A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. METHODS: A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. RESULTS: ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). CONCLUSION: ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population.

INTRODUCTION AND OBJECTIVES: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. MATERIAL AND METHODS: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. RESULTS: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. CONCLUSIONS: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

Cromomicose: relato de caso e revisão da literatura / Chromomycosis: case report and literature review

A cromomicose é uma micose profunda, crônica, com acometimento da pele e do subcutâneo. O fungo é encontrado na natureza nas plantas e no solo, sendo introduzido no organismo através de traumas ou ferimentos. A localização das lesões é, principalmente, nos membros inferiores, podendo também comprometer outras regiões. Os trabalhadores rurais são mais frequentemente acometidos por falta de proteção e exposição contínua. O objetivo deste relato foi apresentar um caso de cromomicose de evolução crônica, fazendo diagnóstico diferencial com outras doenças que causam a síndrome verrucosa (leishmaniose, esporotricose e tuberculose) e realizando breve revisão da literatura. Paciente do gênero masculino, 83 anos, branco, trabalhador rural, procurou Ambulatório de Dermatologia apresentando lesão vegetante, verrucosa, de base eritematosa, com distribuição linear, localizada no membro superior direito com evolução de 9 anos. As características da lesão sugeririam como hipóteses diagnósticas doenças que causam a síndrome verrucosa LECT (iniciais de leishmaniose, esporotricose, cromomicose e tuberculose). Para confirmação diagnóstica, foi realizada biópsia da lesão e exame histopatológico, que revelou presença de células arredondadas de cor castanho escuro em processo de reprodução binária, confirmando o diagnóstico de cromomicose. O paciente foi submetido ao tratamento com itraconazol e crioterapia combinados. A cromomicose possui diagnósticos diferencias em decorrência das características clínicas da lesão,sendo fundamentais, para sua confirmação diagnóstica, exames específicos.

Chromomycosis is a deep and chronic mycosis that affects the skin and the subcutaneous tissues. The fungus is found in nature, in plants and soil, being introduced into the body through trauma or injury. Lesions occur mainly on the lower limbs, but can also involve other regions. Rural workers are more frequently affected due to lack of protection and continuous exposure. The objective of this report was to present a case of chronic chromomycosis evolution, making differential diagnosis with other diseases that cause warty syndrome (leishmaniasis, sporotrichosis and tuberculosis) and performing a brief literature review. Male patient, 83 years old, white, farm laborer, sought the Dermatology Department presenting vegetative, verrucous lesion, with erythematous base, linear distribution, located on the right upper limb, with a 9-year progression. Lesion characteristics would suggest as diagnostic hypotheses diseases that cause warty syndrome LECT (acronym in Portuguese from leishmaniasis, sporotrichosis, chromomycosis and tuberculosis). For diagnostic confirmation, a biopsy and an histopathological examination were performed and revealed the presence of round, dark brown cells in binary reproduction process, confirming the diagnosis of chromomycosis. The patient was treated with itraconazole and cryotherapy combination. Chromomycosis has differential diagnosis due to the clinical characteristics of the lesion; therefore specific tests are fundamental to confirm the diagnosis.