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Problems during and after pregnancy of former biliary atresia patients treated successfully by the Kasai procedure.

BACKGROUND/PURPOSE: The aim of this study was to investigate the problems and the quality of life during and after pregnancy of the patients who had undergone Kasai operation and to find out a strategy for follow-up during the period of their pregnancy. METHODS: A questionnaire was sent to 134 institutions of the Japanese Biliary Atresia Society with the following questions: (1) Do you have any pregnancy cases in patients who had undergone Kasai operation? (2) Did she have any menstrual problem? (3) Did she have any problem during pregnancy and delivery? (4) Did she have any change in liver function tests after delivery? (5) Did she have any early and long-term problem after delivery? (6) Did the baby have any problem? (7) Was there any special care or comment about the pregnancy of the biliary atresia patients? The responses were analyzed. RESULTS: Fourteen institutions reported 16 cases of pregnancy, 23 cases of delivery, and 2 cases of abortion. The causes of abortion in the 2 cases were attributed to hemorrhagic shock after massive bleeding from esophageal varices and serious atopic dermatitis, respectively. Other problems during pregnancy were abruption of placenta, fetal distress leading to caesarian section, and development of liver dysfunction leading liver transplantation. Problems after delivery included deterioration of liver function in 6 patients (37.5%), attacks of ascending cholangitis in 4 patients (25.0%), and severe fatigue with liver dysfunction from nursing the baby leading to liver transplantation. Only 3 of 16 (18.8%) patients were free of any problems. No abnormality was seen in the babies. CONCLUSIONS: Even if the patients with biliary atresia lead a good postoperative course, unexpected complications can occur when they become pregnant. Close long-term follow-up is required for proper management of pregnancy in biliary atresia patients.

Adolescent↗

Independent risk factors and natural history of renal dysfunction in liver transplant recipients.

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m(2) from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m(2) for at least 6 months) were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m(2) /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m(2) were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m(2) from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m(2) occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients.

Adolescent↗

Epstein-Barr virus and persistent graft dysfunction after liver transplantation.

Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection.

Adult↗

Monitoring of T-cell repertoire was useful for predicting graft-versus-host disease prognosis in a patient with chronic myelogeneous leukemia after allogeneic bone marrow transplantation.

We analyzed 24 T-cell receptor (TCR)beta chain subfamilies (Vbeta) and the chimerism of a patient with chronic myelogeneous leukemia who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed liver dysfunction at day 19 leading to worsening of his condition. He died on day 91 of hepatic failure. Complete donor chimerism was observed after day 19. The average complexity score of TCR-Vbeta, which was low on day 19 (5.50), because much lower on day 82 (3.77). The average value of normal volunteers is 7.69. Neither immunosuppressive therapy nor antiviral therapy was effective to treat his hepatic dysfunction. A liver specimen at autopsy showed necrotic tissue with invasion of lymphocytes under the endothelial cells of the bile ducts. These findings suggest that the liver dysfunction was due to graft-versus-host disease (GVHD). Careful monitoring of chimerism and TCR-Vbeta complexity may help to predict the prognosis of GVHD after allogeneic BMT.

Adult↗

Intrahepatic mast cell population correlates with clinical outcome in biliary atresia.

PURPOSE: To determine if mast cells influence the clinical outcome in biliary atresia (BA), the authors examined the intrahepatic mast cell population in BA. METHODS: Mast cells were identified histochemically using Toludin Blue and immunohistochemically using antimast cell tryptase antibody in formalin-fixed paraffin-embedded sections from 21 cases of BA. Patients were divided into 3 groups; group I (n = 8) with good liver function, group II (n = 8) with moderate liver dysfunction, and group III (n = 5) with severe liver dysfunction. Liver biopsies from patients with choledochal cysts (CDC, n = 5), and normal liver (NL, n = 4) served as controls. The results were compared among the groups. RESULTS: Both histochemical and immunohistochemical methods showed similar data. Mast cells were seen mostly in the portal tracts. Mast cell numbers per medium power field (20 x magnification) were higher in BA than in the controls (15. 03 +/- 2.25 v 3.85 +/-.65, [mean +/- SEM], P <.05, BA v CDC; 15.03 +/- 2.25 v 1.73 +/-.06, [mean +/- SEM], P <.05, BA v NL, immunohistochemical data). Clinical correlation showed an association between higher mast cell number and liver dysfunction (32.62 +/-.80 v 8.52 +/-.87 [mean +/- SEM], group III v group I; P <. 05, immunohistochemical data). CONCLUSION: Increased mast cell population in BA adversely affects liver function and raises the possibility that type I allergic reaction may play role in the pathology of BA.

Biliary Atresia↗

Role of immunologic costimulatory factors in the pathogenesis of biliary atresia.

BACKGROUND: The authors studied the patterns of expression of immunologic costimulatory molecules (B7-1, B7-2, and CD40) in biliary atresia (BA) patients to confirm any correlation with clinical course/outcome. METHODS: Based on clinical status 2 years postoperatively, 24 BA patients were divided into group I (n = 8, normal liver function), group II (n = 10, anicteric with moderate liver dysfunction), and group III (n = 6, icteric with severe liver dysfunction). Liver biopsies obtained at portoenterostomy and from 6 age-matched controls, were analyzed immunohistochemically using antibodies against B7-1, B7-2, and CD40. RESULTS: There was no expression of B7-1, B7-2, or CD40 in any control liver specimen. In all BA specimens, B7-1, B7-2, and CD40 were expressed strongly in bile ductules in portal tracts. In groups with liver dysfunction, B7-1, B7-2, and CD40 were expressed strongly on the surfaces of Kupffer and dendritic cells and in hepatocyte cytoplasm. Positive staining cells were significantly fewer in patients with better clinical outcome. B7-1 was found in vascular and sinusoidal endothelial cells only in cases of postoperative portal hypertension. CONCLUSIONS: Costimulatory factors expressed on bile ductules, hepatocytes, and vascular endothelial cells appear to mediate autoimmune processes causing progressive liver fibrosis and portal hypertension in BA.

Antigens, CD↗

Levels of circulating antiinflammatory cytokine interleukin-1 receptor antagonist and proinflammatory cytokines at different stages of biliary atresia.

BACKGROUND/PURPOSE: Antiinflammatory cytokine (interleukin [IL]-1ra) and proinflammatory cytokines (tumor necrosis factor [TNF]- alpha and IL-6) appear to play important roles in the pathophysiology of liver disease. In this study, the authors attempt to identify the roles of IL-1ra, IL-6, and TNF-alpha at different stages in postoperative biliary atresia (POBA) patients. METHODS: Serum concentrations of IL-1ra, IL-6, and TNF-alpha were measured in 34 POBA patients and 25 healthy controls using specific enzyme-linked immunosorbent assays (ELISA). POBA patients were classified into 5 groups: group I (n = 21), less than 3 years old; Ia, stable; Ib, mild liver dysfunction; Ic, severe liver dysfunction. Group II (n = 13), (more than 3 years old); IIa, stable; IIb, variable liver dysfunction. RESULTS: For IL-1ra differences between controls and groups Ib, Ic, and IIa were statistically significant (P <.01), and for IL-6, differences between controls and groups Ia, Ib, Ic, and IIb were statistically significant (P <.01). Groups Ib and Ic (less than 3 years old subjects) had the highest levels in this series. Serum TNF-alpha was not detected in any groups. CONCLUSION: The relationship between serum levels of IL-6 and IL-1ra may be predictive of prognosis with respect to the progression of fibrosis in POBA patients.

Adolescent↗

[Preoperative evaluation of hepatic functional reserve for patients with primary liver carcinoma].

The retention rate of indocyanine green at 15 minutes (ICGR15) and routine hepatic function tests were performed preoperatively in 122 cases of patients with primary liver carcinomas in order to evaluate the hepatic functional reserve. These patients were divided into 3 groups according to the post-operative changes of hepatic function. 87, 24 and 11 cases showed good recovery (group good), mild liver dysfunction (group mild) and severe liver dysfunction (group severe) respectively, after operation. The differences of Pugh's points, ALT, ALP and gamma-GT between each two groups were not significant. But, the differences of ICGR15 were very significant. We also divided all cases into 3 groups according to the value of ICGR15. The incidence of liver dysfunction was 6.0% in group A (ICGR15 < 10.0%), 27.8% in group B (ICGBR15 = 10.0%-20.0%) and 76.5% in group C (ICGR15 > 20.0%), respectively. The difference of the incidences of liver dysfunction in these 3 groups was very significant. The higher the ICGR15, the more the incidence of liver dysfunction. These results demonstrated that ICGR15 is a good indicator to judge hepatic functional reserve for patients with primary liver carcinoma.

Adult↗

Incidence and risk factors of renal dysfunction after liver transplantation in Korea.

Renal dysfunction, one of the most common complications after liver transplantation, influences patient outcomes. Little is known, however, about it in Korea. The aims of this study were to determine the incidence and to identify the risk factors for renal dysfunction after liver transplantation. Sixty-two patients who survived over 6 months after transplantation were enrolled. Renal function was classified by creatinine clearance (Ccr, mL/min), which was estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed mild renal dysfunction (60 < or = Ccr < 90), and 27 patients (44%), moderate dysfunction (30 < or = Ccr < 60). The others were found to have normal function (Ccr > or = 90). None displayed severe dysfunction (Ccr < 30). Compared to a control group (Ccr > or = 60), the renal dysfunction group showed lower preoperative Ccr (91 +/- 28.6, 63 +/- 21.9, respectively, P < .01) and lower Ccr at 3 months after transplantation (72 +/- 17.1, 49 +/- 14.6, respectively, P < .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the frequency of postoperative acute renal failure did not affect the postoperative renal dysfunction. Twenty-six patients received mycophenolate mofetil while reducing the dose of calcineurin inhibitors because of compromised renal function. With mycophenolate mofetil treatment, the renal function seemed to improve, although the difference was not statistically significant (P = .057). These data demonstrate that renal dysfunction is common after liver transplantation and that preoperative renal function is the important factor predicting postoperative renal dysfunction.

Adolescent↗

Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases.

The medical records of 118 cases who met laboratory criteria of DIC were studied. The most frequent etiologies were: Generalized infection (39.8%), trauma (16.9%), malignancy (6.8%) and surgical cases (6.8%). The main clinical manifestations which appeared to be related solely to DIC were (in a decreasing order of frequency): Bleeding (64.4%), renal dysfunction (24.6%), liver dysfunction (18.6%), respiratory dysfunction (16.1%), shock (14.4%), thromboembolic phenonmena (6.8%) and central nervous system involvement (1.7%). In 26 patients none of these manifestations were observed. In patients with infection, liver and renal dysfunction were frequent and respiratory dysfunction rare, whereas in trauma cases, liver and renal dysfunctions were rare and respiratory dysfunction frequent. This variability indicates that the clinical manifestations are affected not only by the process of intravascular coagulation but also by the underlying clinical disorders. The most impaired coagulation tests were prothrombin time, partial thromboplastin time, platelet count and thrombin time. The degree of abnormality of these coagulation tests was found to be related to the extensiveness of organ involvement. The mortality (overall 54.7%) increased independently with age, with the number of clinical manifestations and with the degree of abnormality of the above-mentioned four most impaired coagulation tests. In addition, older patients were more likely to have an increased number of clinical manifestations and more impaired coagulation tests. Mortality was similar in the various etiologies except for trauma patients in whom it was lower (30%).

Adolescent↗

Liver biopsy in evaluation of complications following liver transplantation.

AIM: To analyze the role of liver biopsies in differential diagnosis after liver transplantation. METHODS: A total of 50 biopsies from 27 patients with liver dysfunction out of 52 liver transplantation cases were included. Biopsies were obtained 0-330 d after operation, in which, 44 were fine needle biopsies, another 6 were wedge biopsies during surgery. All tissues were stained with haemotoxylin-eosin. Histochemical or immunohistochemical stain was done. RESULTS: The rate of acute rejection in detected cases and total transplantation cases was 48.2% and 25.0%, chronic rejection rate in detected cases and total transplantation cases was 14.8% and 7.7%, preservation-reperfusion injury in detected cases and total transplantation cases was 25.9% and 13.5%, hepatic artery thrombosis rate in detected cases and total transplantation cases was 11.1% and 5.8%, intrahepatic biliary injury rate in detected cases and total transplantation cases was 7.4 % and 3.8%, CMV infection rate in detected cases and total transplantation cases was 3.7% and 1.9%, hepatitis B recurrence rate in detected cases and total transplantation cases was 3.7% and 1.9%, the ratio of suspicious drug-induced hepatic injury in detected cases and total transplantation cases was 11.1% and 5.8%. CONCLUSION: Acute rejection and preservation-reperfusion injury are the major factors in early liver dysfunction after liver transplantation. Hepatic artery thrombosis and prolonged cold preservation may result in intrahepatic biliary injury. Acute rejection and viral infection may involve in the pathogenesis of chronic rejection. Since there are no specific lesions in drug-induced hepatic injury, the diagnosis must closely combine clinical history and rule out other possible complications.

Acute Disease↗

Supplementation of antioxidants prevents oxidative stress during a deep saturation dive.

Conflicting views exist at the present regarding the influences of a deep saturation dive on liver function in divers. Therefore, we first reevaluated whether a deep saturation dive (400 msw) induces a hepatic disturbance. As the result, plasma activities of both transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) increased significantly, whereas cholinesterase (Ch-E) activity decreased markedly, being highly suggestive of liver dysfunction. Assuming that the liver dysfunction was attributable to oxidative stress, we next examined the effects of supplementation of antioxidants (600 mg of vitamin C, 150 mg of alpha-tocopherol, and 600 mg of tea catechins per day) on liver function in saturation divers. As was anticipated, the antioxidants taken appeared to prevent a hepatic disturbance, indicating that a deep saturation dive provokes liver dysfunction probably due to oxidative stress. Thus, we recommend that saturation divers should take supplements of antioxidants.

Adult↗

The risk of liver damage associated with minocycline: a comparative study.

Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000 EPM in those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.

Adolescent↗

Effect of troglitazone on the liver of a Gunn rat model of genetic enzyme polymorphism.

There is a possibility that serious liver dysfunction rarely observed in diabetic patients given troglitazone is attributable to idiosyncratic abnormalities in liver drug-metabolism. In addition, the results of blood biochemical examinations in serious cases of liver dysfunction showed a tendency for a high level of total bilirubin (T-Bil) over a long period compared with other indicators of liver dysfunction. Thus, we focused on genetic variation of UDP-glucuronosyltransferases (UGTs) that are involved in the conjugation of troglitazone and bilirubin. In this study, Gunn rats, which are hereditarily deficient in the UGT1 family of UGT isozymes, and Wistar rats, the parent strain of Gunn rats, were treated with troglitazone for 3 months at dose levels of 0, 100 or 400 mg/kg to investigate two possibilities: first, whether the genetic deficiency in UGT1s induces an alteration of the metabolic profile of troglitazone followed by liver dysfunction, and second, whether the dosing of troglitazone to Gunn rats which show hyperbilirubinemia result in liver dysfunction. As a result, the metabolic profile of troglitazone in Gunn rats was much the same as that of Wistar rats, suggesting that genetic deficiencies in UGT1s did not influence the metabolic profile of troglitazone. Moreover, no elevation of blood biochemical parameters, such as asparate aminotransferase (AST) and alanine aminotransferase (ALT), or histopathological liver injuries, such as hepatocellular degeneration and necrosis, were observed in either strain of rats, and hyperbilirubinemia in Gunn rats was not aggravated by the dosing of troglitazone. These results strongly suggest that troglitazone was not metabolized by UGT1s but by other UGT isozyme (s) in rats, and that glucuronidation of troglitazone did not compete with glucuronidation of bilirubin in vivo. Thus, it is suggested that high levels of total bilirubin in patients with liver dysfunction induced by troglitazone are attributable to hypofunction due to hepatocellular injury, not to metabolic competition of bilirubin with troglitazone. Moreover, it is also suggested that the deficiency in the UGT1 family of UGT isozymes itself may not be the cause of liver dysfunction associated with troglitazone treatment.

Animals↗

Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection.

Liver-enhancing modalities, such as portal vein embolization, are increasingly employed prior to major liver resection to prevent postoperative liver dysfunction. Selection criteria for such techniques are not well described. This study uses CT-based volumetric analysis as a tool to identify patients at highest risk for postoperative hepatic dysfunction. Between July 1999 and December 2000, a total of 126 consecutive patients who were undergoing liver resection for colorectal metastasis and had CT scans at our institution were included in the analysis. Volume of resection was determined by semiautomated contouring of the liver on preoperative volumetrically (helical) acquired CT scans. Hepatic dysfunction was defined as prothrombin time greater than 18 seconds or serum bilirubin level greater than 3 mg/dl. Marginal regression was used to compare the predictive ability of volumetric analysis and the extent of resection. The percentage of liver remaining was closely correlated with increasing prothrombin time and bilirubin level (P < 0.001). After trisegmentectomy, 90% of patients with </=25% of liver remaining developed hepatic dysfunction, compared with none of the patients with more than 25% of liver remaining after trisegmentectomy (P < 0.0001). The percentage of liver remaining was more specific in predicting hepatic dysfunction than was the anatomic extent of resection (P = 0.003). Male sex nearly doubled the risk of hepatic dysfunction (odds ratio = 1.89, P = 0.027), and having </=25% of liver remaining more than tripled the risk (odds ratio = 3.09, P < 0.0001). Hepatic dysfunction and </=25% of liver remaining were associated with increased complications and length of hospital stay (P < 0.0001 and P = 0.0003, respectively). Preoperative assessment of future liver volume remaining distinguishes which patients undergoing liver resection will most likely benefit from preoperative liver enhancement techniques such as portal vein embolization.

Adult↗

Graft calcifications and dysfunction following liver transplantation.

BACKGROUND: The molecular events, following ischemia and reperfusion (I/R) of the liver during transplantation are largely unknown. There is evidence that apoptotic and necrotic events may take place, and occasionally result in primary graft dysfunction. We herein report two cases, where significant I/R injury correlated with the development of liver calcification and primary liver dysfunction. CASE PRESENTATION: Both patients with clinical and biochemical evidence of primary graft dysfunction demonstrated calcification at light and electron microscopy levels. In addition, one patient had macroscopic evidence of calcification on cross-sectional imaging. Both patients died secondary to the sequelae of the graft dysfunction. CONCLUSIONS: Severe I/R-induced injury to the liver, clinically leads to graft dysfunction. This is due to advanced apoptotic and/or necrotic events at the hepatocyte level that may, on the most severe form, lead to calcification. The study of microcalcification at the early posttransplant period could provide insight in the events taking place following significant ischemia/reperfusion-induced injury to the graft.

Adult↗

Occurrence of cytomegalovirus hepatitis in liver transplant patients.

The differential diagnosis of liver dysfunction after orthotopic liver transplantation can be difficult. Cytomegalovirus (CMV) hepatitis is one possibility. This report reviews our experience with 17 cases of pathologically proven CMV hepatitis following liver transplantation and demonstrates the need for percutaneous liver biopsies to establish the diagnosis. There were seven pediatric patients (ages 2-11 years, five males, two females) and ten adult patients (ages 17-53 years, eight males, two females). The most common symptoms were prolonged fever (15 patients, with a mean duration of 22 +/- 5.5 days), elevation in total bilirubin (14 patients), and elevation in liver enzymes (15 patients); all symptoms were also found in rejection. Leukopenia and thrombocytopenia, reported to frequently occur with CMV infection, were found in only three and five patients, respectively. Twelve patients with the above symptoms underwent percutaneous biopsy on one or more occasions to differentiate CMV hepatitis from rejection. The diagnosis was made at retransplantation in five patients. CMV hepatitis followed treatment for acute rejection in 14 patients and occurred without additional immunosuppression in three patients. All patients were maintained on cyclosporine and prednisone. Acute rejection episodes were treated with a 5-day tapering dose of steroids (17 courses in 12 patients), OKT3 monoclonal antibody [Ortho (4 patients)] antithymocyte globulin [Upjohn (2 patients)], and azathioprine (1 patient). CMV was isolated from urine (nine patients), blood (nine patients), throat (seven patients), lungs (two patients), and other organs (two patients). CMV was cultured from the liver biopsy specimens in five of the seven attempts in pediatric patients. When the diagnosis was confirmed in the absence of rejection, immunosuppression was routinely lowered. When rejection occurred concomitantly with CMV hepatitis, therapy had to be individualized. Retrospectively, three patients treated for rejection were noted at retransplantation to have only CMV hepatitis, and all three patients died. A high index of suspicion and the judicious use of liver biopsies is essential in order to differentiate CMV hepatitis from other causes of posttransplant liver dysfunction.

Adolescent↗

Adverse effects associated with the use of South African traditional folk remedies.

UNLABELLED: Although the toxicity of traditional folk remedies is well known in Africa, it is a subject which is surrounded by secrecy and has not been comprehensively studied. OBJECTIVES: The aims of this study are to describe the clinical features of patients admitted to hospital with a confirmed history of using folk remedies, and to gather data on their toxicity in a systematic fashion. DESIGN: Prospective case series. SETTING: Paediatric and adult wards of academic hospitals in Johannesburg, South Africa. SUBJECTS: The study population included 103 patients ranging from one day to 75 years of age, all of whom had recent folk remedy use. MAIN OUTCOME MEASURES: All available clinical data were analysed. Primary outcomes were the presence of renal and liver dysfunction, death or discharge from hospital. RESULTS: The most common clinical features on presentation were dehydration (51%), vomiting (46%), jaundice (40%), diarrhoea (39%), altered mental status (37%) and oligoanuria (30%). Renal dysfunction was present in 76% of patients and liver dysfunction in 48%. The overall mortality was 34%. The odds ratio of death was 5.1 (95% CI 1.41 to 18.5) in patients with renal dysfunction (p = 0.0077) and 5.35 (95% CI 1.99 to 14.4) in patients with liver dysfunction (p = 0.0006). CONCLUSION: Renal and liver dysfunction are frequently associated with use of folk remedies, and mortality in these patients is high. In view of the large numbers of African individuals living in the United States and Europe, it is important for physicians elsewhere to be aware of the potential toxicity of African folk remedies, and to inquire about their use.

Adolescent↗