Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center.

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Recurrent hepatitis C treatment with direct acting antivirals - a real life study at a Brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.

Clinical Profile of Patients With Diabetes Mellitus and Liver Transplantation: Results After a Multidisciplinary Team Intervention.

BACKGROUND: Over the years, survival after liver transplantation has increased and metabolic complications are becoming more common, contributing to patients' morbidity and mortality. The objectives of this study were to describe a population of patients with hepatic transplantation and diabetes mellitus (DM), evaluate the frequency of metabolic complications, and assess the impact of a multidisciplinary team on DM management. MATERIALS AND METHODS: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital, all evaluated by a multidisciplinary team. RESULTS: Of all patients, 76.1% were men, with a median age 60 years old (interquartile range: 56 to 65 years) and liver transplantation time of 5 years (interquartile range: 0.6-9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). Regarding nutritional status, 37.9% of patients were classified as overweight according to body mass index, and 41.2% were considered overweight according to the triceps skin fold. The median glycosylated hemoglobin and weight before and after intervention of the multidisciplinary team in all 46 patients were, respectively, 7.6% (5.7% to 8.8%) versus 6.5% (5.7% to 7.7%); P = .022 and 70.5 kg (64.7 to 82.0 kg) versus 71.6 kg (65.0 to 85.0 kg); P = .18. CONCLUSIONS: Hypertension and dyslipidemia were common in transplanted patients with DM. Intervention of the multidisciplinary team resulted in a significant improvement in glycosylated hemoglobin without significant weight gain.

Frequency of Thyroid Dysfunction in Patients With Diabetes Mellitus Before and After Liver Transplantation.

BACKGROUND: There is mutual influence between the liver and thyroid hormone metabolism. Patients with diabetes mellitus (DM) also have an increased prevalence of thyroid disorders (TDs). The objectives of this study were to evaluate the frequency of TD before and after liver transplantation (LT) in a population of patients with DM as a whole and when categorized by sex. MATERIALS AND METHODS: This was a retrospective study involving interview and medical record analysis of 46 consecutive patients followed at the diabetes mellitus and liver transplantation unit of a tertiary university hospital. RESULTS: Of all patients, 76.1% were men with a median age of 60 years old (interquartile range: 56 to 65 years) and time since LT of 5 years (range, 0.6 to 9 years). Hypertension, hypercholesterolemia, hypertriglyceridemia, alcoholism, and smoking were present in 47.8%, 34.8%, 23.9%, 34.8%, and 30.4% of the patients, respectively. The most frequent immunosuppressant in use was tacrolimus (71.1%). TD was present in 4.3% and 13% before and after LT, respectively (P = .058). In women and men, these frequencies were 9.1% and 18.2% (P = .563), and 2.9% and 11.8% (P = .045), respectively. CONCLUSIONS: Frequency of TD was high both before and after LT. After transplantation, prevalence of TD increased in men and differences between males and females almost disappeared. Further studies are needed to assess if screening for TD before and after LT in patients with DM might be beneficial, especially in men.

Acute Liver Failure-25 Years at a Single Center: Role of Liver Transplantation in the Survival of Adult Patients.

BACKGROUND: Acute liver failure (ALF) leads to high morbidity and mortality and is characterized by an accelerated deterioration of hepatic function in patients without prior liver disease. The survival rate is <15% without liver transplantation (LT). The aim of this study was to describe the population of patients with ALF in the Unit of Liver Transplantation of the University of Campinas, Brazil, from 1991 to 2017, comparing those submitted and not submitted to LT. METHODS: The patients were divided into 2 groups: 1, listed but not transplanted; and 2, transplanted. RESULTS: There were 73 patients with ALF listed for LT, with a mean age of 33.6 years, 49 (67.1%) female and 24 (32.9%) male. Group 1, with 32 patients, had a mean age of 29.3 years; 26 (81.25%) died on the waiting list; 6 (8.45%), with a mean age of 12.33 years, were removed from the list because of recovery of liver function. Considering only adult patients, the mortality without LT was 96.29%. Group 2 had 41 patients, with a mean age of 37.1 years, and a 30-day survival of 41.02%. Thus, LT led to a significant improvement in the survival of adult patients with ALF. The time of surgery, packed red blood cells, and intraoperative plasma, were associated with LT survival after logistic regression study, whereas age, body mass index, bilirubin, international normalized ratio, creatinine, sodium, and Model for End-Stage Liver Disease score were not. CONCLUSIONS: ALF affects an active age range, and LT decreases mortality; there was no good preoperative prognostic indicator to assess which patients would benefit from transplantation.

Acute Liver Failure Induced by Carthamus tinctorius Oil: Case Reports and Literature Review.

BACKGROUND: Acute liver failure (ALF) is a clinical syndrome that results from the abrupt loss of liver function in a patient without previous liver disease. The most frequent causes are viral hepatitis, drug induced, and autoimmune disease, but in 20% of cases no cause is identified. Carthamus tinctorius (safflower) oil is used as a dietary supplement for weight loss and antioxidant. There are 4 cases described in the literature of ALF induced by the use of this substance. The objective of this study was to report 3 cases of ALF treated at the Clinical Hospital of the State University of Campinas that suggest the use of C tinctorius oil as a probable etiologic factor. CASE REPORTS: The 3 patients had a diagnosis of ALF according to the King's College criteria. All had a history of ingestion of this oil for weight loss. During etiologic evaluation, viral hepatitis, autoimmune diseases, or any other drug cause were excluded, thus pointing to C tinctorius oil as the triggering factor. All 3 patients underwent liver transplantation: 2 had good postoperative evolution, and 1 died 12 days after the procedure. CONCLUSIONS: Two cases are described in which the hepatic insufficiency induced by C tinctorius oil was successfully treated through liver transplantation. This highlights the risk of misuse of this substance for weight loss.

Association Safety of Liver Preservation Solutions at the State University of Campinas From 2010 to 2014.

The probable reason for mixing solutions during the harvesting procedure is due to the presence of multiple transplant teams that have their own solution usage tradition. Despite numerous studies comparing the efficacy of different preservation solutions, there is no study addressing the associating solution and if there is any impact on liver graft and patient survival. The aim was to evaluate the effect of the association of preservation solutions during the harvesting procedure on liver transplantation outcomes, especially in relation to the degree of preservation injury in the postreperfusion period and patient survival. We analyzed 206 transplants that were distributed as follows: when there was association (89/206 = 43.2%) and when there was no association (117/206 = 56.8%). There was a statistically significant difference in relation to the degree of preservation injury correlated to cold ischemia time (P = .009, odds ratio 1.992; 95% confidence interval 1.185-3.347). Severe harvesting (grades III and IV) was 71.8% when the solution was not associated (P = .008). There was no difference regarding patient survival either. We found that the association of liver preservation solutions has no impact on patient survival, so it can be done safely. The best survival rate was associated with minimal harvesting.

Immunomodulation, Acute Renal Failure, and Complications of Basiliximab Use After Liver Transplantation: Analysis of 114 Patients and Literature Review.

Basiliximab is considered to be effective in preventing cellular rejection (CR) in solid organ transplantation and is commonly used for renal transplants. The aim of this study was describe the population of patients undergoing orthotopic liver transplantation (LT) receiving basiliximab in the period 2012-2016 in the liver transplant service at the State University of Campinas, São Paulo, Brazil. We analyzed 114 patients who underwent LT and received basiliximab; 83 (72.8%) were male and 31 (27.2%) female, with an overall mean age of 54.3 years. Immunosuppression was performed with corticosteroids during anesthetic induction, and postoperatively with tacrolimus in 85.5%, sodium mycophenolate in 81.7%, cyclosporine in 12.7%, and everolimus in 15.5% of patients. CR was observed in 25.43% of patients, confirmed by biopsy in 15 patients: 50% acute CR, 21.42% late acute CR, and 28.57% chronic CR. Thus, the data are consistent with the literature regarding the benefit of using basiliximab as induction therapy while reducing the incidence of CR after LT, but on univariate analysis to evaluate factors associated with the occurrence of CR, the analyzed variables did not present statistical significance. There was acute renal failure (ARF) in 46.84% of patients and hemodialysis was performed in 20% of cases. In a previous series in our service, there was an ARF rate of 50%, so the incidence reduction of ARF after basiliximab use was 3.16%. Moreover, there was 6.95% hepatic artery thrombosis, 2.6% portal vein thrombosis, 2.6% biliary fistulas, 17.4% pneumonia, and 3.4% sepsis, which did not differ from the literature or from our earlier study without the use of basiliximab, suggesting the safety of this medication. In conclusion, in this series, basiliximab influenced the decrease of the CR incidence with no proven benefit on improvement in the ARF.

Immunoexpression of Heat Shock Protein 70, Glypican 3, Glutamine Synthetase, and Beta-Catenin in Hepatocellular Carcinoma After Liver Transplantation: Association Between Positive Glypican 3 and Beta-Catenin With the Presence of Larger Nodules.

BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. Its recurrence ranges from 6% to 26%. In the literature, many factors are associated with higher risk of recurrence, without a clear definition of the best method that could predict this highly lethal event. OBJECTIVE: The aim of this study was to evaluate the immunoexpression of immunohistochemical markers: HSP70, glypican 3, glutamine synthetase, and beta-catenin, as well as studying their association with tumor characteristics and prognosis of patients undergoing liver transplantation for HCC. METHODS: We studied 90 patients who underwent liver transplantation from 1998 to 2012. Afterwards we evaluated factors related to survival, tumor recurrence, and the correlation of expression of the immunohistochemical markers. RESULTS: Immunohistochemical marker glutamine synthetase showed a positive trend toward better survival. HSP70-positive patients had a higher prevalence of histologic grade III. Patients with positive glypican 3 showed larger lesions and a higher number with AFP >200 ng/mL. Patients with positive beta-catenin showed larger nodules and more with histologic grade III. The association between beta-catenin and glypican 3 showed positive association with larger nodules. CONCLUSIONS: Most of the markers studied had a correlation with at least one of the variables studied, confirming our hypothesis that these markers can indeed assist in assessing the prognosis of patients undergoing liver transplantation for HCC.

Factors Related to Hepatocellular Carcinoma Recurrence After Liver Transplantation-A Brazilian Multicenter Study.

BACKGROUND: Liver transplantation (LT) is a curative treatment option for hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R) is diagnosed in 9%-16%. The objective of this study was to evaluate which factors are associated with R-HCC after liver transplantation. METHODS: This retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093 LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in 40 patients (14.4%). RESULTS: Most of them were male with cirrhosis secondary to viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold ischemia time >8 hours. From the explant analysis, most of the patients were outside Milan criteria and 37.5% had microvascular invasion. The donors were mostly male, and the median intensive care unit time was >3 days. The Kaplan-Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P = .02), and older donors and more blood transfusions were risk factors for HCC-R death. CONCLUSION: AFP >200 ng/mL was associated with lower survival, and older donors and more blood transfusions were risk factors for death after HCC-R. A trend to lower survival was observed in patients who did not have chemoembolization and had cold ischemia times >8 hours.

Hepatic Artery Thrombosis After Liver Transplantation: Five-Year Experience at the State University of Campinas.

BACKGROUND: Hepatic artery thrombosis (HAT) is reported in 4%-15% of orthotopic liver transplants. Risk factors include technical error in the anastomosis, vascular anatomic variation, and high microvascular resistance. The aim of this study was to verify the incidence of HAT, early or late, and possible risk factors. METHODS: This was a retrospective study from January 2007 to December 2012 at the State University of Campinas. Variables analyzed were age, sex, cold and warm ischemia times, underlying disease, presence of hepatocellular carcinoma, Model for End-Stage Liver Disease (MELD) score, arterial anatomic variation in the graft, cytomegalovirus (CMV) infection, rejection, biliary complications, retransplantation rate, and survival. RESULTS: The incidence of HAT was 21/263, or 7.9%. Pure average MELD score was 22 ± 7.4. There was vascular anatomic variation in the graft in 14.2% of cases, in the majority (66.6%) a right hepatic artery from the superior mesenteric artery, and 4.76% of patients had CMV infection and acute cellular rejection (1 case each). There were biliary complications in 38% of patients, 13.3% of cases in patients with early HAT, and 100% of patients with late HAT (P = .002). Body mass index in late HAT was higher (P = .01). CONCLUSIONS: Late HAT was related to a significant increase in biliary complications (stenosis), and the survival rate was similar at 5 years.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation.

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.

Evaluation of Recurrence Predictors and Survival Probability After Liver Transplantation for Hepatocellular Carcinoma: Analysis From a Single Center.

BACKGROUND: Liver transplantation is the criterion standard treatment for hepatocellular carcinoma, but tumor recurrence remains a problem leading to a worse prognosis. We aimed to evaluate factors associated with recurrence of hepatocellular carcinoma and survival after this procedure. METHODS: We retrospectively reviewed data from 101 patients submitted to liver transplantation because of hepatocellular carcinoma from January 2005 to January 2012 at our single center. Univariate and multivariate analyses were performed to identify preoperative factors and histologic findings associated with lower survival rates and recurrence. The significance level was 5%. RESULTS: There was recurrence in 10 cases (9.9%), with an average time of 25.28 ± 26.92 months. Microvascular invasion (P = .005; hazard ratio [HR], 4.94; 95% confidence interval [CI], 1.42-17.12) was an independent factor for recurrence. Microvascular invasion (P = .035; HR, 1.87; 95% CI, 1.04-3.25) and tumors outside the criteria of the University of San Francisco (P = .046; HR, 1.81; 95% CI, 1.01-3.25) were independent factors for the risk of death. Poorly differentiated tumors had a higher level of alphafetoprotein (P = .03), and values <100 ng/mL were associated with well differentiated tumors. CONCLUSIONS: Microvascular invasion was associated with recurrence and lower survival. Tumors outside the criteria of the University of California, San Francisco had lower survival. Alpha-fetoprotein levels >100 ng/mL were associated with poorly differentiated tumors.

Variables associated with the risk of early death after liver transplantation at a liver transplant unit in a university hospital.

BACKGROUND: Graft dysfunction after liver transplantation is a serious complication that can lead to graft loss and patient death. This was a study to identify risk factors for early death (up to 30 days after transplantation). METHODS: It was an observational and retrospective analysis at the Liver Transplantation Unit, Hospital de Clinicas, State University of Campinas, Brazil. From July 1994 to December 2012, 302 patients were included (>18 years old, piggyback technique). Of these cases, 26% died within 30 days. For analysis, Student t tests and chi-square were used to analyze receptor-related (age, body mass index, serum sodium, graft dysfunction, Model for End-Stage Liver Disease score, renal function, and early graft dysfunction [EGD type 1, 2, or 3]), surgery (hot and cold ischemia, surgical time, and units of packed erythrocytes [pRBC]), and donor (age, hypotension, and brain death cause) factors. Risk factors were identified by means of logistic regression model adjusted by the Hosmer-Lemeshow test with significance set at P < .05. RESULTS: We found that hyponatremic recipients had a 6.26-fold higher risk for early death. There was a 9% reduced chance of death when the recipient serum sodium increased 1 unit. The chance of EGD3 to have early death was 18-fold higher than for EGD1 and there was a 13% increased risk for death for each unit of pRBC transfused. CONCLUSIONS: Donor total bilirubin, hyponatremia, massive transfusion, and EGD3 in the allocation graft should be observed for better results in the postoperative period.

Correlation between functional capacity and respiratory assessment of end-stage liver disease patients waiting for transplant.

INTRODUCTION: End-stage liver disease has metabolic complications associated with malnutrition, which involves a great loss of muscle mass. This complication can lead to changes in the diaphragm, which along with ascites may impair daily activities and result in global motor disability and physical inactivity of patients on the waiting list for liver transplantation. OBJECTIVES: This study sought to delineate the profile of candidates for liver transplantation while on the waiting list at the Clinical Hospital of State University Campinas (UNICAMP), and to assess and verify whether there is a correlation between functional status of the individuals tested using the 6-minute walk test (6MWT), pulmonary function test (PFT), and respiratory muscle strength with end-stage liver disease candidates for liver transplantation. METHODS: This study was carried out in the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, 6MWT, PFT, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP), and SF-36. RESULTS: Correlations were found between the respiratory variables 6MWT and PFT. The walked distance was correlated with MIP and MEP. There was no correlation between the 6MWT and the variables body mass index and age. CONCLUSION: Candidates for liver transplantation have decreased muscle strength, normal lung function, and impaired quality of life, mainly due to physical limitations. Functional status may be correlated with the respiratory assessment (muscle strength and pulmonary function test) in liver disease candidates for transplantation.

Effects of a respiratory physiotherapeutic program in liver transplantation candidates.

BACKGROUND: Candidates for liver transplantation may have malnutrition, fatigue, loss of muscle mass and function. The combination of these factors leads to overall physical disability and physical inactivity. OBJECTIVE: The aim of the study was to evaluate the effects of a respiratory physiotherapeutic program on liver transplantation candidates. METHOD: Forty-two patients were evaluated by respiratory muscle strength, surface electromyography of the rectus abdominis and diaphragm, and spirometry. We also applied the SF-36. The patients were divided into two groups: 12 randomly assigned to the control group and 5 in the intervention group. The intervention consisted of an explanatory and illustrative manual to be followed at home with diaphragmatic breathing exercises, diaphragmatic isometric exercise, Threshold IMT, lifting the upper limbs with a bat, and strengthening the abdominals. RESULTS: Significant difference was found between initial forced expiratory flow (FEF)25-75% (P = .042) and final FEF25-75 in the intervention group. The control group had significant difference (P = .036) in the diaphragm RMS between initial time and end time. In conclusion, the control group showed greater electrical activity of the diaphragm after 3 months. CONCLUSION: The intervention group benefited from the exercise, thus improving the FEF25-75%.

Evaluation of functional status, pulmonary capacity, body composition, and quality of life of end-stage liver disease patients who are candidates for liver surgery.

INTRODUCTION: Muscular weakness in combination with malnutrition can induce a global motor impairment and physical inactivity, adversely impairing the daily living activities and quality of life of end-stage liver disease patients who are candidates for liver transplantation. OBJECTIVES: To evaluate functional status, pulmonary capacity, body composition and quality of life in end-stage liver disease patients who are candidates for liver transplantation; to verify if there is a correlation between the functional variables of the individuals tested through the 6-minute walk test (6MWT) and covariables: pulmonary function test (PFP), quality of life and body composition. METHODS: This study was carried out at the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, quality of life questionnaire "Short Form 36" (SF-36), surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles, body composition assessment by electrical vioimpedance (BIA), 6MWT and PFP. RESULTS: Univariate analysis and Pearson's correlation found correlations between distance walked on 6MWT and QOL (P = .006 and P = .02) and TBW (P = .5 and P = .02). Pearson's correlation were found between respiratory variables of 6MWT, QOL, and PFP. CONCLUSION: The functional status may be correlated to body composition, quality of life and pulmonary capacity of patients with liver disease, candidates for transplantation.

Rhabdomyolysis as a clinical manifestation of association with ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in liver-transplanted patients: a case report and literature review.

BACKGROUND: Rhabdomyolysis is a syndrome characterized by impaired metabolic integrity of myocytes, causing the release of intracellular constituents into the circulation, and can be a serious side effect of drug intake. CASE REPORT: This report describes a unique case of rabdomyolysis secondary in which ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in a liver transplant patient was used. A 47-year-old male liver transplant recipient in 2009, who had hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive therapy (cyclosporine and sirolimus). The patient is currently in treatment for viral recurrence with pegylated interferon-α and ribavirin; he had a history of hypertriglyceridemia treated with ciprofibrate. He had development of severe and generalized myalgia and fever after the eighth application of pegylated interferon-α and increasing doses of cyclosporine. Laboratorial tests showed acute renal failure and significant increase in creatine kinase. Rhabdomyolysis secondary to interaction of fibrate-cyclosporine-pegylated interferon-α was postulated. CONCLUSIONS: Medical professionals should be aware of possible drug interactions and should monitor patients receiving these drugs.

Liver transplantation in a patient with clinical manifestations of cryptogenic cirrhosis: a case report of hepar lobatum as a primary liver condition.

BACKGROUND: This article reports a case of hepar lobatum, a peculiar and rare type of liver deformity, originally described in association with infectious or parasitic diseases and with malignancies. CASE REPORT: We have described a 42-year-old woman with this disorder, which was unrelated to the known conditions and referred for liver transplantation for having clinical manifestations of cirrhosis, portal hypertension, and impaired hepatic function. CONCLUSIONS: The observed histologic pattern suggests that hepar lobatum could be, in some patients, the effect of a primary process of hamartomatous origin involving the organ vascular supply.

Liver failure and the need for transplantation in 6 patients with hepatoportal sclerosis.

Hepatoportal sclerosis (HPS), first reported by Mikkelsen et al in 1965, is a pathologic condition that does not cause cirrhotic portal hypertension. The primary hepatic lesion in HPS is found in portal vein branches with preserved synthetic function. Rarely do patients with HPS need liver transplantation. The aim of this study was to describe the clinical and pathologic features of 6 HPS cases who underwent liver transplantation (OLT). From 2000 to 2008, 6 OLT candidates were diagnosed with HPS: 3 displayed bleeding varices and 4 ascites. Child-Pugh evaluation was class B (n = 4) or C (n = 2). The Model for End-stage Liver Disease scores were 18 (n = 2), 20 (n = 3), and 22 (n = 1). Cirrhosis resulted from presumed diagnoses of alcohol n = (1), autoimmune n = (2) or cryptogenic cirrhosis n = (3). On histologic examination, there was marked phlebosclerosis in all cases, including nonocclusive portal vein thrombosis (n = 3), intense portal fibrosis (n = 1), moderate portal fibrosis (n = 5), and uniform moderate sinusoidal dilatation without megasinusoid formation, but with ductal biliary proliferation and ductal biliary fibrosis in all cases. Cholestasis was observed in 1 and incomplete septal cirrhosis in 4 cases. None of the subjects showed histological features of the presumed underlying liver disease. The overall survival of this group was no different from that of other OLT patients. HPS causing hepatic failure may require liver transplantation. Fhlebosclerosis andportal fibrosis may contribute to the loss of hepatic synthesis leading to the need for hepatic transplant. Significant portal fibrosis and phlebosclerosis can contribute to hepatic parenchymal and posterior synthetic loss.