PNPLA3 rs738409, age, diabetes, sex, and advanced fibrosis jointly contribute to the risk of major adverse liver outcomes in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing protein 3 ( PNPLA3 ) rs738409 variant is associated with steatotic liver disease and its progression. We examined the association between PNPLA3 and the development of major adverse liver outcomes (MALOs) and how nonmodifiable and modifiable conditions modify this relationship. APPROACH AND RESULTS: A total of 2075 adults with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the metabolic dysfunction-associated steatohepatitis Clinical Research Network (MASH CRN) studies and followed prospectively until death, transplant, or withdrawal of consent. One hundred four MALOs were recorded during an average of 4.3 years. PNPLA3 G-allele (Adj. sub-hazard ratio (sHR): 1.4, 95% CI: 1.07-1.8), advanced fibrosis (AF) (Adj. sHR: 7.8, 95% CI: 4.4-13.8), age >60 years (Adj. sHR: 2.9, 95% CI: 1.3-6.8), and type 2 diabetes mellitus (Adj. sHR: 2.8, 95% CI: 1.8-4.2) were associated with MALO. Among participants with AF, those carrying the G-allele displayed the highest cumulative incidence of MALO (85%) versus noncarriers (53%), p =0.03, and p -value for interaction <0.01. The strength of the association between PNPLA3 and MALO was statistically significantly greater among older than 60 years (sHR: 2.1, 95% CI: 1.5-2.8), women (sHR: 1.4, 95% CI: 1.1-1.9), and those with AF (sHR: 1.9, 95% CI: 1.5-2.4) or type 2 diabetes mellitus (sHR: 2.1, 95% CI: 1.5-2.8) as compared with their counterparts, p -value for interaction between PNPLA3 and each factor<0.01. CONCLUSIONS: The deleterious effects of PNPLA3 rs738409 on the risk of MALO are significantly worsened by AF, age, type 2 diabetes mellitus, and sex.

Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD.

BACKGROUND & AIMS: The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with non-alcoholic fatty liver disease (NAFLD) is not well-understood. We prospectively defined rates of progression to and regression from LSM-defined compensated advanced chronic liver disease (cACLD) and their associations with liver-related events (LREs). METHODS: Participants in the NASH Clinical Research Network-led NAFLD Database 2 and 3 studies were included. Progression to cACLD was defined as reaching LSM ≥10 kPa in participants with LSM <10 kPa on initial VCTE; regression from cACLD was defined as reaching LSM <10 kPa in participants with baseline LSM ≥10 kPa. LREs were defined as liver-related death, liver transplant, hepatocellular carcinoma, MELD >15, development of varices, or hepatic decompensation. Univariate and multivariable interval-censored Cox regression analyses were used to compare the cumulative LRE probability by LSM progression and regression status. RESULTS: In 1,403 participants, 89 LREs developed over a mean follow-up of 4.4 years, with an annual incidence rate for LREs of 1.5 (95% CI 1.2-1.8). In participants at risk, progression to LSM ≥10 or ≥15 kPa occurred in 29% and 17%, respectively, whereas regression to LSM <10 or <15 kPa occurred in 44% and 49%, respectively. Progressors to cACLD (≥10 kPa) experienced a higher cumulative LRE rate vs. non-progressors (16% vs. 4%, adjusted hazard ratio 4.0; 95% (1.8-8.9); p <0.01). Regressors from cACLD (to LSM <10 kPa) experienced a lower LRE rate than non-regressors (7% vs. 32%, adjusted hazard ratio 0.25; 95% CI 0.10-0.61; p <0.01). CONCLUSIONS: Change in LSM over time is independently and bi-directionally associated with risk of LRE and is a non-invasive surrogate for clinical outcomes in patients with NAFLD. IMPACT AND IMPLICATIONS: The prognostic value of change in LSM in patients with NAFLD is not well understood. In this large prospective study of patients with NAFLD and serial vibration-controlled transient elastography exams, baseline and dynamic changes in LSM were associated with the risk of developing liver-related events. LSM is a useful non-invasive surrogate of clinical outcomes in patients with NAFLD.

Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). New nomenclature and distinction of metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. We assessed the impact of different levels of alcohol consumption on SLD severity and its interaction with metabolic comorbidities. METHODS: Population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation) and U.S. (validation) cohorts. Controlled attenuation parameter (CAP≥275 dB/m) identified SLD. At least one cardiometabolic risk factor was required to define MASLD. Among MASLD patients, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as LSM≥8 kPa and at-risk MASH as FAST score≥0.35. RESULTS: The derivation cohort included 2,227 subjects with MASLD (9% reported low, 14% moderate alcohol consumption), and 76 cases with MetALD. Overall prevalence of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (OR=1.69 [95%CI 1.06-2.71]). CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease, in a similar magnitude to MetALD spectrum. IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently co-exist, but their joint effects on liver fibrosis remain uncertain. This study analyzes subjects form the general population with metabolic dysfunction-associated steatotic liver disease (MASLD) enrolled in Spain and U.S. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that patients with unhealthy metabolic status and MASLD have no safe limits of daily alcohol intake.

Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.

BACKGROUND & AIMS: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD. METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG). RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both). CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.

Effects of Food Insecurity on Hepatic Steatosis and Fibrosis in People With HIV.

BACKGROUND & AIMS: Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. METHODS: We examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥ 18 years on antiretroviral therapy, HIV RNA <200 copies/mL, and without other known liver diseases were screened for NAFLD (controlled attenuated parameter ≥263 decibels/meter) and advanced fibrosis (liver stiffness measurement ≥11 kilopascals) by vibration controlled transient elastography at 8 U.S. CENTERS: Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD and advanced fibrosis by FI status. RESULTS: Among 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 of participants (31%), including 97/348 with NAFLD (28%) and 18/41 with advanced fibrosis (44%). In multivariable analysis, FI was associated with lower odds of NAFLD (OR, 0.57; 95% CI, 0.37-0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR, 1.38; 95% CI, 0.65-2.90). We identified a significant interaction between FI and diabetes (P = .02) on fibrosis risk, with greater odds of fibrosis among food insecure PWH and diabetes (OR, 3.83; 95% CI, 1.15-12.73) but not among food insecure nondiabetics (OR, 1.12; 95% CI, 0.47-2.98). CONCLUSIONS: FI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, there is greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH.

Diagnostic Ability of Simple Noninvasive Blood Tests to Predict Increased Liver Stiffness in People Living With HIV and Steatotic Liver Disease.

INTRODUCTION: Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM). METHODS: We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <-1.455 and >0.675 for NFS). RESULTS: A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m 2 ) and 43% obese (body mass index ≥30 kg/m 2 ). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4 + T-cell count was 666 cells/mm 3 , 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF. DISCUSSION: FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist.

Role of Spleen Stiffness Measurement in the Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: Spleen stiffness measurement (SSM) correlates with the severity of portal hypertension. AIMS: We investigated the utility of SSM in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) for detecting cirrhosis, esophageal varices (EV), and high-risk EV. METHODS: 154 study participants with MASLD underwent simultaneous liver stiffness measurement (LSM) and SSM. 96 (62%) participants had an upper endoscopy (73 participants, i.e., 47% undergoing within a year). The diagnostic performance of SSM, as well as the BAVENO VII proposed SSM cutoffs (≥ 21 kPa, > 40 kPa, and > 50 kPa), was examined. RESULTS: The failure rate for SSM was 19% compared to 5% for LSM. An invalid SSM was statistically significantly associated with a higher body mass index, a larger waist circumference, and a lower fibrosis stage. The area under the receiver operating characteristics for SSM to diagnose cirrhosis, EV, and high-risk EV was 0.78 (95% CI 0.70-0.85), 0.74 (95% CI 0.61-0.84), and 0.82 (95% CI 0.75-0.98), respectively. SSM ≥ 21 kPa cutoff had a sensitivity > 96% for all three outcomes, with a positive predictive value (PPV) of 88% for cirrhosis. In contrast, SSM > 40 kPa and SSM > 50 kPa cutoffs had better diagnostic abilities for identifying EV, particularly high-risk EV (sensitivity of 100% and 93% with NPV of 100% and 96%, respectively). CONCLUSION: SSM has a higher failure rate in individuals who are non-cirrhotic or have a higher BMI, or larger waist circumference. Although useful for diagnosing NASH cirrhosis, SSM is most reliable in excluding EV and high-risk EV.

Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis.

BACKGROUND: There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). AIMS: This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. METHODS: Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. RESULTS: Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. CONCLUSIONS: Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.

Prevalence of steatotic liver disease, MASLD, MetALD and significant fibrosis in people with HIV in the United States.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD. AIMS: To assess the effects of this new nomenclature on the prevalence and distribution of different SLD categories in people with HIV (PWH) and identified factors associated with MASLD and clinically significant fibrosis (CSF). METHODS: PWH were prospectively enrolled from 9 US centres and underwent clinical evaluation and vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SLD was defined as CAP ≥ 263 dB/m, CSF as LSM of ≥8 kPa, and advanced fibrosis (AF) as LSM ≥ 12 kPa. The prevalence of SLD, MASLD, metabolic dysfunction and alcohol-associated liver disease (MetALD), ALD, cryptogenic (cSLD), CSF and AF were determined. Uni- and multivariate logistic regression models were used to assess factors associated with MASLD and CSF risk. RESULTS: Of 1065 participants, 74% were male, mean (SD) age 51.6 ± 11.9 years, 46% non-Hispanic Black and 74% with undetectable HIV RNA. The prevalence of SLD was 52%, MASLD 39%, MetALD 10%, ALD 3%, CSF 15% and AF 4%. Only 0.6% had cSLD. Black race was protective whereas obesity, ALT and AST levels were associated with increased risk of MASLD and CSF in MASLD. HIV or antiretroviral therapy did not affect MASLD risk. CONCLUSIONS: MASLD and MetALD are the dominant causes of SLD in PWH, affecting almost half. Application of the new nomenclature resulted in minimal change in the proportion of patients with MASLD who would have been diagnosed previously with NAFLD.

Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica / Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline

La enfermedad hepática grasa no alcohólica (EHGNA) es la causa más frecuente de hepatopatía crónica en nuestro medio y se prevé un incremento de su incidencia en los próximos años asociada al incremento de la obesidad y el síndrome metabólico. Esta guía de práctica clínica propone recomendaciones sobre el diagnóstico y en especial marcadores no invasivos, así como en el manejo y seguimiento de esta enfermedad. La intervención dietética basada en la dieta mediterránea y el cambio del estilo de vida constituyen el pilar del tratamiento de la EHGNA, pero aún falta por elucidar si la composición de la dieta puede influir en la mejoría de la enfermedad más allá de la pérdida de peso. El tratamiento con fármacos debe restringirse a los pacientes con esteatohepatitis y fibrosis significativa que no consiguen resolución de la esteatohepatitis después de una intervención con dieta y ejercicio físico durante un año. Nuevos fármacos aún en fases iniciales de desarrollo han demostrado ser superiores a placebo. Por último, el impacto de la EHGNA en la indicación de trasplante hepático, la viabilidad del injerto y la recidiva de EHGNA de novo tras el trasplante, así como el incrementado riesgo cardiovascular determinan todo el proceso peritrasplante hepático. Esta guía de práctica clínica se ha elaborado tras la I Reunión de Consenso sobre EHGNA con un panel de experto nacionales e internaciones en Sevilla y tienen como objetivo proponer recomendaciones basadas en la evidencia científica disponible para el manejo de estos pacientes

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville

Modelos pronósticos para la cirrosis hepática / Prognostic models for hepatic cirrhosis

Los modelos pronósticos representan un pilar importante en la evaluación de los pacientes con cirrosis hepática, sobre todo a la hora de tomar decisiones como el trasplante hepático. Los 2 modelos más utilizados al nivel mundial, el Child Pugh Turcotte y el Model for end stage liver disease (MELD), presentan ventajas y desventajas en su aproximación a los pacientes. El objetivo de este trabajo fue revisar estos modelos pronósticos utilizados en la enfermedad hepática terminal, así como comparar el modelo MELD y el Child Pugh Turcotte sobre la base del diseño, eficacia predictiva y aplicación practica. Se concluye que ambos modelos son útiles para predecir la mortalidad en los pacientes con cirrosis hepática y que se deben realizar futuras investigaciones para mejorar su poder discriminativo

The prognostic models are a significant pillar in assessment of patients presenting hepatic cirrhosis, mainly at moment to make a decision related to liver transplantation. The two more used models at international level, the Child Pugh Turcotte and the Model for end stage liver disease ( MELD) have advantages and disadvantages in its approximation to patients. The aim of present paper was to review these prognostic models used in the end-terminal liver disease, as well as to compare the above mentioned models on the base of the design, predictive effectiveness and practical application. We conclude that both models are useful to predict mortality in patients presenting with hepatic cirrhosis and also that more future researches must to be performed to improve its discriminatory power

Enfermedad hepática por depósitos grasos. Una perspectiva actual / [Nonalcoholic fatty liver disease. A current perspective].

A review about nonalcoholic fatty liver disease is presented, considering the updated aspects related to pathophysiology, diagnosis and management of this medical condition.

Tratamiento prolongado con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo / Prolonged treatment with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B

Las tasas de seroconversión del antígeno e alcanzadas con los antivirales actuales no sobrepasan el 35 por ciento. La combinación de inmunomodulador y antiviviral ha sido teóricamente la estrategia más aceptada en los últimos años; sin embargo, los resultados en la práctica clínica han sido contradictorios. Se realizó el presente trabajo para evaluar la eficacia y seguridad de un esquema de tratamiento prolongado durante 52 sem con interferón alfa-2b más lamivudina en pacientes con hepatitis crónica B y antígeno e positivo. Se estudiaron 46 pacientes asignados aleatoriamente: 23 recibieron 150 mg diarios de lamivudina por 4 sem, lamivudina más interferón alfa-2b (10 MU en días alternos) por 24 sem, seguido de lamivudina en la misma dosis y frecuencia hasta completar las 52 sem. Otros 23 recibieron 150 mg diarios de lamivudina por 4 sem y lamivudina más interferón alfa-2b (5 MU en días alternos) durante 52 sem. Se encontró que las tasas de seroconversión del antígeno fueron similares en ambos grupos. Una proporción significativa de pacientes con tratamiento combinado prolongado logró negativizar el ADN viral (52 por ciento frente al 26 por ciento, p=0,06) y el antígeno de superficie (48 por ciento frente al 26 por ciento, p=0,11), comparado con los controles. La mejoría en el índice de actividad histológica fue observada en el 48 por ciento de los pacientes tratados con tratamiento combinado prolongado frente al 22 por ciento de los controles (p=0,06). Se concluyó que el tratamiento prolongado de erferón y lamivudina durante 52 sem puede brindar beneficios clínicos en las tasas de pérdida sostenida del ADN viral, el antígeno de superficie y en el índice de actividad histológica.

The seroconversion rates of e antigen attained with the current antivirals do not exceed 35 percent. The combination of immunomodulator and antiviral has been theoretically the most accepted strategy in the last five years; however, the results in clinical practice have been contradictory. This paper is aimed at evaluating the efficacy and security of a treatment scheme prolonged for 52 weeks with alpha-2b interferon plus lamivudine in patients with e antigen positive chronic hepatitis B. 46 patients selected at random were studied: 23 received 150 mg of lamivudine daily during 4 weeks, lamivudine plus alpha-2b (10 MU every other day) for 24 weeks, followed by lamivudine in the same dose and frequency until completing the 52 weeks. Other 23 were administered 150 mg of lamivudine daily for 4 weeks plus alpha 2b interferon (5 MU every other day) during 52 weeks. It was found that the antigen seroconversion rates were similar in both groups. A marked proportion of patients with combined prolonged treatment proved to be negative to the viral DNA (52 percent vs. 26 p = 0.06) and the surface antigen (48 percent vs. 26 percent, p = 0.11) compared with the controls. The improvement in the histological activity rate was observed in 48 percent of the patients treated with combined prolonged treatment against 22 percent of the controls (p = 0.06) It was concluded that the prolonged treatment of interferon and lamivudine during 52 weeks may have clinical benefits on the rates of sustained viral DNA loss, surface antigen and the histological activity index.

Influencia de factores epidemiológicos en la progresión de la fibrosis en la hepatitis crónica C / Influence of epidemiological factors in the progression of fibrosis in chronic hepatitis C

Aproximadamente 80 por ciento de la hepatitis C evoluciona a la cronicidad. Factores como los epidemiológicos, virales y del huésped intervienen en la progresión de la enfermedad. Se describió el comportamiento de variables epidemiológicas asociadas a la hepatitis crónica C y se identificó la posible asociación de estas con la intensidad de la fibrosis. Se estudiaron 80 pacientes con hepatitis C. Se determinó la intensidad de la fibrosis por el sistema de puntuación METAVIR. Se agruparon en: ausencia o poca fibrosis (F0-F1) y fibrosis marcada (F2 a F4) buscando la posible asociación estadística con los factores epidemiológicos. Se halló asociación significativa entre el estimado de antigüedad de la infección, la vía de adquisición y la edad al contraerla con la intensidad de la fibrosis. La progresión de la hepatitis C puede estar determinada por algunos factores epidemiológicos que influyen de forma decisiva en la historia natural de la enfermedad

Bases fisiopatológicas de la insuficiencia hepática aguda / Physiopathological bases of acute liver failure

Se hace una revisión para explicar cómo influyen y la estrecha relación que tienen los diversos procesos celulares que ocurren en el tejido hepático, severamente dañado, y en la circulación mesentérica con las distintas alteraciones sistémicas que aparecen en la insuficiencia hepática aguda, síndrome clínico resultado de una necrosis hepática masiva que genera disfunción progresiva del órgano con la presencia de profundas alteraciones en sus funciones detoxificadora, metabólica, sintetizadora y excretora. La hipótesis de la masa crítica, así como la de las endotoxinas-citoquinas y sustancias vasoactivas explican de cierta forma los diferentes cambios moleculares que sustentan las bases fisiopatológicas de esta compleja entidad

Terapia de combinación secuencial con prednisona, lamivudina e interferón alfa-2b en pacientes con hepatitis crónica B y antígeno e positivo / Sequential combination therapy with prednisone, lamivudine and interferon alfa-2b for HBeAg-positive chronic hepatitis B

Introducción: A pesar del desarrollo de nuevos y potentes fármacos antivirales, los porcentajes de seroconversión del antígeno e alcanzados apenas sobrepasan el 35%. La inmunosupresión previa a la administración de antivirales ha sido investigada con resultados contradictorios. Evaluamos la eficacia y la seguridad de un esquema de inmunosupresión previa a la administración de lamivudina más interferón en pacientes con hepatitis crónica B y antígeno e positivo. Métodos: Un total de 44 pacientes fueron asignados aleatoriamente; 22 pacientes recibieron prednisona, 40 mg diarios durante 4 semanas, seguido de 2 semanas sin tratamiento, después lamivudina, 150 mg diarios durante 4 semanas, lamivudina más interferón alfa-2b (10 MU en días alternos) durante 24 semanas, seguido de lamivudina en la misma dosis y frecuencia para completar 58 semanas. Otros 22 pacientes recibieron el mismo esquema de tratamiento, pero sin inmunosupresión, hasta alcanzar las 52 semanas. Resultados: La combinación de seroconversión del antígeno e y concentraciones de ADN viral < 105 copias/ml, 24 semanas después de concluir el tratamiento, fue del 68% para el grupo de inmunosupresión previa y del 54% para los controles (p = 0,26). Un 45% del grupo de inmunosupresión logró una mejora del índice de actividad histológica frente al 23% de los controles (p = 0,10). Una proporción significativa de pacientes tratados con inmunosupresión previa alcanzó una mejoría de la inflamación (el 45 frente al 23%) y la fibrosis (el 50 frente al 23%), en comparación con el grupo control. Conclusiones: Nuestros resultados sugieren que no hubo diferencias estadísticas significativas en las tasas de seroconversión del antígeno e entre ambos esquemas de tratamiento; sin embargo, se observó una mejoría significativa en el índice de actividad histológica, inflamación y fibrosis en los pacientes tratados con inmunosupresión previa

Introduction: Despite the development of potent, new antiviral drugs, the percentage of HBeAg seroconversion is approximately 35%. Immunosuppression before antiviral administration has recently been investigated with contradictory results. We evaluated the safety and efficacy of lamivudine and interferon alfa-2b with prior immunosuppression with prednisone in patients with HBeAg-positive chronic hepatitis B (CHB). Methods: A randomized controlled study was conducted in a sample of 44 patients with HBeAg-positive CHB and persistently elevated alanine transferase (ALT) levels. The patients were distributed into two groups: 22 patients received prednisone 40 mg daily for 4 weeks, followed by 2 weeks without treatment, and lamivudine 150 mg daily for 4 weeks; lamivudine plus interferon alfa 2b (10 MIU every other day) was then administered for 24 weeks followed by continuous lamivudine 150 mg daily to complete 58 weeks. A further 22 patients received the same treatment regimen and duration, but without prednisone. Results: Virologic response defined as HBeAg seroconversion plus a decrease of serum HBV DNA < 105 copies/ml 24 weeks after concluding the treatment was observed in 68% of the patients receiving previous immunosuppression compared with 54% of the control group (p = 0.26). Forty-five percent of patients with prednisone priming showed histologic improvement compared with 23% of the control group (p = 0.10). A significant proportion of patient with previous immunosuppression showed improvement in necroinflammatory activity (45% vs 23%) and fibrosis (50 vs 23%) compared with the control group. Conclusions: Virologic response was clinically, but not statistically, superior in the group with prednisone priming. Histologic improvement was notable in the group with previous immunosuppression