Imatinib mesylate as a cause of acute liver failure

A 46-year-old patient diagnosed with chronic myeloid leukemia in whom cytogenetic and molecular remission had never been achieved was commenced on Imatinib Mesylate (Gleevec, Novartis Pharmaceuticals Corp., East Hanover, NJ). After 18 months of treatment, she developed abnormal liver function tests and subsequently acute liver failure, requiring transfer to the regional liver unit. The patient proceeded to liver transplantation but later died. The explanted liver had histological features of severe hepatic necrosis. This is the first case described of fatal hepatic necrosis in a patient who has have been on long-term imatinib therapy. This may have implications for long-term use of the drug and emphasizes the need for regular monitoring of liver function.     

Fulminant hepatitis from herpes simplex virus type 2 in an immunocompetent adult

Abstract: Herpes simplex virus (HSV) is regarded as a common viral pathogen that produces a wide variety of diseases. After a primary infection, which usually occurs during childhood and may or may not be clinically evident, the virus establishes a latent infection in the local sensory ganglia and can reactivate throughout the life of the individual. Fulminant hepatic failure (FHF) due to HSV infection is a clinical condition well known in pediatric, immunocompromised, and pregnant patients. It is rare in immunocompetent hosts. We report the case of a 51-year-old man with no significant past medical history who developed FHF with disseminated intravascular coagulopathy and septic shock secondary to HSV infection. The initial diagnosis was made through a frozen section of a needle liver biopsy and the presence of HSV was confirmed in the permanent section with immunohistochemistry. HSV was grown in cell culture from liver tissue obtained through an autopsy.     

A unique presentation of acute liver failure from herpes simplex virus hepatitis

We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival.     

Herpes simplex virus hepatitis after pediatric liver transplantation

T. Hori, Y. Ogura, S. Okamoto, A. Nakajima, K. Kami, J. Iwasaki, Y. Yonekawa, K. Ogawa, F. Oike, Y. Takada, H. Egawa, J.H. Nguyen, S. Uemoto. Herpes simplex virus hepatitis after pediatric liver transplantation
Transpl Infect Dis 2010: 12: 353–357. All rights reserved Abstract: Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought‐provoking case of HSV hepatitis in a high‐risk recipient after living‐related liver transplantation (LRLT). A 1‐month‐old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody‐mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real‐time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.     

Herpes simplex virus hepatitis 4 years after liver transplantation

If not promptly recognized and treated, herpes simplex virus (HSV) hepatitis is associated with a high mortality. A patient transplanted for primary sclerosing cholangitis required, 4 years later, a colectomy for a steroid-resistant flare of ulcerative colitis. He subsequently developed fever, with genital and oral ulcerations. He was hospitalized for diabetic decompensation with massive elevation of serum aminotransferases. Examination revealed vesicles on the hands. Liver biopsy showed Cowdry type B inclusions. Therapy with acyclovir was immediately initiated and the patient recovered. This case illustrates the diagnostic importance of mucocutaneous lesions in the assessment of complications after liver transplantation.     

Donor-derived fulminant herpes simplex virus hepatitis after liver transplantation: Two cases and review of literature

Background

Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor-derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients. The fatal outcome is mostly due to delayed diagnosis and treatment, which is explained by the lack of clinical specificity of HSV hepatitis.

Methods

We report two cases of fatal donor-derived HSV hepatitis in liver-transplanted recipients. We reviewed all published cases of donor-derived HSV infections after SOT with an evaluation of the presence of prophylaxis and outcome.

Results

In both liver recipients, the retrospective determination of HSV serostatus was negative, and both cases occurred in the absence of cytomegalovirus or HSV prophylaxis. A review of the literature showed a significant series of cases of severe hepatitis, mostly fatal, as well as the absence of specific preventive therapy guidelines in cases of HSV serology mismatch.

Conclusions

The occurrence of two fatal donor-derived hepatitis made the Swiss Transplant Infectious Diseases working group modify its national recommendations regarding pretransplant serostatus determination and HSV prophylaxis after liver transplantation. Further studies are needed to assess this approach.

     

Late‐onset visceral varicella‐zoster virus infection presented as acute liver failure after allogeneic hematopoietic stem cell transplantation

Although much less common than localized zoster, initial presentation of varicella‐zoster virus (VZV) as visceral infection can occur especially after allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of post‐transplant visceral VZV infection presenting as fatal acute liver failure. It developed 4 years after allogeneic HSCT when a long‐term prophylactic anti‐VZV agent administration was discontinued. VZV should be listed as a causative pathogen of acute liver failure even years after allogeneic HSCT. Indication for, and duration of anti‐VZV prophylaxis should be further investigated.     

Superficial herpes simplex virus wound infection following lung transplantation

Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution.     

High neutrophil-lymphocyte ratio indicates poor prognosis for acute-on-chronic liver failure after liver transplantation

AIM:To investigate the significance of pre-transplant neutrophil-lymphocyte ratio(NLR) in determining the prognosis of liver transplant(LT) recipients with acuteon-chronic liver failure(ACLF).METHODS:Data were collected from the liver transplantation data bank.The NLR values and other conventional inflammatory markers were evaluated for their ability to predict the prognosis of 153 patients with ACLF after LT.The NLR cut-off value was based on a receiver operating characteristic curve analysis.A Kaplan-Meier curve analysis and univariate and multivariate Cox regression models were used to define the independent risk factors for poor outcomes.RESULTS:The optimal NLR cut-off value was 4.6.Out of 153 patients,83(54.2%) had an NLR ≥ 4.6.The 1-,3-,and 5-year overall survival rates were 94.3%,92.5% and 92.5%,respectively,in the normal NLR group and 74.7%,71.8% and 69.8%,respectively,in patients with high NLRs(P 0.001).Furthermore,there was a significant difference in infectious complications after LT between the high and normal NLR groups.There were no significant differences for other complications.In the multivariate Cox regression model,a high NLR was defined as a significant predictor of poor outcomes for LT.CONCLUSION:A high NLR is a convenient and available predictor for prognosis of LT patients and can potentially optimize the current criteria for LT in ACLF.     

Kidney transplantation after liver transplantation

Kidney transplantation after liver transplanta-tion (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efifcacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta-tion because of calcineurin inhibitor (CNI)-induced neph-rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.     

Chronic herpes simplex virus type-2 infection and HIV viral load

By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan Africa was 7.5-8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection among adults aged >30 years ranged from 60% to 82%. However, little is known about the natural history of HIV/HSV-2 co-infection in this population. We evaluated HIV viral load and CD4+ cell counts among persons with and without chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2 infection (P=0.014). Chronic HSV-2 infection may have a negative effect on the clinical course of persons with HIV.     

Liver transplantation for acute-on-chronic liver failure

Purpose  

To evaluate the outcome of liver transplantation for acute-on-chronic liver failure.     

Inappropriate pemoline therapy leading to acute liver failure and liver transplantation

A 36-year-old female, presenting with jaundice, developed acute liver failure requiring orthotopic liver transplantation. On admission, none of the known causative factors for acute hepatitis, including use of drugs, were found to be present. Several days after hospitalization, the patient admitted taking therapy prescribed by a "non-traditional" physician, that she had been using for several years due to overweight and which had recently been modified with the introduction of pemoline. A considerable body of evidence exists in the medical literature showing that pemoline, which is a central nervous system stimulant, has variable hepatotoxic effects, ranging from a mild transient increase of serum transaminases to liver failure, including some lethal cases.     

Current management of hepatitis B virus infection before and after liver transplantation

The progress in treatment against hepatitis B virus (HBV) has substantially improved the outcome of all HBV‐infected patients. We systematically reviewed the existing data in the management of HBV transplant patients in order to assess the optimal regimen in the pretransplant setting, for post‐transplant prophylaxis and for therapy of HBV recurrent infection. All data suggest that an effective pretransplant anti‐HBV therapy prevents post‐transplant HBV recurrence. Pretransplant therapy has been based on lamivudine with addition of adefovir upon lamivudine resistance, but the use of newer, potent high‐genetic barrier agents is expected to improve long‐term efficacy. Moreover, it may lead to improvement of liver function, which sometimes removes the need for transplantation, although more objective criteria for removal from waiting lists are required. After liver transplantation, the combination of HBV immunoglobulin and one nucleos(t)ide analogue, mostly lamivudine, is currently the best approach, almost eliminating the probability of HBV recurrence. Treatment of post‐transplant HBV recurrence has been mainly studied with lamivudine, but it will be most effective with entecavir and tenofovir, which have a low risk of resistance. In conclusion, the newer anti‐HBV agents improve the treatment of HBV both pretransplant and post‐transplant. HBV immunoglobulin is still used in combination with an anti‐HBV agent for post‐transplant prophylaxis. Monoprophylaxis with one of the new anti‐HBV agents might be possible, particularly in patients preselected as having a low risk of HBV recurrence, but further data are needed and strategies to ensure compliance must be used.     

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.     

A case of acute liver failure due to hepatitis E virus,liver transplantation,and development of de novo autoimmune hepatitis

Acute hepatitis E virus (HEV) infection could lead to acute liver failure (ALF), which requires liver transplantation (LT). HEV infection could progress to chronic infection in an immunosuppressed host. De novo autoimmune hepatitis (AIH) is a rare occurrence of AIH during post‐LT immunosuppressive therapy in patients who underwent LT due to not AIH but some other etiology. Here, we report the first case of ALF due to HEV infection, the recurrence of HEV after LT that responded to ribavirin therapy, and then the development of de novo AIH showing a complete response to glucocorticoid therapy but multiple relapses after steroid withdrawal. This peculiar case suggests that HEV could have a pathogenic role in the development of the de novo AIH; additionally, this case report could help clinicians make therapeutic decisions in the post‐LT condition.     

肝移植患者医院内感染及其病原学特点

目的:研究肝移植患者医院内感染及其病原学特点。方法:对28例肝移植患者的临床资料及感染病原学资料进行回顾性分析。结果:28例肝移植患者医院内感染率为92.9%;感染例次为92例次,平均达3.29次。感染部位主要为腹腔、肺部和胆系,占84.8%。共分离各种病原菌132株,其中革兰氏阴性菌43株,占32.6%;革兰氏阳性菌58株,占43.9%;真菌31株,占23.5%。最常见的5种分离菌依次为凝固酶阴性葡萄球菌(28.0%)、铜绿假单胞菌(9.8%)、白色念珠菌(9.8%)、嗜麦芽寡养单胞菌(9.1%)、不动杆菌属(8.3%)。结论:肝移植患者医院内感染常见,影响患者预后,应注意预防。