Recurrent alcohol-associated hepatitis is common and is associated with increased mortality.

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

Age, period and cohort effects on gastric cancer mortality in Spain, 1980-2021.

BACKGROUND: this study aimed to evaluate the effects of age, time period and cohort (A-P-C) on gastric cancer (GC) mortality in Spain from 1980 to 2021. METHODS: an ecological trend study was performed (with aggregated data obtained from the Spanish National Statistics Institute (INE). Joinpoint regression software was used to estimate rates by sex and age group (< 35, 35-64, > 64 years) and mortality trends. The National Cancer Institute A-P-C tools were used to assess the effects of age, time of death and birth cohort. RESULTS: GC mortality rates in Spain decreased significantly in both sexes. In the under-35 age group, rates were stable after an initial significant decline. In the 35-64 age group, the decline was more pronounced in males than in females. In the 65+ age group, rates fell significantly for both sexes, but more so for females than for males. The net drift and local drift also showed significant decreases across all age groups from 24 years onwards. GC mortality rates increased with age and decreased with calendar time and successive birth cohorts, regardless of sex. The ratio of age-specific rates between males and females increased with age, and birth cohort relative risk estimates followed a steady downward trend until the mid-1970s, after which the decline stabilized. The relative risk decreased for both sexes, with a more pronounced decrease in males. CONCLUSION: GC mortality rates in Spain have been decreasing over time and across successive birth cohorts, with a stabilizing trend observed for those under 35 years of age.

Investigating temporal patterns of colorectal cancer incidence in Spain: a comprehensive analysis of age, period and cohort effects, 1990-2019.

AIM: This study aimed to evaluate how age, period, and cohort (A-P-C) impact colorectal cancer (CRC) incidence in Spain from 1990 to 2019. METHOD: Using data from the Global Burden of Disease Study 2019, we used joinpoint analysis to identify long-term trends and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects. RESULTS: CRC incidence increased steadily in Spain from 1990 to 2019, with a more significant rise in males than in females. The age standardized rates rose from 84.9 to 129.3 cases per 100,000 in males and from 56.9 to 70.3 cases per 100,000 in females. Joinpoint analysis revealed distinct patterns for men and women: male incidence showed three phases (a surge until 1995, a slowdown until 2012, and a subsequent decrease) while female incidence showed a single increase until 2011 and then stabilized. Local drifts increased in all age groups over 45, with stability in males under 45 and a decrease in females aged 30-39. The risk of CRC increased with age, with males consistently having a higher risk than females. The risk of CRC increased over time for both men and women but at different rates. The risk for cohorts born in the early to mid-20th century peaked in the 1960s and remained stable until the late 1990s. CONCLUSION: The increasing incidence of CRC in Spain, with distinct patterns by gender and birth cohort, underlines the importance of preventive strategies adapted to temporal and demographic variations to address this public health challenge.

Characterizing Hepatitis Delta in Spain and the gaps in its management.

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated HDV prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial.

OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.

Regenerative nodular hyperplasia, portal vein thrombosis and primary myelofibrosis: an unusual triple association.

We report a case of a regenerative nodular hyperplasia with a portal vein cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis of the superior mesenteric vein. A thorough investigation resulted in a final diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2 gene.

Canalicular cholestasis induced by anabolic steroids.

Inappropriate use of anabolic steroids is increasing, usually by younger males in an illicit manner. This is a well-documented case of cholestatic hepatitis attributed to use of anabolic steroids for esthetic and/or athletic purposes.

Post-transfusion hyperhemolysis syndrome following gastrointestinal bleeding secondary to prehepatic portal hypertension.

Supportive transfusion represents a basic tool in the management of gastrointestinal (GI) bleeding. However, the use of hemoderivatives is not exempt from risks such as development of hemolysis. We report a case of post-transfusion hyperhemolysis syndrome in a female patient with prehepatic portal hypertension.

Hepatic veno-occlusive disease induced by Chinese medicinal herbs.

The potential hepatotoxic effects of products containing medicinal herbs, which are increasingly used without adequate control by health authorities, is well known. We report a case of toxic hepatic veno-occlusive disease (HVOD) presumably associated with the use of such herbal remedies.

Severe acute hepatitis and cold agglutinin-related hemolytic anemia secondary to prime infection with Epstein-Barr virus.

Epstein-Barr virus, a member of the Herpesviridae family, is responsible for the infectious mononucleosis clinical syndrome, which mainly includes the pharyngitis, fever, and lymphadenopathy triad after incubation for 30-50 days. The liver is involved in 80-90% of patients in a self-limiting transient manner, with jaundice being much more uncommon (5%). From a hematological standpoint it may manifest aplastic anemia, neutropenia, and thrombocytopenia. We report a case of infectious mononucleosis that included severe acute hepatitis and was associated with severe hemolytic anemia secondary to cold agglutinins. After exclusion of other etiologies, and given the clinical suspicion of the above association, which was later confirmed by lab tests, empiric therapy was initiated with antiviral agents (aciclovir + valganciclovir) and corticoids, which resulted in a progressive clinical improvement until complete remission. Therefore, we believe that this case report will reinforce the clinical evidence in support of the above combined therapy for serious infectious mononucleosis as a step prior to liver transplantation.

[Blood coagulation factor levels in candidates for liver transplantation: correlation with disease severity]. / Correlación entre concentraciones de factores de la coagulación en candidatos a trasplante hepático y gravedad de la enfermedad.

OBJECTIVE: To correlate blood coagulation factor levels with disease severity in cirrhotic patients evaluated as candidates for liver transplantation. MATERIAL AND METHOD: We included 87 patients (75.9% men) with a mean age of 54+/-9.4 years. Etiology and Child-Turcotte-Pugh (CTP) class were as follows: alcohol-related (36.8%), hepatitis C virus infection (35.6%), hepatitis B virus infection (11.5%) and other (16.1%); class A (13.8%), class B (40.2%) and class C (46%), respectively. The mean value of the Model for End-Stage Liver Disease (MELD) score was 14.5+/-5.9. Levels of factors II, V, VII, VIII, IX and X were compared between each CTP grade and with the MELD score. RESULTS: Except for factor VIII, all the clotting factors were reduced in our series (in particular factors II, V and VII) and deficiencies in these factors were closely related to CTP grade with statistical significance for stage C (p <0.05). We also found a marked inverse correlation between the MELD score and factors II, V, VII, IX and X values (p <0.05). CONCLUSIONS: A correlation was found between reduced levels of factors II, V, VII, IX and X in liver cirrhosis and the severity of liver disease.