Acute pancreatitis associated with boceprevir: a case report

Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30-50%. In an attempt to improve the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review / Drogas antirretrovirais e pancreatite aguda em pacientes com HIV/AIDS: existe alguma associação? Revisão da literatura

In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.

Em HIV-soropositivos, a incidência de pancreatite aguda pode chegar até 40% ao ano, o que é consideravelmente maior que na população geral, cuja incidência é de 2%. A partir de 1996, com a introdução da terapia antirretroviral combinada, conhecida pela sigla HAART (highly active antiretroviral therapy), o espectro de fatores nocivos ao pâncreas, como infecções oportunistas e uso de drogas para sua quimioprofilaxia, diminuiu consideravelmente. Análogos nucleotídeos e anormalidades metabólicas, esteatose hepática e acidose láctica despontaram como novas condições que podem acometer o pâncreas. A fim de avaliar o papel das drogas antirretrovirais para tratamento do HIV/AIDS na incidência elevada de pancreatite aguda nessa população, foi realizada revisão sistemática, com inclusão de artigos originais, relatos e séries de caso, cujos alvos de estudo eram pacientes HIV-soropositivos que evoluíram com pancreatite aguda após exposição a alguma das drogas que compõem o esquema antirretroviral. Essa associação foi confirmada após exclusão de outras possíveis etiologias e/ou recorrência do episódio de pancreatite aguda após reexposição ao fármaco suspeito. Zidovudina, efavirenz e os inibidores de protease são suspeitos de levar a uma pancreatite secundária à hiperlipidemia. Já os análogos nucleotídeos da transcriptase reversa, apesar de serem potentes inibidores da replicação viral, possuem grande espectro de efeitos colaterais, entre eles a mielotoxicidade e a pancreatite aguda. Didanosina, zalcitabina e estavudina já foram reportados como produtores de pancreatite crônica e aguda, tendo risco elevado com dose cumulativa. Didanosina com hidroxiureia, álcool ou pentamidina são fatores de risco adicionais, podendo induzir a uma pancreatite fatal, embora pouco frequente. Além disso, outras drogas usadas para profilaxia de doenças oportunistas relacionadas à AIDS, como sulfametoxazol-trimetoprima e pentamidina, podem produzir pancreatite necrotizante. Apesar das comorbidades que podem levar ao acometimento pancreático na população com HIV/AIDS, pancreatite medicamentosa desencadeada por drogas antirretrovirais sempre deve ser considerada no diagnóstico diferencial desses pacientes que se apresentam com dor abdominal e elevação das enzimas pancreáticas.

Acute pancreatitis associated with lamivudine therapy for chronic B hepatitis

Hyperamylasemia is a common complication during lamivudine use. We report a case of a pancreatitis following lamivudine therapy. A careful monitoring of amylase levels during treatment with lamivudine is discussed, mainly in the first weeks, considering the cost of this exam and further complication.

Induction of acute and chronic pancreatitis with the use of the toxin of the scorpion Tityus serrulatus: experimental model in rats

We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected IV in rats, in a single dose of 0,5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection; hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an intersting finding: the dose used preserved the animals from death and allowed the safe follow-up ot the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease.

La dieta hiperlipidica cronica intensifica la pancreatitis aguda inducida por ceruleina en la rata / Cerulein-induced acute pancreatitis enhanced by chronic hyperlipidic diet in the rat

El modelo experimental de pancreatitis aguda (PA) inducido por ceruleína (CR) está caracterizado por un significativo aumento de la lipasa sérica, edema inersticial pancreático, observación poco frecuente de cariorrexis y aparición de vacuolas acinares. Ratas Wistar macho adultas fueron alimentadas por una dieta hiperlipídica (lípidos al 45 por ciento) durante 6 semanas, usando como control ratas con dieta normolipídica (lipidos 5 por ciento). Se indujo una PA mediante una dosis única de CR intraperitoneal de 50 mugr/Kg. El incremento de la lipasa sérica fue similar en ambos grupos tratados con CR (dieta control e hiperlipídica). Por otra parte se comprobó incremento del edema intersticial, de la cariorrexis y fundamentalmente del grado de vacuolización de las células acinares con respecto al grupo control. Se concluye que la dieta hiperlipídica administrada en forma crónica intensifica las lesiones histopatológicas de la PA inducida por CR.

Experimental chronic interstitial pancreatitis induced by scorpion toxin in rats

Os efeitos do veneno de escorpiäo no trato gastrointestinal foram investigados no homem e em animais de experimentaçäo. O fluxo pancreático e o conteúdo enzimáticos säo aumentados por TsTX, o veneno purificado do escorpiäo Tityus serrulatus. Neste estudo, ratos machos receberam dose única intravenosa de TsTX. Eles foram sacrificados 20 dias após e o pâncreas foi removido. Estudos histopatológicos mostraram fibrose intersticial, infiltrado mononuclear, atrofia acinar e dilataçäo ductular. Também foram vistos, se bem que menos freqüentemente, infiltrado eosinofílico, hiperplasia ductular e densa secreçäo eosinofílica em ductos alargados. Todas as lesöes eram multifocais. Hiperplasia de ilhotas e nesidioblastose também foram observadas

Nesidioblastosis associated with chronic experimental pancreatitis produced by a scorpion toxin, tityustoxin, in rats

Tityustoxin (TsTx), the purified venom of the Brazilian scorpion Tityus serrulatus, was inected intravenously (50 microng/Kg) into rats, producing a typical picture of chronic pancreatitis after 20 days. Nesidioblastosis, a lesions characterized by hyperplasia of the islets of Langerhans, was also detected in a high percentage (40%) of animals. TsTx-induced pancreatitis may be a useful model for the study of nesidioblastosis in laboratory animals