Background & Aims It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of ...weight loss through lifestyle modifications and changes in histologic features of NASH. Methods We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically. Results Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios = 1.1−2.0; P < .01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 58%) and a 2-point reduction in NAS (72 of 88 82%) than subjects who lost <5% of their weight ( P < .001). All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%−10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%. Conclusions A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses ≥10%.
Background & Aims
The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between ...changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI.
Methods
Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis.
Results
Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94‐0.99) than NFS, FIB‐4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84‐98) and 91% (95% CI, 81‐96) respectively.
Conclusions
Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.
Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system ...to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio OR = 2.75, 95% confidence interval CI 1.65‐4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005‐0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21‐44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83‐0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01‐0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) Conclusions: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875‐1887)
Population-based studies on the clinical course and prognosis of autoimmune hepatitis (AIH) from Caribbean countries are limited.
The aim of this study was to provide information regarding the ...clinical and laboratory findings, histological profile, treatments, and outcomes of patients with AIH with long-term follow-up in a tertiary referral center.
A retrospective study was performed at the National Institute of Gastroenterology in Havana, Cuba, by enrolling 82 patients with a well-documented, long-term clinical course of AIH. Clinical and laboratory findings, histological profiles, treatments, and outcomes were analyzed.
At diagnosis, 73 (89%) patients had AIH type 1, 84.1% were women, and their median age was 46.5 years (range, 17–79 years). The median follow-up period was 84 months (interquartile range, 12–276 months). Clinical onset was mild or subclinical in 72% of patients and asymptomatic in 12.2%. At diagnosis, the Hennes's median score was 6 (range, 3–8). Complications were seen in 44 (53.6%) patients, 42 (51.2%) with liver-related complications and 9 (10.9%) without liver-related complications. Cirrhosis was present at diagnosis in 32 (39%) patients. Cirrhosis was subsequently diagnosed in the other 28 patients who were not cirrhotic at diagnosis, over a median follow-up of 12 (IQR, 2-84) months. During follow-up, 6 patients died (7.3%). Cumulative survival at 5 and 10 years was 98.4% and 89%, respectively. A complete biochemical response was achieved in 79% of patients in a mean (SD) of 11.7 (11.6) months. Side effects due to treatment were reported in 76 (92.7%) patients, and no pretreatment factors were found to predict treatment response.
These Cuban patients with AIH had acceptable disease remission rate and a prompt treatment response. Although most patients had advanced-stage liver disease at diagnosis or developed during follow-up, the cumulative survival rate was high when patients were receiving and complying with treatment.
AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who ...were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor...
Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic ...parameters on disease progression in patients with advanced NAFLD.
We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n = 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes.
During a mean follow-up time of 5.5 years (range, 2.7–8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval CI, 86%–99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%–89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%–29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%–60% vs 6%, 95% CI, 2%–13%) or hepatocellular carcinoma (17%; 95% CI, 8%–31% vs 2.3%, 95% CI, 1%–12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%–18%) than cirrhosis (2%; 95% CI, 0%–6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%–23%) than cirrhosis (6%; 95% CI, 2%–15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcohol consumption was associated with these outcomes only in patients with cirrhosis.
Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.
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Abstract Background Autoimmune liver diseases (AILD) comprise a set of entities characterized by tissue damage as a result of the loss of self-tolerance. There are few reports of AILD from Caribbean ...countries. The aim of the study was to investigate the clinical patterns, laboratory findings, and immunological features, treatment responses, and prognoses of AILD in adult patients at a Cuban tertiary referral center. Methods A prospective study was conducted at the National Institute of Gastroenterology in Havana, Cuba from May 2012 to April 2016. Clinical, immunologic, and histologic features of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome, autoimmune cholangiopathy (AIC), and primary sclerosing cholangitis (PSC) were recorded. Response to therapy was assessed by serum ALT and bilirubin levels at 3, 6, 12, and 24 months after treatment-initiation. Results Of the 106 patients included in the study, 85.5% were female. The median age at presentation was 47 years. AIH was the most common AILD and was diagnosed in 60 patients (56.6%), 55 of whom had type 1 AIH. PBC was diagnosed in 22 (20.7%) patients, overlap syndrome in 16 (15%) patients, AIC in 5 (4.71%) patients, and PSC in 3 patients (2.8%). Most patients were symptomatic; 48 (45.2%) patients presented with liver cirrhosis and 14.5% with decompensated cirrhosis. Follow up of treatment was between 6 and 24 months. Prednisone monotherapy was used in 22 AIH patients (36.6%) and a combination of prednisone and azathioprine (AZA) was used in 28 (46.6%) AIH patients. Response to treatment was seen in 41 AIH patients (68.3%), 33 (55%) of whom had a complete response and 8 of whom (24.2%) relapsed after 12 months of maintenance therapy. No or incomplete response to treatment was seen in 18 (30%) patients. In 46 patients with autoimmune cholestasis, ursodeoxycholic acid was used as monotherapy in 25 (54.3%) patients. Conclusion The clinical profile of AILD in a sample of the Cuban population is similar to that reported in South areas. AIH was more frequent than PBC, and usually presented with advanced liver disease that responded poorly to treatment.
RESUMEN La hemocromatosis hereditaria es una enfermedad metabólica infrecuente que afecta primariamente al hígado, y que se caracteriza por un incremento de la absorción intestinal de hierro. Se ...presentó un paciente de 49 años de edad, evaluado en consulta externa, desde alrededor de dos años atrás, por: astenia, anorexia, artralgias e hiperpigmentación cutánea, asociada a hipertransaminasemia y seronegatividad para virus B y C. Los niveles de saturación de transferrina y ferritina evidenciaron la sobrecarga de hierro, y el estado homocigoto para la mutación C282Y confirmó la sospecha diagnóstica; se descartaron otras condiciones como: hepatitis crónica por virus B y C, esteatohepatitis no alcohólica, anemia hemolítica crónica, anemia sideroblástica, talasemia mayor, u otras enfermedades metabólicas que afectan al hígado. La biopsia hepática mostró hallazgos típicos de esta condición. Las flebotomías semanales fueron bien toleradas y se logró una mejoría clínica del paciente y de los parámetros de laboratorio.
RESUMEN Introducción: La Hiperplasia nodular linfoide gastrointestinal constituye una entidad infrecuente con manifestaciones clínicas diversas y con mayor frecuencia en la edad pediátrica. Objetivo: ...Caracterizar clínica, endoscópica e histológicamente a los pacientes pediátricos con hiperplasia linfoide de colon e íleon terminal diagnosticados en el Instituto de Gastroenterología. Material y Métodos: Se realizó un estudio descriptivo, transversal, en el periodo comprendido entre 2014 y 2016 en el Instituto de Gastroenterología. La muestra estuvo constituida por 50 pacientes, quienes cumplieron los criterios de inclusión y exclusión. Se evaluaron variables demográficas, clínicas, endoscópicas e histológicas, así como el comportamiento de la comorbilidad con enfermedades malignas, enfermedades inflamatorias intestinales, giardiosis, trastornos de la respuesta inmunohumoral y alergias alimentarias. Resultados: El sexo masculino, entre 7-10 años y el color de la piel blanca fueron los más frecuentes. El sangrado rectal fue el síntoma principal (62%) y la localización a nivel del íleon terminal en 69%, no se relacionó con enfermedad maligna, hubo tres pacientes con diagnóstico de hiperplasia linfoide de íleon terminal y colitis ulcerosa. El 74% presentó aspecto nodular por histología y 60% se le diagnosticó Giardia lamblia, en la evaluación inmunohumoral predominó los pacientes sin inmunocompromiso (78%), el Prick Test fue positivo en 60%, sobre todo, a la leche de vaca. Conclusiones: La manifestación clínica que predominó fue el sangrado rectal, endoscópicamente la localización en íleon y la forma nodular por histología. No encontramos comorbilidades con enfermedades malignas y fueron más frecuentes los trastornos alérgicos y parasitarios que las alteraciones inmunológicas.
Background & Aims The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between ...changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS,FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. Conclusions Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.
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