Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Treatment response and clinical event-free survival in autoimmune hepatitis: a Canadian multicentre cohort study.

BACKGROUND & AIMS: We sought to identify predictors of outcome for people living with autoimmune hepatitis (AIH). METHODS: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. RESULTS: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12-months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and immunoglobulin G (IgG) values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. CONCLUSION: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. IMPACT AND IMPLICATIONS: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, uses continuous measurements over follow-up, and our findings help inform risk stratification of patients. We provide evidence for treating clinicians, as well as those developing and evaluating new therapies, to seek evidence of good treatment response by keeping aminotransferase activity values within the reference range. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side-effects of treatment for patients.

Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders.

BACKGROUND AND AIMS: Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression. APPROACH AND RESULTS: A retrospective review was performed on a cohort of 58 patients (39 males) with DC/TBD who were prospectively evaluated at a single institute from 2002 to 2019. The median age at initial assessment was 18 (1.4-67.6) years, and median follow-up duration was 6 (1.4-8.2) years. Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non- TINF2 DC/TBD patients. Liver abnormality (defined at baseline assessment by laboratory and/or radiological findings) was present in 72.4% of patients with predominantly cholestatic pattern of liver enzyme elevation. Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the 6-year follow-up; this progression was mainly seen in patients with recessive or TINF2 -associated DC. Significant risk factors associated with progression included the presence of pulmonary or vascular disease. CONCLUSIONS: Our experience shows a high prevalence of cholestatic pattern of liver abnormality with progression to portal hypertension in patients with DC/TBD. Presence of pulmonary and/or vascular disease in patients with recessive or TINF2 DC was an important predictor of liver disease progression, suggesting the need for increased vigilance and monitoring for complications in these patients.

Distinct histological patterns in chronic hepatitis D with nucleos(t)ide analogue therapy.

Background: Chronic hepatitis delta virus (HDV) infection leads to a more severe hepatitis than hepatitis B virus (HBV) infection alone. Specific histological staining patterns have been described in HBV mono-infection, however this has not been extensively investigated in HDV co-infection. This study evaluated whether the use of nucleos(t)ide analogs (NAs) for concurrent HBV infection has an impact on the histological appearance of chronic HDV. Methods: Liver biopsies of all patients referred for management of HDV infection were reviewed and hepatitis-specific stains for HBV antigens were evaluated. Clinical and histological characteristics were compared between patients on and off-NA therapy. Results: 50 patients were included in our analysis, of which 26 (52%) were on NA therapy at the time of the biopsy. Overall, 8% stained for HBV core antigen and 86% stained for HBV surface antigen. On and off-NA groups had similar degrees of fibrosis and inflammation, however NA patients had an odds ratio of 7.15 for membranous staining and 0.13 for scattered granular staining (p = 0.001). No association was found with markers of disease severity or viral activity, with nonetheless a lower score of total inflammation noted in biopsies with a positive membranous stain (8.5 vs. 10.3 p = 0.04). Conclusion: In chronic HDV infection, patients treated with nucleos(t)ide analogs demonstrate a unique membranous staining pattern for hepatitis B surface antigen, which is not associated with HBV or HDV replicative activity. These findings may help improve the understanding of the role of HBV directed therapy in HDV pathophysiology. Highlights: Histological staining is associated with viral activity in chronic HBV, however this has been infrequently explored in HDV. In HDV, staining patterns differ based on HBV treatment status and do not appear to be associated with markers of viral activity.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Reversal of Clinically Significant Portal Hypertension After Immunosuppressive Treatment in a Patient With Sarcoidosis.

Sarcoidosis is a multisystemic disease which features non-necrotizing granulomas in lungs and other organs. Hepatic involvement in sarcoidosis varies between a mild asymptomatic disease and a progressive inflammatory granulomatous disease with or without cirrhosis. In this case presentation, we present a case of hepatic sarcoidosis complicated by clinically significant portal hypertension including splenomegaly and gastroesophageal varices successfully treated with immunosuppression to achieve portal hypertension reversal.

Shear wave elastography: How well does it perform in chronic hepatitis D virus infection?

Hepatitis delta virus (HDV) infection is associated with accelerated progression of liver disease to cirrhosis. Shear wave elastography (SWE) is a non-invasive evaluation method of liver fibrosis. Its performance in accurately characterizing HDV fibrosis compared to other noninvasive markers remains unknown. We assessed the performance of SWE in patients with chronic HDV, Hepatitis B (HBV) and Hepatitis C (HCV) infection. Cirrhosis was determined by histology or clinical data. Area under receiver operator characteristics (AUROC) was used to assess diagnostic performance in identifying cirrhosis by SWE in comparison with Fibroscan® (VCTE) and serologic tests of fibrosis. 158 patients with chronic hepatitis (HDV:44%, HBV: 46% and HCV: 29%) were evaluated. Cirrhosis was diagnosed in 28 (17.7%) patients. Mean noninvasive fibrosis measurements for the HBV/HCV and HDV groups, respectively, were as follows: APRI: 0.73 ± 1.08 and 1.3 ± 1.38; FIB-4: 1.90 ± 2.24 and 2.33 ± 2.24; VCTE: 8.9 ± 6.7 kPa vs 10.4 ± 5.3 kPa; SWE: 1.5 ± 0.2 m/s and 1.6 ± 0.2 m/s. The performance of SWE in detecting HDV-induced cirrhosis (AUROC 0.84, 95% CI 0.71-0.97) was slightly lower than in HBV/HCV induced disease (AUROC 0.88, 95% CI 0.81-0.96). For HDV patients, the performance of SWE was comparable to VCTE and slightly better than APRI and FIB-4 especially in APRI and FIB-4 indeterminate zones. The overall less accurate performance of noninvasive markers in HDV in comparison with HBV and HCV may be a result of significant hepatic inflammation in HDV.

Longitudinal Assessment of Bile Duct Loss in Primary Biliary Cholangitis.

INTRODUCTION: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression. METHODS: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC. RESULTS: Eighty-three patients were included, with ductopenia correlated to fibrosis stage at baseline. The cumulative incidence of severe ductopenia remained stable after 5 years, whereas fibrosis continually increased over time. Baseline AST-to-Platelet Ratio Index and elevated alkaline phosphatase >2 times the normal with abnormal bilirubin were associated with ductopenia progression. DISCUSSION: Bile duct injury does not seem to follow the same course as fibrosis in PBC.

Immune-Mediated Hepatitis During Immune Checkpoint Inhibitor cancer Immunotherapy: Lessons From Autoimmune Hepatitis and Liver Immunology.

Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.

Postprandial Plasma Lipidomics Reveal Specific Alteration of Hepatic-derived Diacylglycerols in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.

Long-Term Follow-Up into Adulthood of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis.

Studies on pediatric patients with primary sclerosing cholangitis (PSC) have been limited by short follow-up and inconsistent classification of pediatric patients with autoimmune hepatitis-sclerosing cholangitis overlap (AIC). We conducted a retrospective study of patients diagnosed with AIC or PSC during childhood with extension of follow-up into adulthood. Methods: We reviewed records of patients followed for PSC or AIC between 1998 and 2019 at a pediatric referral center. Features at diagnosis, biochemical and liver-related outcomes (cholangitis, liver transplant, and cirrhosis) were compared. Results: Forty patients (27 PSC, 13 AIC) were followed for 92 months on average (standard deviation 79 months) with extension into adulthood in 52.5%; 70% had associated inflammatory bowel disease (IBD). The proportion of patients with significant fibrosis and abnormal baseline liver tests (serum bilirubin and transaminase levels) were similar in both groups. One year postdiagnosis, 55% (15/27) of PSC patients had normal liver tests versus only 15% (2/13) in the AIC group (P = 0.02). During follow-up, more liver-related events occurred in the AIC group (69% versus 27%, hazard ratio [HR] = 3.7 [95% confidence interval (CI): 1.4-10] P = 0.01). Baseline elevated serum bilirubin levels (HR = 5.3 [95% CI: 1.7-16.9] P = 0.005) and elevated transaminase levels at 1 year (HR = 9.09 [95% CI: 1.18-66.7) P = 0.03) were predictive of liver-related events, while having IBD was not (HR = 0.48 (95% CI: 0.15-1.5) P = 0.22). Conclusions: Pediatric patients with AIC and PSC presented at a similar fibrosis stage, however, with a more severe hepatitis in AIC. In this cohort, AIC was associated with more liver-related events, primarily driven by a higher rate of cirrhosis compared with PSC; transplant rates were similar.

In decompensated cirrhosis, targeted albumin infusions did not improve an in-hospital composite outcome at 15 d.

SOURCE CITATION: China L, Freemantle N, Forrest E, et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med. 2021;384:808-17. 33657293.

Platelet count as a screening tool for compensated cirrhosis in chronic viral hepatitis.

BACKGROUND: Simple tools for clinicians to identify cirrhosis in patients with chronic viral hepatitis are medically necessary for treatment initiation, hepatocellular cancer screening and additional medical management. AIM: To determine whether platelets or other laboratory markers can be used as a simple method to identify the development of cirrhosis. METHODS: Clinical, biochemical and histologic laboratory data from treatment naive chronic viral hepatitis B (HBV), C (HCV), and D (HDV) patients at the NIH Clinical Center from 1985-2019 were collected and subjects were randomly divided into training and validation cohorts. Laboratory markers were tested for their ability to identify cirrhosis (Ishak ≥ 5) using receiver operating characteristic curves and an optimal cut-off was calculated within the training cohort. The final cut-off was tested within the validation cohort. RESULTS: Overall, 1027 subjects (HCV = 701, HBV = 240 and HDV = 86), 66% male, with mean (standard deviation) age of 45 (11) years were evaluated. Within the training cohort (n = 715), platelets performed the best at identifying cirrhosis compared to other laboratory markers [Area Under the Receiver Operating Characteristics curve (AUROC) = 0.86 (0.82-0.90)] and sensitivity 77%, specificity 83%, positive predictive value 44%, and negative predictive value 95%. All other tested markers had AUROCs ≤ 0.77. The optimal platelet cut-off for detecting cirrhosis in the training cohort was 143 × 109/L and it performed equally well in the validation cohort (n = 312) [AUROC = 0.85 (0.76-0.94)]. CONCLUSION: The use of platelet counts should be considered to identify cirrhosis and ensure optimal care and management of patients with chronic viral hepatitis.

Durable virological response and functional cure of chronic hepatitis D after long-term peginterferon therapy.

BACKGROUND: Hepatitis delta virus (HDV) infection is the most aggressive form of chronic viral hepatitis. Response rates to therapy with 1- to 2-year courses of pegylated interferon alpha (peginterferon) treatment are suboptimal. AIMS: To evaluate the long-term outcomes of patients with chronic hepatitis D after an extended course of peginterferon. METHODS: Patients were followed after completion of trial NCT00023322 and classified based on virological response defined as loss of detectable serum HDV RNA at last follow-up. During extended follow-up, survival and liver-related events were recorded. RESULTS: All 12 patients who received more than 6 months of peginterferon in the original study were included in this analysis. The cohort was mostly white (83%) and male (92%) and ranged in age from 18 to 58 years (mean = 42.6). Most patients had advanced but compensated liver disease at baseline, a median HBV DNA level of 536 IU per mL and median HDV RNA level of 6.86 log10 genome equivalents per mL. The treatment duration averaged 6.1 years (range 0.8-14.3) with a total follow-up of 8.8 years (range 1.7-17.6). At last follow-up, seven (58%) patients had durable undetectable HDV RNA in serum, and four (33%) cleared HBsAg. Overall, one of seven (14%) responders died or had a liver-related event vs four of five (80%) non-responders. CONCLUSIONS: With further follow-up, an extended course of peginterferon therapy was found to result in sustained clearance of HDV RNA and favourable clinical outcomes in more than half of patients and loss of HBsAg in a third.

Undiagnosed liver diseases.

The landscape of chronic liver disease has drastically changed over the past 20 years, largely due to advances in antiviral therapy and the rise of metabolic syndrome and associated non-alcoholic fatty liver disease (NAFLD). Despite advances in the diagnosis and treatment of a variety of liver diseases, the burden of chronic liver disease is increasing worldwide. The first step to addressing any disease is accurate diagnosis. Here, we discuss liver diseases that remain undiagnosed, either because they are difficult to diagnose or due to hepatic manifestations of an unrecognized systemic disease. Additionally, their underlying etiology may remain unknown or they represent previously uncharacterized and therefore novel liver diseases. Our goal is to provide a framework for approaching undiagnosed liver diseases which elude standard hepatic diagnostic work-up and whose patterns of disease are often overlooked.

Crohn's Disease after Proctocolectomy and IPAA for Ulcerative Colitis.

BACKGROUND: Proctocolectomy with IPAA is considered curative for ulcerative colitis. However, signs of Crohn's disease can develop postoperatively in some cases. OBJECTIVE: Our aim was to document the postoperative diagnosis of Crohn's disease, to identify potential preoperative predictive factors, and to review the evolution of patients on treatment. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted at a tertiary care center in Montreal, Canada. PATIENTS: A total of 301 patients underwent an IPAA for ulcerative colitis between 1985 and 2014. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of the postoperative diagnosis of Crohn's disease. RESULTS: During a median follow-up of 68 months, Crohn's disease was diagnosed at a median time of 77 months (8-270) in 38 patients (12.6%). The cumulative incidence of Crohn's disease was 7.5% at 5 years postoperatively and gradually increased to 17.7% and 33.0% at 10 and 20 years. The following predictive factors for Crohn's disease were observed on univariate analysis: current tobacco smoking at surgery (HR 3.56 (95% CI, 1.54-8.22)), suspicion of indeterminate colitis (HR 3.50 (95% CI, 1.69-7.24)), presence of mouth ulcers before surgery (HR 2.16 (95% CI, 1.03-4.53)), and age at diagnosis of ulcerative colitis (HR 0.94 (95% CI, 0.90-0.97)). Suspicion of indeterminate colitis (HR 3.18 (95% CI 1.46-6.93); p = 0.004) and age at diagnosis (HR 0.95 (95% CI, 0.91-0.99); p = 0.018) remained statistically significant on multivariate analysis. Postoperative inflammatory disease was controlled by medical therapy in most patients. Removal of the pouch was necessary in 16% of patients with Crohn's disease. LIMITATIONS: This was a retrospective single-center study. CONCLUSIONS: Diagnosis of Crohn's disease can occur at a distance from surgery with an increasing cumulative incidence over time. Preoperative predictive factors are few and should not determine candidacy for surgery. Therapeutic options are identical to those available for treatment of typical Crohn's disease and allow a favorable evolution in most patients. See Video Abstract at http://links.lww.com/DCR/B372. BROTE DE CROHN DESPUS DE UNA PROCTOCOLECTOMA CON ANASTOMOSIS DE RESERVORIO LEOANAL EN CASOS DE COLITIS ULCEROSA: ANTECEDENTES:La proctocolectomía con reservorio ileo-anal se considera curativa para la colitis ulcerosa. Sin embargo, signos de enfermedad de Crohn pueden desarrollarse después de la operación en algunos casos.OBJETIVO:Nuestro objetivo fue documentar el diagnóstico postoperatorio de la enfermedad de Crohn, identificar posibles factores predictivos preoperatorios y revisar la evolución de los pacientes con tratamiento.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro de atención terciaria en Montreal, Canadá.PACIENTES:301 pacientes portadores de un reservorio íleo-anal realizados por colitis ulcerosa entre 1985 y 2014.PRINCIPALES MEDIDAS DE RESULTADO:Acumulación de la incidencia en el diagnóstico postoperatorio de enfermedad de Crohn.RESULTADOS:Durante una media de 68 meses de seguimiento, la enfermedad de Crohn fué diagnosticada en un tiempo medio de 77 meses (8-270) en 38 pacientes (12,6%). La acumulación de incidencia de la enfermedad de Crohn fue del 7,5% a los 5 años después de la operación y aumentó gradualmente a 17,7 y 33,0% a los 10 y 20 años. Los siguientes factores predictivos para la enfermedad de Crohn se observaron en el análisis univariado: tabaquismo activo al momento de la cirugía (cociente de riesgo (HR) 3.56 (intervalo de confianza del 95% (IC) 1.54-8.22)), sospecha de colitis indeterminada (HR 3.50 (IC del 95% 1.69-7.24)), presencia de úlceras en la boca antes de la cirugía (HR 2.16 (IC 95% 1.03-4.53)) y edad al diagnóstico de colitis ulcerosa (HR 0.94 (IC 95% 0.90-0.97)). La sospecha de colitis indeterminada (HR 3.18 (IC 95% 1.46-6.93), p = 0.004) y la edad al momento del diagnóstico (HR 0.95 (IC 95% 0.91-0.99), p = 0.018) permanecieron estadísticamente significativos en el análisis multivariado. La reacción inflamatoria intestinal postoperatoria fue controlada con tratamiento médico en la mayoría de los pacientes. El retiro del reservorio íleo-anal fue necesario en 16% de los pacientes con enfermedad de Crohn.LIMITACIONES:Estudio retrospectivo de centro único.CONCLUSIONES:El diagnóstico de la enfermedad de Crohn puede ocurrir a distancia de la cirugía con la acumulación de incidencia creciente con el tiempo. Los factores predictivos preo-peratorios son pocos y no pueden determinar la candidatura para la cirugía. Las opciones terapéuticas son idénticas a las disponibles para el tratamiento de la enfermedad de Crohn típica y permiten una evolución favorable en la mayoría de los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B372. (Traducción-Dr. Xavier Delgadillo).

Hepatitis Delta: Prevalence, Natural History, and Treatment Options.

Half a century after its discovery, hepatitis delta remains a pertinent global health issue with a major clinical impact in endemic regions and an underestimated prevalence worldwide. Hepatitis delta virus infection follows a challenging clinical course and is responsible for significant liver-related morbidity. Although the only currently available treatment (pegylated interferon) does not provide consistent results, emerging therapeutic options are promising. This article explores the epidemiology, natural history, as well as current and potential therapeutic options for hepatitis delta virus infection.