Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

BACKGROUND AND AIMS: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. APPROACH AND RESULTS: We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. CONCLUSIONS: In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3 y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

A starry sky image result in a patient with active bleeding due to malignancy cause.

Hemostatic powders (HP) are increasingly used to address limitations in conventional endoscopic techniques for gastrointestinal bleeding. HP is a relatively recent addition to the arsenal of hemostatic endoscopic procedures (HEPs) for gastrointestinal bleeding (GIB) due to benign and malignant lesions, which all life-threatening conditions. HP acts as a mechanical barrier and/or promotes platelet activation and coagulation cascade. Malignancy causes comprise 1-5% of all non-variceal upper gastrointestinal bleeding (NVUGIB). UI-EWD (NexPowder) is composed of oxidized dextran and succinic anhydride, which is converted to an adhesive hydrogel upon contact with moisture. The resulting hydrogel cross-links within itself and with adjacent tissue to create a mechanical barrier to promote hemostasis. As it does not require clot formation to achieve hemostasis, UI-EWD does not require active bleeding. This provides it a potential role in prophylaxis, such as post-procedure or following primary hemostasis achieved with conventional endoscopic techniques. While UI-EWD is the newest development in hemostatic powders for clinical use, initial results are promising. We report the case of a 51-year-old male with epidermoid esophageal stenosing carcinoma recently diagnosed and locally advanced. Started treatment concurrent chemotherapy and radiotherapy, being necessary a nasogastric tube for parenteral nutrition. Our patient came to the emergency unit due to hematemesis which came from a pressure ulcer with active bleeding shown in gastroscopy exploration, withdrawing the tube and spraying onto the surface of the bleeding site UI-EWD until the bleeding lesion was completely covered with the powder, doing successful hemostasis confirmed by hemostasis until 5 minutes after the endoscopic treatment. HP is highly effective in patients with NVUGIB when used either in combination with or as rescue therapy. Rapid development of hemostatic powders and growing clinical expertise has established these agents as a valuable strategy in gastrointestinal bleeding.

Low phospholipid-associated cholelithiasis syndrome (LPAC), a not uncommon cause of biliary problems and hospital admissions.

BACKGROUND AND AIMS: Biliary diseases are a major source of morbidity and mortality for patients and a burden for the healthcare system. The genetic syndrome LPAC (low phospholipid-associated cholelithiasis) is a little known and rare entity whose treatment with bile salts avoids symptoms, admissions and the need for surgery. Our aim is to determine its incidence and characteristics in our center. METHODS: Prospective study between February 2021 and September 2022. LPAC was diagnosed if (at least two): onset of biliary problems <40 years of age, recurrence of symptoms after cholecystectomy, ultrasound image of hepatolithiasis (multiple echoic foci, comet-tail images, hepatolithiasis with acoustic shadow). Demographic, clinical, genetic (analysis of MDR3 gene mutations) and ultrasound characteristics were analyzed, as well as their incidence in hospital admissions for biliary causes. RESULTS: 36 patients with LPAC were identified. Of these, 6 were among 237 admissions for biliary causes in the previous 9 months, with an incidence of 2.5% (95%CI 1.17-5.41). By age subgroup, the incidence was 16.7% in those admitted <40 years and 9.1% in those <50 years. Considering women only, the incidence was 21% in those admitted <40 years and 15.8% in those <50 years. All patients remained asymptomatic after treatment with ursodeoxycholic acid and there were no new admissions. CONCLUSIONS: LPAC syndrome is not as uncommon as it may appear, especially in women <50 years of age admitted with biliary problems. Its correct diagnosis based on simple criteria would avoid a significant number of hospital admissions and unnecessary cholecystectomies.

Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.

A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis.

BACKGROUND AND AIMS: Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS: This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS: A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.

HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1.

BACKGROUND: The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)-monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. METHODS: We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. RESULTS: Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27-4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13-4.38; P = .020). CONCLUSIONS: The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.

Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España / Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain

INTRODUCCIÓN: GIDEON es un estudio internacional prospectivo, no intervencionista, que evaluó la seguridad de sorafenib en pacientes con carcinoma hepatocelular (CHC) no resecable en la práctica clínica diaria, incluidos pacientes Child-Pugh B. OBJETIVOS: Análisis de datos recogidos en España sobre seguridad y efectividad de sorafenib y los patrones de tratamiento. Métodos Se recogieron los datos demográficos y de la enfermedad, la dosis inicial usada, los acontecimientos adversos emergentes del tratamiento (AA) y las modificaciones de dosis a lo largo del seguimiento. Se valoraron la supervivencia global y el tiempo hasta la progresión de la enfermedad. La eficacia y la seguridad se analizaron en función de la clasificación Child-Pugh y la dosis inicial. RESULTADOS: Se incluyó a 143 pacientes de 19 hospitales españoles. El 24,5% eran pacientes Child-Pugh B. El 90,9% de los pacientes recibió una dosis inicial de 400 mg/12 h. En pacientes Child-Pugh A se modificó más frecuentemente la dosis y la duración del tratamiento fue más larga. La incidencia de AA y de aquellos relacionados con el fármaco fue similar en los pacientes Child-Pugh A y B, aunque los AA graves fueron más frecuentes en los pacientes Child-Pugh B. Los más frecuentes fueron diarrea, fatiga y eritrodisestesia palmo-plantar. La mediana de supervivencia global fue de 384 días, y superior en pacientes Child-Pugh A (593 vs. 211 días en Child-Pugh B); la mediana hasta la progresión de la enfermedad fue de 177 días, similar en ambos subgrupos. CONCLUSIÓN: El perfil de seguridad de sorafenib en pacientes españoles con CHC no resecable es independiente de la función hepática. El estado Child-Pugh no parece influir en el enfoque de dosificación de sorafenib ni en el tiempo hasta la progresión, pero sí parece ser un fuerte predictor de la supervivencia

INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. Methods Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival

[Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns of sorafenib use. Results of the international observational GIDEON trial in Spain]. / Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España.

INTRODUCTION: GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES: To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS: Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.