Prevalence of type 2 diabetes mellitus in Brazilian liver transplant candidates: negative association with HCV status.

Recently, an epidemiological association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM) has been reported in several studies, although many of them did not consider known risk factors in the pathogenesis of type 2 DM. The aim of this study was to assess the prevalence of type 2 DM among Brazilian HCV (+) and HCV (-) liver transplant candidates, analyzing known confounding factors for the development of type 2 DM. We conducted a cross-sectional study to evaluate the prevalence of type 2 DM among 106 liver transplant adult candidates, comparing 36 HCV (+) cirrhotic patients with 70 HCV (-) patients who developed cirrhosis from other causes. Type 2 DM was diagnosed after two consecutive fasting glucose values > or =126 mg/dL. The age, sex, and race distribution, severity of liver disease (Child-Pugh score), and family history of DM were similar in both groups, but the mean body mass index (BMI) was higher in the HCV (-) subjects (26.81 +/- 5.29 vs 24.0 +/- 4.71, P < .01) Most of the patients were Caucasians (70.75%). Type 2 DM was detected in 36.11% of HCV (+) group and in 25.71% of the HCV (-) (P = .27). A multivariate analysis revealed that family history of DM was the only significant independent predictor for DM (odds ratio = 2.55, 95% CI = 1.03 to 6.31, P = .04). In conclusion, our study did not show an association between HCV infection and Type 2 DM in Brazilian liver transplant candidates. It confirmed that the family history of DM was a determinant factor for the development of type 2 DM.

Prevalence of new-onset diabetes mellitus in Brazilian liver transplant recipients: association with HCV infection.

New-onset diabetes melittus (NODM) is a serious complication following transplantation. Recent studies suggest an association between hepatitis C virus (HCV) infection and DM both in nontransplant settings as well as after liver transplantation (LT). The aim of this study was to assess the prevalence of NODM among Brazilian LT recipients, analyzing possible risk factors including HCV infection. We conducted a cross-sectional study to evaluate the prevalence of NODM in 82 LT recipients with a posttransplant follow-up > or =1 year including 29 HCV-positive patients and 53 with other causes for liver disease. Patients were considered to meet the criteria for DM if they had two consecutive fasting glucose values > or =126 mg/dL or if they were taking insulin or oral hypoglycemic agents at the time of the study. The overall prevalence of NODM was 18.29% with a median interval of 20 months between LT and diagnosis of DM. The age, sex, and race distribution, immunosuppressive regimen, number of rejection episodes treated with pulse therapy, and family history of DM were similar in both groups. However, the frequency of BMI > or = 30 in the pre- and posttransplant periods was higher among patients who developed NODM (P = .02). Upon multivariate analysis of the entire cohort, HCV infection was the only significant predictor of NODM (OR = 4.31, CI = 1.17 to 15.84, P = .02). In conclusion, our study confirmed an association between HCV infection and NODM among Brazilian liver transplant recipients, suggesting that HCV infection may have a potential role in the pathogenesis of posttransplantation DM.

Donor quality of life after living donor liver transplantation.

Living donor liver transplantation (LDLT) for children and adults has gained widespread acceptance due to the severe organ shortage. LDLT provides potential recipients with timely transplantation, but this procedure engenders a potentially significant risk to the donor. This study analyzed medical, functional, and psychological donor outcomes after LDLT. Nineteen donors (mean age 33.9 +/- 12 years), who underwent hepatectomy for LDLT (13 right lobectomy for adult LDLT) from March 1998 to November 2002, were interviewed at a median of 13 months after donation (range, 2 to 58 months). According to the Clavien System classification, major complications occurred in three donors (16%), and minor in four (21%). The mean length of hospital stay was 5.7 +/- 1.6 days. Five patients (27%) needed rehospitalization. Complete recovery was achieved at a mean time of 8.5 +/- 3.5 weeks. All 19 donors were able to return to predonation activities. The donor's relationship to the recipient and to their families was improved after donation in all cases; 12 (63%) cited a positive psychological impact on their lives. About 90% would donate again and 84% would recommend donation to someone contemplating it. In conclusion, all donors are alive and well after donation and were able to return to their predonation occupation. Most of them felt that this experience changed their lives for the better and would donate again. Donor safety and quality of life should remain the priority in all donation processes.

Prevalence of malnutrition in liver transplant candidates.

OBJECTIVE: To determine the prevalence of malnutrition among liver transplant (LT) candidates. MATERIALS AND METHODS: A prospective study evaluated 219 adult LT candidates including 141 men and 78 women. Cholestatic disease was present in 21 (Child: A = 1, B = 11, and C = 9) and noncholestatic disease in 198 (Child: A = 12, B = 93, and C = 93. The mean age was respectively 45.6 and 46.5 years. Anthropometric and biochemical assessments were performed for statistical analysis using Student t test (P <.05). RESULTS: In the noncholestatic group, 41.5% were obese according to keep a body mass index (BMI); 61.6% were depleted according to adequacy of tricipital skin fold (%TSF); and 71.1% were above normal levels for generalized adipose reserve (%F). In terms of adequacy of mid-upper arm muscle circumference (%MMC), 58% were depleted and 50.5% were depleted for the current body weight/usual body weight (%CBW/UBW). Otherwise 52.2% of current body weight/ideal body weight (%CBW/IBW) values were above normal. Serum albumin was below normal in 64.9% of cases. In the cholestatic group 62% were normal for BMI; 66.7% were depleted for %TSF; 77.8% were above normal for %F. As to %MMC, 47.6% were depleted and 47.6% were depleted for %CBW/UBW. Otherwise 47.6% were above normal weight for %CBW/IBW. Serum albumin was below normal in 53.9% and %MMC values showed statistically significant differences (P =.02) when compared with Child B and C in the noncholestatic group, as well as %F (P =.01) and serum albumin (P =.0002) in the cholestatic and noncholestatic groups. Serum albumin values also showed statistically significant differences (P =.0004) when noncholestatic Child B and C patients were compared. CONCLUSION: Patients with cholestatic disease were more affected by calorie depletion compared to noncholestatic patients who were more affected by protein depletion.

Impact of successful liver transplantation on reproductive function and sexuality in women with advanced liver disease.

Abnormalities in the reproductive function and sexuality, which are common among women with advanced liver disease, may reverse after successful liver transplantation (LT). To analyze reproductive function and sexuality in women who underwent successful LT, we interviewed 28 recipients (mean age 44.17 +/- 13.6 years old) at a median posttransplant survival of 36.5 months (range, 6 to 110 months), with good graft function and obeying regular follow-up at our institution. In addition to medical records, all subjects answered a questionnaire on their menstrual pattern, sexual activity, contraceptive practice, pregnancy, and sexuality domain. Nineteen of 22 patients in the child bearing age (86.4%) recovered menstrual function at a median of 1 month after LT (range, 1 to 7 months). Twenty of 28 recipients (71.4%) were sexually active. The most frequent contraceptive practices were barrier methods and tubal ligation. There were four successful pregnancies (one twin) in three patients; five healthy babies were delivered. Overall, 70% of sexually active patients indicated satisfaction with their relationship, 75% had weekly intercourse, and 70% experienced orgasm with intercourse. Eighty percent expressed a desire to receive information concerning sexuality. In conclusion, LT has a positive impact on sexuality and reproductive function in female recipients. It would desirable that LT programs included information regarding these issues for this population.

[Apoptosis as a mechanism of tissue injury in hepatobiliary diseases]. / Apoptose como mecanismo de lesão nas doenças hepatobiliares.

BACKGROUND: Cell death by apoptosis is a fundamental biologic process involved in many physiologic and pathophysiologic processes in the liver. OBJECTIVE: To review the process of apoptosis, its cellular mechanisms, its regulation by external factors, and its role in pathophysiologic process and specific diseases of the liver. CONCLUSION: An understanding of the cellular mechanisms of apoptosis and their dysregulation during pathophysiologic disturbances will help in understanding human liver diseases. The modulation of apoptosis may lead to novel therapeutic strategies for the treatment of a wide range of liver diseases.

[Return to work of adults after liver transplantation]. / Retorno ao trabalho de pacientes adultos submetidos a transplante de fígado.

BACKGROUND: Orthotopic liver transplantation is an established therapy for patients with end-stage liver disease. In the last years more attention has been given for the improvement of the quality of life after liver transplantation, and the return to important life pursuits, such as employment, are important goals of this type of therapy. AIM: To assess the work's return rate in liver transplant recipients and the reasons for inability after liver transplant. PATIENTS AND METHODS: Forty-one adults (age > or = 18 years) who underwent liver transplantation at our institution, between September 1991 and June 1999, with a post-transplant survival > or = 9 months, good graft function and a regular clinical follow-up were enrolled for the study. A questionnaire that measured aspects of inactivity before and after liver transplantation had been applied. RESULTS: Thirty-one of 41 patients were unable to work due end-stage liver disease before liver transplantation. Return to work was observed in 28 of 41 patients (68%) in a mean time of 5.9 months after the surgical procedure. Eleven of 28 active patients after liver transplant (39%) contribute significantly to family income. The reasons for inactivity after liver transplantation were: early retirement (n = 5), unemployment (n = 4), and physical disability (n = 4). CONCLUSION: Successful liver transplantation not only improves the survival rate but allows patients to return to social function and workforce.

[Results of liver transplantation in patients with hepatocellular carcinoma]. / Resultados do transplante hepático em portadores de hepatocarcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies worldwide. Liver transplantation has emerged as a good option for early-stage hepatocellular carcinoma yielding survival rates as good as for recipients without this type of tumor. OBJECTIVE: To assess the outcome of cirrhotic patients with hepatocellular carcinoma undergoing liver transplantation at the Liver Transplantation Service of the "Hospital de Clinicas", Federal University of Paraná, Curitiba, PR, Brazil. METHODS: Retrospective study of cirrhotic patients with hepatocellular carcinoma undergoing orthotopic liver transplantation at the mentioned Institution between September 1991 and September 2000. The diagnosis of hepatocellular carcinoma was established during the pretransplant workup in five patients and the tumor was an incidental finding in the native liver in three. The indication for liver transplantation was restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with each nodule measuring less than 3 cm, and no evidence of vascular invasion or extrahepatic spread. Patient survival and evidence of tumoral recurrence posttransplant were evaluated. RESULTS: The most common cause for pretransplantation liver disease was hepatitis C virus (50%). On examination of the explanted liver, the majority of patients (6/8, 75%) had a single lesion; one patient had two nodules and one had a multifocal hepatocellular carcinoma found incidentally in the native liver. Tumor size ranged from 0.2 to 5.0 cm. All cases had neither vascular invasion nor linfonodal envolvement. All patients remained alive and free of tumor recurrence at the time of the study with a mean follow-up of 18.5 months (range, 5-29 months). CONCLUSION: Liver transplantation is a good therapeutic option for early stage hepatocellular carcinoma arising in cirrhotic patients. With proper selection, liver transplantation can offer excellent survival rates free of tumor recurrence.

[Normalization of menstrual cycles and pregnancy after liver transplantation]. / Normalização dos ciclos menstruais e gravidez após transplante de fígado.

The objective of the present study is to evaluate the effects of successful liver transplantation on menstrual cycles abnormalities and on reproductive function of women with chronic liver disease. Twelve women with age between 17 and 54 years who underwent liver transplantation were evaluated. The following variables were analyzed: age, etiology of chronic liver disease, pattern of menstrual function and period of amenorrhea before and after transplantation, and occurrence of pregnancy after transplantation. The mean age of patients was 36 +/- 12.6 years. Patients with primary biliary cirrhosis did not have menstrual abnormalities before transplantation. The other patients presented amenorrhea for 3 months to 11 years before the transplantation. Rapid recovery of menstrual function was observed in all patients after the transplantation (3.1 +/- 1.2 months). Two patients became pregnant one and three years after the transplantation. It is concluded from this study that most women who present amenorrhea secondary to chronic liver disease have normal menstrual cycles in approximately three months following liver transplantation and they may become pregnant.

[Acute cholestatic hepatitis induced by propylthiouracil. Case report]. / Hepatite aguda colestática pelo propiltiouracil. Relato de caso.

Propylthiouracil is widely used to treat patients with hyperthyroidism. However, propylthiouracil-induced hepatitis is an uncommon entity. The case of a 15-year-old boy treated with propylthiouracil for hyperthyroidism who developed a cholestatic acute hepatitis is reported. Viral, metabolic and autoimmune liver diseases were excluded and liver biopsy showed a pattern suggestive of drug-induced cholestatic hepatitis. After discontinuing the drug, there was a progressive resolution of symptoms and normalization of liver biochemical tests. Despite its rarity, patients receiving propylthiouracil are exposed to develop severe hepatotoxicity.

[Benign recurrent intrahepatic cholestasis: a seven-year follow-up report]. / Colestase intra-hepática recurrente benigna: seguimento de um caso por 7 anos.

Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder characterized by repeated episodes of intense pruritus and jaundice. Patients are completely asymptomatic for months to years between symptomatic periods. We report a case of a patient with a 7-year history of benign recurrent intrahepatic cholestasis. During the follow-up period the patient has suffered three attacks of cholestasis, confirmed by biochemical tests and histological exam. Liver enzymes were normal between the cholestasis episodes. Despite multiple attacks of cholestasis, no permanent liver damage has occurred. Although the diagnosis of benign recurrent intrahepatic cholestasis is rare, it should be included in the evaluation of a patient with cholestasis. The patients should be reassured of the benign course of this disorder.

[Amantadine-HCL in the treatment of chronic hepatitis C in non-responders to alpha-interferon. Effect on ALT serum levels and viral load]. / Cloridrato de amantadina no tratamento de portadores de hepatite crônica C não-respondedores ao alfa-interferon. Efeito sobre os níveis séricos de ALT e carga viral.

Due to the limited efficacy of alpha-interferon for chronic hepatitis C amantadine has been proposed as a possible alternative method of treatment. However, few studies about efficacy of amantadine in chronic hepatitis C are available with controversial results. Stimulated by recent data in the literature, we studied the effect of 100 mg of amantadine HCL (alone) PO bid, for a four month period on alanine aminotransferase serum levels and viral load in a cohort of 18 patients (14 males and 4 females) with chronic hepatitis C, non-responders to alpha-interferon. Inclusion criteria were: detectable serum HCV-RNA, alanine aminotransferase above the upper limit of normal, chronic inflammation on liver biopsy, no other associated chronic liver disease and written informed consent. Available biopsies showed initially four cases of cirrhosis, six of chronic persistent hepatitis and eight of chronic active hepatitis. The most prevalent HCV genotypes were 3a (n = 9, 52.94%) and 1b (n = 6, 32.29%). Viral load (Amplicor HCV Monitor, Roche, USA) and alanine aminotransferase levels were obtained at baseline and after four months of treatment. All patients enrolled into the study but one completed the treatment. One patient discontinued amantadine due to severe depression. No significant reduction was observed between baseline and final values of alanine aminotransferase (139.118 +/- 79.789 vs. 99.588 +/- 62.583 U/L, P = 0.059) and viral load (7.154 +/- 1.596 vs. 6.574 +/- 1.584 log copies/mL, P = 0.147). Amantadine alone was not effective neither eradicating viremia nor normalizing alanine aminotransferase levels in chronic hepatitis C non-responders to alpha-interferon patients. It is suggested that only a study with amantadine alone in-patients without previous treatments could determine its efficacy in comparison with alpha-interferon.

Isolated tuberculosis of the pancreas after orthotopic liver transplantation.

A patient presented with intermittent high fever, upper abdominal pain, and loss of appetite 9 months after an orthotopic liver transplantation. Computed tomography showed a large mass in the pancreas that was confirmed at laparotomy. Pathological examination of the pancreatic biopsy specimen showed several chronic granulomatous lesions with caseating necrosis. Two and one half months after beginning antituberculous treatment, there was an important reduction of the pancreatic mass.

[Multicenter study on the prevalence of hepatitis C virus infection in blood donors in the city of Curitiba, Brazil]. / Estudo multicêntrico da prevalência de infecção pelo vírus da hepatite C em doadores de sangue na cidade de Curitiba, Brasil.

In order to check the presence of anti-HCV in the blood of voluntary blood donors in four of the most active blood banks of Curitiba, PR, Brazil a third generation immunoassay (Murex--version III, ABBOTT AxSYM HCV version 3.0) was used. The study detected 347 positive cases, i.e. a median prevalence of 0.80% (range 0.64%-1.11%). Only 44 from the 347 anti-HCV positive blood donors had elevated values of serum aminotransferases (12.68%). Such low values of ALT suggest that the confirmatory RIBA should be applied to the remnant 303 anti-HCV positive cases (87.32%) which did not show elevation of ALT, with the expectation that 30% to 40% of them might be positive. The prevalence of anti-HCV in blood donors in Curitiba seems similar to published data in the Brazilian medical literature.