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.

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study.

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC. Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria. Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria. Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.

Sonographic hepatorenal ratio: a noninvasive method to diagnose nonalcoholic steatosis.

PURPOSE: To evaluate the accuracy of the sonographic hepatorenal ratio (HRR) in the diagnosis and grading of nonalcoholic steatosis, using biopsy as the reference. METHODS: Ultrasound (US) and liver biopsy were performed in 42 patients with nonalcoholic fatty liver disease. Forty healthy volunteers without steatosis at US and without risk factors for nonalcoholic fatty liver disease were also studied. The HRR was obtained by dividing the mean brightness level of region-of-interest pixels in hepatic parenchyma by that in renal parenchyma. Needle biopsy samples (hematoxylin-eosin stained) were classified as mild (5-33% fatty infiltration), moderate (>33-66%), or severe (>66%) steatosis. Spearman coefficient was used to evaluate the correlation between HRR and steatosis grade, analysis of variance for differences between subgroups, and receiver operating characteristic curve analysis for sensitivity and specificity. RESULTS: Significant correlation was found between HRR and histologic steatosis (r = 0.80, p < 0.01). The HRR cutoff for predicting steatosis was ≥1.24 (sensitivity, 92.7%; specificity, 92.5%). The mean ± SD HRRs in controls and steatosis subgroups were control 1.09 ± 0.13, mild 1.46 ± 0.24, moderate 1.52 ± 0.27, severe 2.04 ± 0.3 and were significantly different from each other except between mild and moderate steatosis subgroups. CONCLUSIONS: The HRR is a noninvasive, objective, and simple method that could be used to diagnose and grade hepatic steatosis.

Assessment of portal venous index as a non-invasive method for diagnosing liver fibrosis in patients with chronic hepatitis C.

CONTEXT: Hepatitis C is an important cause of chronic liver disease worldwide. The grading of hepatic fibrosis in chronic hepatitis C is important for better clinical management. However, until now, liver biopsy is the only test accepted for this purpose, despite their contraindications and complications. New methods for non-invasive assessment of hepatic fibrosis are under investigation. One proposal is the Doppler ultrasound, as a non-invasive, widely available and inexpensive. OBJECTIVE: To compare Doppler parameters of portal vein in patients with chronic hepatitis C with a healthy control group and to correlate these parameters with fibrosis degree obtained by liver biopsy. METHODS: Fifty patients with chronic hepatitis C submitted to liver biopsy and 44 healthy controls had Doppler of the portal vein performed, with the calculation of the portal venous index. We conducted a comparison between the averages of the two groups of portal venous index. For the correlation between portal venous index and fibrosis was employed the Spearman test. RESULTS: There was a difference between the average portal venous index between controls (0.33 ± 0.07) and patients (0.23 ± 0.09) with P<0.001. No difference was observed between the portal venous index in patients with chronic hepatitis C who have significant fibrosis or not. The correlation between the portal venous index and fibrosis degree was reverse and moderate (r =-0.448 P<0.001). The area under the ROC curve was 78.4% (95% CI: 68.8% to 88%). The cutoff for the portal venous index was 0.28 with sensitivity of 73.5% and specificity of 71.1%. CONCLUSION: The portal venous index was useful in distinguishing healthy patients from patients with CHC. However, there was no significant difference in the quantification of degree of fibrosis.

Assessment of portal venous index as a non-invasive method for diagnosing liver fibrosis in patients with chronic hepatitis C / Emprego do índice venoso portal como método não-invasivo no diagnóstico de fibrose hepática em pacientes portadores de hepatite C crônica

CONTEXT: Hepatitis C is an important cause of chronic liver disease worldwide. The grading of hepatic fibrosis in chronic hepatitis C is important for better clinical management. However, until now, liver biopsy is the only test accepted for this purpose, despite their contraindications and complications. New methods for non-invasive assessment of hepatic fibrosis are under investigation. One proposal is the Doppler ultrasound, as a non-invasive, widely available and inexpensive. OBJECTIVE: To compare Doppler parameters of portal vein in patients with chronic hepatitis C with a healthy control group and to correlate these parameters with fibrosis degree obtained by liver biopsy. METHODS: Fifty patients with chronic hepatitis C submitted to liver biopsy and 44 healthy controls had Doppler of the portal vein performed, with the calculation of the portal venous index. We conducted a comparison between the averages of the two groups of portal venous index. For the correlation between portal venous index and fibrosis was employed the Spearman test. RESULTS: There was a difference between the average portal venous index between controls (0.33 ± 0.07) and patients (0.23 ± 0.09) with P<0.001. No difference was observed between the portal venous index in patients with chronic hepatitis C who have significant fibrosis or not. The correlation between the portal venous index and fibrosis degree was reverse and moderate (r =-0.448 P<0.001). The area under the ROC curve was 78.4% (95% CI: 68.8% to 88%). The cutoff for the portal venous index was 0.28 with sensitivity of 73.5% and specificity of 71.1%. CONCLUSION: The portal venous index was useful in distinguishing healthy patients from patients with CHC. However, there was no significant difference in the quantification of degree of fibrosis.

CONTEXTO: A hepatite C é uma importante causa de hepatopatia crônica no mundo. A avaliação do grau de fibrose hepática na hepatite C crônica é importante para o melhor manejo clínico. Entretanto, até o momento, a biopsia hepática é o único teste aceito para esta finalidade, apesar de suas contra-indicações e complicações. Novos métodos para avaliação não invasiva de fibrose hepática estão sendo pesquisados. Uma proposta é o ultrassom com Doppler, por ser um método não-invasivo, amplamente disponível e de baixo custo. OBJETIVO: Comparar os parâmetros Doppler da veia porta de portadores de hepatite C crônica com um grupo controle sadio e correlacionar estes parâmetros com os graus de fibrose obtidos por biopsia hepática. MÉTODOS: Cinquenta pacientes portadores de hepatite C crônica com biopsia hepática e 44 controles sadios foram submetidos ao Doppler da veia porta, com cálculo do índice venoso portal. Realizou-se a comparação entre as médias do índice venoso portal dos dois grupos. Para a correlação entre o índice venoso portal e os graus de fibrose empregou-se o teste de Spearman. RESULTADOS: Houve diferença entre a média do índice venoso portal entre os controles (0,33 ± 0,07) e os doentes (0,23 ± 0,09) com P<0,001. Não foi observada diferença do índice venoso portal entre os pacientes com hepatite C crônica que tem ou não fibrose significante. A correlação entre o índice venoso portal e o grau de fibrose foi inversa e moderada (r = -0,448 P<0,001). A área sob a curva ROC foi de 78,4% (IC 95%: 68,8%-88%). O ponto de corte para o índice venoso portal foi de 0,28 com sensibilidade de 73,5% e especificidade de 71,1%. CONCLUSÃO: O índice venoso portal foi útil em diferenciar pacientes sadios de pacientes portadores de hepatite C crônica. No entanto, não se encontrou diferença significante na quantificação dos graus de fibrose.

Dopplerfluxometria da veia hepática em pacientes com esteatose não alcoólica / Hepatic vein Doppler flowmetry in patients with nonalcoholic steatosis

OBJETIVO: Avaliar a correlação entre a dopplerfluxometria da veia hepática direita e o grau de esteatose, inflamação e fibrose à biópsia na doença hepática gordurosa não alcoólica. MATERIAIS E MÉTODOS: Foi realizada ultrassonografia com Doppler em 80 pacientes, sendo 40 portadores de doença hepática gordurosa não alcoólica, também submetidos à biópsia. Quarenta controles normais saudáveis, sem fatores risco para doença hepática gordurosa não alcoólica foram submetidos a ultrassonografia com Doppler. O padrão ao Doppler da veia hepática direita foi classificado em trifásico, bifásico e monofásico. Os espécimes de biópsia foram classificados conforme o grau de esteatose, inflamação e fibrose. RESULTADOS: O fluxo foi trifásico em 38 (95 por cento) dos controles e em 9 (56,3 por cento) dos pacientes com esteatose discreta, enquanto nos com esteatose acentuada o padrão foi monofásico em 60 por cento. Encontrou-se diferença significante na distribuição dos padrões ao Doppler (p < 0,01). Houve correlação negativa e significante entre o padrão ao Doppler da veia hepática direita e grau de esteatose (r = -0,57; p < 0,01). CONCLUSÃO: A alteração do padrão ao Doppler da veia hepática direita em pacientes com doença hepática gordurosa não alcoólica pode sugerir redução da complacência vascular consequente a infiltração gordurosa.

OBJECTIVE: To evaluate the correlation between right hepatic vein Doppler flowmetry and degree of steatosis, inflammation and fibrosis at biopsy in nonalcoholic fatty liver disease. MATERIALS AND METHODS: Doppler ultrasonography was performed in 80 patients divided into two groups as follows: 40 patients diagnosed with nonalcoholic fatty liver disease and also submitted to biopsy, and a control group including 40 healthy adults with no risk factor for nonalcoholic fatty liver disease. The Doppler waveform patterns of right hepatic vein were classified into triphasic, biphasic and monophasic. Biopsy specimens were classified according to the degree of steatosis, inflammation and fibrosis. RESULTS: Triphasic flow was observed in 38 (95 percent) patients of the control group and in nine (56 percent) patients with mild steatosis, whereas in patients with severe steatosis, the pattern was monophasic in 60 percent. A statistically significant difference was observed in the distribution of Doppler patterns (p < 0.01). A significant negative correlation between the Doppler waveform pattern of right hepatic vein and steatosis degree was observed (r = 0.57; p < 0.01). CONCLUSION: An abnormal Doppler waveform pattern of right hepatic vein in patients with nonalcoholic fatty liver disease may suggest the presence of decreased vascular compliance caused by fatty infiltration.