Hepatocellular Carcinoma Treatment With Sorafenib: Real-Life Evaluation of Prognostic Factors and a Practical Clue for Patient Management.

INTRODUCTION: Sorafenib chemotherapy is the first-line therapy for patients with hepatocellular carcinoma (HCC) in an advanced stage. The aim of this study was to evaluate prognostic factors of survival in HCC patients treated with sorafenib, in real-life clinical practice. MATERIAL AND METHODS: Retrospective study of HCC patients who initiated treatment with sorafenib, following assessment and indication from the multidisciplinary group. RESULTS: There were included 36 patients, mostly male (89%) and with a mean age of 65 years. The main etiologies were chronic hepatitis C (44%) and alcoholic liver disease (36%). Twenty patients (56%) were classified as Child-Pugh A and 16 patients (44%) as Child-Pugh B. Half of the patients group were staged as BCLC C and the remaining as BCLC B. Significant adverse events were observed in 15 patients (42%) and were associated with longer survival (21.5 vs. 3.2 months, p < 0.001). The most frequent adverse events were diarrhea and palmar-plantar syndrome. Median survival was 17.3 months for Child-Pugh A versus 3.2 months for Child-Pugh B patients (p = 0.001). Within Child-Pugh A, median OS was 21.5 months for BCLC B patients and 15.7 months for BCLC C patients (p = 0.001). DISCUSSION AND CONCLUSIONS: The main prognostic factors beyond Child-Pugh class and BCLC stage included the occurrence of significant adverse events. Being related to increased time of exposure to the drug, it points out the need of dose reducing instead of discontinuation whenever significant adverse events occur.

INTRODUÇÃO: O tratamento de primeira linha de doentes com carcinoma hepatocelular (HCC) em estadio avançado é a quimioterapia com sorafenib. O objetivo deste estudo foi avaliar os fatores de prognóstico de sobrevivência em doentes com HCC tratados com sorafenib, na prática clínica. MATERIAL E MÉTODOS: Estudo retrospetivo com inclusão dos doentes com HCC que iniciaram tratamento com sorafenib, após avaliação e decisão de grupo em reunião multidisciplinar. RESULTADOS: Foram incluídos 36 doentes, que eram em maioria do género masculino (89%) e com idade média de 65 anos. As principais etiologias eram a hepatite C crónica (44%) e a doença hepática alcoólica (36%). Vinte doentes (56%) foram classificados como Child-Pugh A e 16 doentes (44%) como Child-Pugh B. A amostra apresentava em metade dos casos estadio BCLC C e os restantes BCLC B. Quinze doentes (42%) desenvolveram efeitos adversos significativos, que se associaram com maior sobrevivência (21,5 vs 3,2 meses, p < 0,001). Os efeitos adversos mais frequentes foram diarreia e síndrome palmo-plantar. A sobrevivência global mediana foi de 6,8 meses (IC 95%, 3-10,6). A sobrevivência mediana foi de 17,3 meses nos doentes Child-Pugh A versus 3,2 meses nos casos Child-Pugh B (p = 0,001). Considerando os doentes Child-Pugh A, a sobrevivência mediana foi de 21,5 meses para o estadio BCLC B e 15,7 meses para o estadio BCLC C (p = 0,001). DISCUSSÃO E CONCLUSÕES: Os principais fatores prognósticos, além da classificação de Child-Pugh e do estadiamento BCLC, incluíram a ocorrência de efeitos adversos. Estes, relacionados com o tempo de exposição ao fármaco, assinalam a importância de uma estratégia de redução de dose em vez de descontinuação quando se manifestam efeitos adversos significativos.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy: A single center report of 8 cases.

This article describes cases of anti-tumor necrosis factor (TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis (AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Management of autoimmune hepatitis: Focus on pharmacologic treatments beyond corticosteroids.

In autoimmune hepatitis, patients who are intolerant or with toxicity experience, non-responders, relapsers or refractory are challenging. Non-standard drugs are being tried to preemptively avoid corticosteroid-related side effects. Prognosis and quality of life of life rely on treatment optimization. Recently, emergence of powerful immunosuppressive agents, mainly from liver transplantation, challenged the supremacy of the corticosteroid regime and promise greater immunosuppression than conventional medications, offer site-specific actions and satisfactory patient tolerance. Successes in experimental models of related diseases have primed these molecular interventions. We performed a literature review on alternative treatments. Azatioprine intolerance is the principal indication for mycophenolate use but it can be used as a front-line therapy. Cyclosporine A and tacrolimus have been tested for non-responders or relapsers. Rituximab may be used as salvage therapy. Anti-tumor necrosis factor-alpha agents may be used for incomplete responses or non-responders. Methotrexate is possibly an alternative for induction of remission and maintenance in refractory patients. Cyclophosphamide has been included in the induction regimen with corticosteroids. Ursodeoxycholic acid action is mainly immunomodulatory. Non-standard treatments are coming slowly to the attention, but its use should be cautious performed by experienced centers.

[Severe acute hepatitis C with spontaneous cure]. / Resolução espontânea de hepatite C aguda com insuficiência hepática.

Hepatitis C virus (HCV) is responsible for 20% of all cases of acute hepatitis. However, acute C infection isn't usually recognized in clinical practice, once most of the patients are asymptomatic and, in rare cases, the acute infection can progress to a fulminant form. In 40% of HCV infections, the mode of transmission persist unknown. Nosocomial transmission is, nowadays, recognized as a way of infection. Herein, we describe a female patient, with 54 years old, with an acute C hepatitis, symptomatic, with hepatic failure. She had no risky behaviours, just a previous hospital admission 5 weeks before. The patient was kept under surveillance with clinical improvement: at 10(th) week HCV viremia was negative.