Review of the use of hepatitis B core antibody–positive kidney donors

This article reviews the risks of transplanting hepatitis B core antibody (anti-HBc)–positive (+) kidneys and strategies to minimize the risks to the recipient. In the United States, there is a shortage of kidneys available for transplantation. Presently, 4% of kidneys transplanted are anti-HBc (+). In published retrospective studies, the serologic conversion rate for recipients of anti-HBc (+) kidneys varied between 0% and 27%; and the development of elevated hepatic transaminases varied between 0% and 26%. Only one published article had a trend toward increased risk of graft loss. Other published studies had no significant difference in graft or patient survival. Factors that influence the risk of transmission include hepatitis B viral load, vaccination, and antiviral therapy. If the donor is anti-HBc (+) and hepatitis B DNA negative, the risk of transmission is negligible; unfortunately, this information may not be available at the time of transplant. Vaccinated recipients with a protective hepatitis B surface antibody of at least 10 mIU/mL had a 4% conversion rate compared with 10% in recipients with antibody levels not exceeding 10 mIU/mL. Both hepatitis B immunoglobulin and lamivudine have been used in recipients of anti-HBc (+) kidneys to decrease seroconversion with success. The data do support the use of anti-HBc (+) kidneys if precautions are taken. The recipients should be informed of the risk, should be vaccinated with an adequate response, and should have surveillance serologies performed.     

De novo hepatitis B after liver transplantation from hepatitis B core antibody—Positive donors in an area with high prevalence of anti-HBc positivity in the donor population

Transmission of hepatitis B virus (HBV) infection from donors who are negative for hepatitis B surface antigen (HBsAg−) but positive for antibody to hepatitis B core antigen (anti-HBc+) has been reported. However, previous studies were generally performed in geographic regions with a low prevalence of anti-HBc positivity in the liver donor population. The aims of this study are (1) to assess the risk for de novo hepatitis B in recipients of livers from anti-HBc+ donors in an area of high prevalence of anti-HBc positivity in the donor population, and (2) to analyze the risk factors for acquisition of HBV infection from anti-HBc+ donors. The transplantation experience of a single center between 1995 and 1998 was reviewed. Thirty-three of 268 liver donors (12%) were HBsAg− and anti-HBc+ during the study period. The proportion of anti-HBc+ donors increased with age; it was lowest (3.6%) in donors aged 1 to 20 years and highest (27.1%) in donors aged older than 60 years. Of the 211 HBsAg− recipients with 3 months or more of HBV serological follow-up, 30 received a liver from an anti-HBc+ donor and 181 received a liver from an anti-HBc− donor. Hepatitis B developed in 15 of 30 recipients (50%) of livers from anti-HBc+ donors but in only 3 of 181 recipients (1.7%) of livers from anti-HBc− donors (P < .0001). None of the 4 recipients who were antibody to HBsAg (anti-HBs)+ at the time of transplantation developed HBV infection after receiving a liver from an anti-HBc+ donor compared with 15 of 26 recipients (58%) who were anti-HBs− (P = .10). None of the 5 anti-HBc+ recipients developed hepatitis B compared with 15 of 25 anti-HBc− recipients (60%; P = 0.04). Child-Pugh score was significantly higher in recipients of livers from anti-HBc+ donors who developed HBV infection than in those who did not (9 ± 2 v 7 ± 1; P = .03). In our area, testing liver donors for anti-HBc is mandatory, particularly in older donors. With such information available, anti-HBc+ donors can be safely directed to appropriate recipients, mainly those with anti-HBs and/or anti-HBc at the time of transplantation. In the current era of donor shortage, this policy would allow adequate use of such donors. (Liver Transpl 2001;7:51-58.)     

Interferon-α in combination with ribavirin as initial treatment for hepatitis C virus–associated cryoglobulinemic membranoproliferative glomerulonephritis

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-α (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN. © 2001 by the National Kidney Foundation, Inc.     

Hepatitis C-related posttransplant plasma cell proliferative disorder with hepatitis C virus in neoplastic plasma cells: a new posttransplant disease entity?

Plasma cell proliferative disorder (PCPD) developed in two patients with actively replicating hepatitis C virus (HCV) in neoplastic plasma cells after orthotopic liver transplantation for HCV-related end-stage liver disease. PCPD was confined to the transplanted liver and was associated with monoclonal proteins in blood. Bone marrow biopsy did not show any evidence of PCPD. Epstein-Barr virus was not detected by in situ hybridization in either case. In situ hybridization for HCV RNA with sense and antisense probes in liver biopsy specimens showed signals in neoplastic plasma cells as well as in hepatocytes. We suggest that our patients had posttransplant PCPD resulting from HCV. It may represent a new posttransplant disease entity different from previously described posttransplant lymphoproliferative disorder. The findings raise intriguing questions about the role of HCV in PCPDs in patients with chronic HCV infection.     

Successful pregnancy in a liver transplant recipient treated with lamivudine for de novo hepatitis B in the graft

Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy. Liver transplant recipients with recurrent hepatitis C or hepatitis B nonetheless appear to be at risk of a worse graft function in the event of pregnancy, and antiviral drugs are generally contraindicated in pregnancy because of their teratogenic effects. A 33-year-old woman had undergone liver transplantation for Carolis disease 6 years previously. Two years later the patient experienced de novo HBV hepatitis. Lamivudine treatment (100 mg/day) was started and clearance of HBsAg was documented 1 year later. Four years after starting antiviral treatment the patient became pregnant, despite of the risk of teratogenic effects; lamivudine, cyclosporine and azathioprine were not discontinued for risk of break-through hepatitis and acute or chronic rejection. The course of gestation was uneventful and caesarean section was performed after 36 weeks. The newborn infant was a healthy male weighing 3,080 g and measuring 50 cm.     

Effect of donor–recipient age difference on long-term graft survival in living kidney transplantation

Purpose

We aimed to examine the influence of donor age on living-donor kidney transplantation (KTx), particularly with regard to long-term graft survival in young recipients with aged kidney grafts.

Methods

Between 1988 and 2012, 287 living-donor KTxs were performed in our center. The recipients were divided into 3 groups according to age in years: under 30 (young), 30–49 (middle-aged), and over 50 (old). The data regarding the influence of kidneys from donors aged over 50 years were retrospectively analyzed.

Results

Graft survival at 1, 5, 10, and 15 years was 94.7, 94.7, 90.2, and 75.2 %, respectively, in young recipients who received grafts from donors aged under 50 years, and 96.4, 91.9, 65.4, and 41.4 %, respectively, in young recipients who received grafts from donors aged over 50 years (P = 0.023). In contrast, there were no significant differences regarding graft survival and donor age in the middle-aged and old recipient groups. Multivariate analysis revealed that young recipient and rejection episode were significant predictors of graft loss in transplantation from older donors. Histological examination revealed significant age-related changes in the grafts before transplant and a significant higher rate of glomerular hypertrophy at the 1-month protocol biopsy in young recipients with aged kidney grafts.

Conclusions

Kidney grafts from older living donors affected long-term graft survival in young recipients. In addition to the damage from rejection, aged kidney grafts, which have less nephron mass, may have a limited capacity to appropriately respond to increases in physiological or metabolic demands of young recipients, leading to a greater reduction in renal function.     

Is it safe to use a liver graft from a Chagas disease-seropositive donor in a human immunodeficiency virus-positive recipient? A case report addressing a novel challenge in liver transplantation

This is the first report presenting a human immunodeficiency virus (HIV)-positive patient with fulminant hepatic failure receiving a liver graft from a Chagas disease-seropositive deceased donor. We describe the history of a 38-year-old HIV-positive female patient who developed fulminant hepatic failure of an autoimmune etiology with rapid deterioration of her clinical status and secondary multiorgan failure and, therefore, needed emergency liver transplantation (LT) as a lifesaving procedure. Because of the scarcity of organs and the high mortality rate for emergency status patients on the LT waiting list, we decided to accept a Chagas disease-seropositive deceased donor liver graft for this immunocompromised Chagas disease-seronegative patient. The recipient had a rapid postoperative recovery and was discharged on postoperative day 9 without prophylactic treatment for Chagas disease. Fifteen months after LT, she was still alive and had never experienced seroconversion on periodic screening tests for Chagas detection. Although there is an inherent risk of acute Chagas disease developing in seronegative recipients, our report suggests that these infected organs can be safely used as a lifesaving strategy for HIV patients with a high need for LT.     

Size or the number of portal tracts: which matters in a liver biopsy core in chronic hepatitis C?

Liver biopsy has an important role in staging of fibrosis (SoF) and grading of inflammation (GoI) in chronic hepatitis C (CHC) patients. The effect of size and number of portal tracts (NoP) on grading and staging of liver biopsy was evaluated. A total of 150 consecutive liver biopsy core (LBC) of patients with CHC were obtained. There were 98 (65.3%) males. Mean length of LBC was 1.45±0.48 cm. Mean number of portal tracts (NoP) was 11±4.6. Mean length of LBC was greater (1.60±0.45 cm) in stage 4 (n=41; 27.3%) and lesser (1.28+0.39) in stage 1 (n=23; 15%, p=0.04). The mean NoP were 8.5, 10.6 and 13.1 in GoI 1, 2 and 3 respectively (p<0.001). The mean NoP were 7.6, 11.1, 11.3 and 14.5 in SoF 1, 2, 3 and 4 respectively (p<0.0001). There was a good correlation between number of portal tracts and length of LBC (r2=0.56).     

The impact of low recipient weight [≤ 7kg] on long-term outcomes in 1078 pediatric living donor liver transplantations

Backgroundinfants who require liver transplantation represent a treatment challenge because chronic liver disease at this early age affects the child's growth and development during a critical phase. The aim is to compare demographics, operative data, and long-term outcomes according to recipient weight at the time of LDLT.MethodsThis retrospective study included primary LDLT analyzed in 2 groups: BW ≤ 7 kg (n = 322) and BW > 7 kg (n = 756). A historical comparison between periods was also investigated.ResultsBW ≤ 7 kg had significantly lower height/age and weight/age z-scores, with median PELD score of 19. Transfusion rates were higher in the BW ≤ 7 kg group (30.9 ml/kg versus 15.5 ml/kg, P < 0.001). Higher frequencies of PV complications were seen in the BW ≤ 7 kg cohort. HAT and retransplantation rates were similar. Those with BW ≤ 7 kg required longer ICU and hospital stays. Patient and graft survival were similar. Patient survival in BW≤ 7 kg was significantly better in the most recent period.ConclusionMalnutrition and advanced liver disease were more frequent in BW ≤ 7 kg. Despite increased rates of PVT and longer hospital stay, patient and graft long-term survival were similar between groups.     

Does donor–recipient age difference matter in outcome of kidney transplantation? Implications for kidney paired donation

Background: Kidney paired donation (KPD) is a rapidly growing modality for facilitating living donor kidney transplantation (LDKTx) for patients who are incompatible with their healthy, willing and living donor. The impact of donor–recipient age difference on long and short-term graft and patient survivals in LDKTx is still uncertain. Methods: A total of 1502 LDKTx recipients who received regular follow-up in our center from 1999 to 2012 were studied. Donor–recipient age difference was divided into subgroups (donor–recipient 0?10, 11–20, 0–20, 21–30, 31–40, and 21–40 years). Outcome measures included death censored graft, patient survival and acute rejection rate. Results: The 1-, 5-, 10-year patient survival of the donor–recipient age difference ≤20 years group showed no difference compared with the age difference >20 years group (94.5%, 83.2%, 71.9% and 95.2%, 86%, 77.8%, p?=?0.053). The 1-, 5-, 10-year graft survival of the donor–recipient age difference ≤20 years group showed no difference compared with the age difference >20 years group (94.6%, 81.6%, 72.1% and 94%, 80%, 72.2%, p?=?0.989). The rejection were also similar (17.5% vs. 16.5%, p?>?0.05). There was no statistically significant difference in graft survival and acute rejection rate in all subgroups. Conclusions: Older donors (usually within families) are not associated with worse outcome is reassuring. KPD should not be prohibited due to high donor–recipient age difference, when size of donor pool is small as in single center KPD program.     

A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus–infected patients awaiting liver transplantation

Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNA–positive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 × 10⁶ U/d; (2) group B, interferon alfa-2b, 3 × 10⁶ U three times weekly; or (3) group C, interferon alfa-2b, 1 × 10⁶ U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis. (Liver Transpl 2002;8:350-355.)     

Electro-physiological parameters of hepatic radiofrequency ablation—a comparison of an in vitro versus an in vivo porcine liver model

Background  Radiofrequency ablation (RFA) is an inherent part of curative treatment within a multimodal therapy concept of malignant liver tumors. The biggest problem is the high rate of local recurrences in tumors with a diameter of more than 3 cm because of the high variability and poor reproducibility of the zone of ablation. No imaging modality facilitates monitoring during neither intraoperativ nor percutaneous RFA. This experimental study describes and compares an in vitro and in vivo porcine model by its electro-physiological parameters with the aim of monitoring RFA procedures. Materials and methods  RFA was performed in a perfused in vitro porcine (one RFA per liver) and in vivo porcine model (24 animals) with three different RFA systems (Rita XL 5 cm, Rita XLi 7 cm, LeVeen 5 cm). In the in vivo model, percutaneous placement of the RFA device was guided by native and contrast-enhanced CT scan. The electro-physical parameters during RFA were online (in real time) recorded by a dedicated software. After the RFA, the livers were explanted, sliced, and measured according to the consensus technique. Results  The delivered energy was in vivo versus in vitro: Rita XL 238 ± 135 kJ versus 135 ± 53 kJ (p = 0.247); Rita XLi 711 ± 180 kJ versus 159 ± 54 (p = 0.016) and with LeVeen 212 ± 71 kJ (in vivo). The LeVeen system was inconsistent in the in vitro model. This correlates to an energy consumption per ml of necrosis in vivo versus in vitro Rita XL of 8 ± 3 kJ/ml versus 6.4 ± 3.9 kJ/ml (p = 0.537), Rita XLi of 10 ± 6 kJ/ml versus 1.8 ± 0.2 kJ/ml (p = 0.016), and LeVeen of 14.0 ± 12 kJ/ml (in vivo). The volume of ablation was in vivo versus in vitro Rita XL 30 ± 10 ml versus 26 ± 17 ml (p = 0.329), Rita XLi 90 ± 58 ml versus 88 ± 21 ml (p = 0.905), and LeVeen 22 ± 11 ml versus 50 ± 12 ml (p = 0.04). The impedance during RFA were in vivo versus in vitro Rita XL 39 ± 4 Ω versus 50 ± 14 Ω (p < 0.247), Rita XLi 33 ± 5 Ω versus 61 ± 16 Ω (p = 0.016) and LeVeen 31 ± 2 Ω (in vivo). Conclusion  The volume of ablation showed analogue data in vivo and in vitro. The delivered energy and energy consumption was in vivo up to five times (Rita XLi) higher than in vitro and the impedance in vivo was always lower than in vitro. These differences observed between in vivo and in vitro were more pronounced than previously described. Thus the use of an in vitro model for research of the RFA technique must be challenged. The large deployment of the Rita XLi was a problem for percutaneous positioning of the device without direct contact to liver surface or major vessels in 80-kg pigs and to a lesser extent in in vitro liver originating from 130- to 140-kg pigs. Modern RFA systems which generate large volume of tissue necrosis can therefore only be adequately tested in a porcine model with a liver weight of at least 1.5–2 kg. Alternatively, a bovine liver model (with a liver weight up to 10 kg) should be developed in the future. Best of Abstracts—Chirurgisches Forum 2009, Deutsche Gesellschaft für Chirurgie.     

Living donor liver transplantation in children: Should the adult donor be operated on by an adult or pediatric surgeon? Experience of a single pediatric center

Background/Purpose

Living donor liver transplantation has become a cornerstone for the treatment of children with end-stage hepatic dysfunction, especially within populations or countries with low rates of organ utilization from deceased donors. The objective is to report our experience with 185 living donors operated on by a team pediatric surgeons in a tertiary center for pediatric liver transplantation.

Methods

Retrospective analysis of medical records of donors of hepatic grafts for transplant undergoing surgery between June 1998 and March 2013.

Results

Over the last 14 years, 185 liver transplants were performed in pediatric recipients of grafts from living donors. Among the donors, 166 left lateral segments (89.7%), 18 left lobes without the caudate lobe (9.7%) and 1 right lobe (0.5%) were harvested. The donor age ranged from 16 to 53 years, and the weight ranged from 47 to 106 kg. In 10 donors, an additional graft of the donor inferior mesenteric vein was harvested to substitute for a hypoplastic recipient portal vein. The transfusion of blood products was required in 15 donors (8.1%). The mean hospital stay was 5 days. No deaths occurred, but complications were identified in 23 patients (12.4%): 9 patients experienced abdominal pain and severe gastrointestinal symptoms and 3 patients required reoperations. Eight donors presented with minor bile leaks that were treated conservatively, and 3 patients developed extra-peritoneal infections (1 wound collection, 1 phlebitis and 1 pneumonia). Eight grafts (4.3%) showed primary dysfunction resulting in recipient death (3 cases of fulminant hepatitis, 1 patient with metabolic disease, 1 patient with Alagille syndrome and 3 cases of biliary atresia in infants under 1 year old). There was no relation between donor complications and primary graft dysfunction (P = 0.6).

Conclusions

Living donor transplantation is safe for the donor and presents a low morbidity. The donor surgery may be performed by a team of trained pediatric surgeons.     

Auxiliary liver transplantation in acute liver failure in the rat – an illustrated description of a new surgical approach

INTRODUCTION: To investigate auxiliary liver transplantation successfully in rats suffering from acute liver failure, we developed a new surgical approach. METHODS: A 70% hepatectomized liver graft was implanted into the right upper quadrant of the abdomen. The donor portal vein was anastomosed with the recipient's right renal artery using the splint technique. The donor infrahepatic vena cava was attached onto the recipient vena cava end to side. The bile duct was implanted into the duodenum.     

Challenges in clinical–pathologic correlations: Acute tubular necrosis in a patient with collapsing focal and segmental glomerulosclerosis mimicking rapidly progressive glomerulonephritis

Herein, we report a case of acute kidney injury (AKI) due to diarrhea-induced acute tubular necrosis (ATN) in a patient with nephrotic syndrome secondary to biopsy-proven collapsing focal and segmental glomerulosclerosis (FSGS). The clinical picture mimicked rapidly progressive glomerulonephritis (RPGN) and motivated pulse therapy with methylprednisolone and cyclophosphamide. The case presentation is followed by a brief overview of the epidemiology of AKI in nephrotic syndrome as well as a discussion of its risk factors and potential mechanisms involved.     

Treatment of recurrent hepatitis C in liver transplant recipients: Is there any histologic benefit?

The benefit of antiviral treatment in recurrent hepatitis C after liver transplantation remains unclear. The aim of this study was to determine whether antiviral treatment improved histologic outcome in recurrent hepatitis C. All patients who were transplanted for hepatitis C from January, 1998 to December, 2000 were offered treatment with interferon alpha 2b (3 million units three times per week) and ribavirin (800 mg/d) for 1 year. All patients underwent liver biopsy before and after treatment. Virologic assay was performed at 3 months and at 1 year. Among the 33 patients, 13 managed 80% of total doses of both interferon and ribavirin. Dose reduction or discontinuation was necessary in others. In an intention to treat analysis, the overall virologic response at 3 months and 1 year was 27% and 12%, respectively. On an intention to treat basis, the overall histologic response showed little benefit. In the subgroup of patients who received full treatment, there was a trend towards benefit in regard to inflammation (per histologic activity index [HAI] score). However, the fibrosis score was comparable in both groups, and complete antiviral treatment did not improve the fibrosis score or prevent progression of fibrosis. In the posttransplant setting, it is often extremely difficult to give a full course of treatment with existing antiviral regimes. In an intention to treat analysis, the overall benefit of antiviral treatment in recurrent hepatitis C is disappointing, with little impact on the progression of fibrosis. (Liver Transpl 2003;9:354-359.)