Pirfenidone use in fibrotic diseases: What do we know so far?

BACKGROUND: Pirfenidone has demonstrated significant anti-inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti-inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro-inflammatory cytokines, apoptosis, and fibroblast activation. OBJECTIVE: To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. FINDINGS: Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. CONCLUSION: Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

Geographic disparities in access to liver transplant for advanced cirrhosis: Time to ring the alarm!

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS: In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS: Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION: Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING: National Institutes of Health and US Department of Veterans Affairs.

Hepamet Fibrosis Score in Nonalcoholic Fatty Liver Disease Patients in Mexico: Lower than Expected Positive Predictive Value.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been associated with different negative outcomes in the presence of advanced fibrosis. The Hepamet Fibrosis Score (HFS), a recently described noninvasive score, has shown excellent performance for the detection of advanced fibrosis. The aim of this study was to assess its performance in a Mexican population with NAFLD. METHODS: This was a retrospective cross-sectional study performed in 222 patients with biopsy-proven NAFLD, of whom 33(14%) had advanced fibrosis. We retrieved clinical data from each patient's medical record to compute the HFS, the NAFLD Fibrosis Score (NFS), and the Fibrosis-4 (FIB-4), and assess their performance. RESULTS: When considering the models as continuous variables, the area under the receiving operating characteristics curve of the HFS(0.758) was not different from that of the NFS(0.669, p = 0.09) or FIB-4(0.796, p = 0.1). The HFS had a sensitivity, specificity, positive and negative predictive values of 76.7% (95% CI 57.7-90.1), 90.1% (95% CI 85-93.9), 36.7% (95% CI 19.9-56.1), and 94.3% (95% CI 88.5-97.7), respectively. Indeterminate results (i.e., gray area) were more common with FIB-4 and HFS when compared with NFS [139(63%) and 122(55%) vs 80(36%), p < 0.001]. The variables that were associated with misclassification using the HFS were diabetes [OR 3.40 (95% CI 1.42-8.10), p = 0.006] and age [OR 1.06 (95% CI 1.01-1.11), p = 0.01]. CONCLUSION: The HFS showed sensitivity and specificity similar to that reported in the original publication; however, the positive predictive value was 36.7% at a pretest probability of 14%. The role of the HFS in prospective studies and in combination with other methods should be further explored.

Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study.

BACKGROUND AND AIMS: Pirfenidone (PFD), an oral antifibrotic drug, has been authorized by the EMA and FDA for treatment of idiopathic pulmonary fibrosis. Few studies have addressed its use in advanced liver fibrosis (ALF). We evaluated a prolonged-release formulation (PR-PFD) plus standard of care on disease progression in ALF. METHODS: 281 ALF patients from 12 centers receiving PR-PFD (600 mg bid) were screened; 122 completed 1 year of treatment. Additionally, 74 patients received only standard of care regimen. Average age was 64 ± 12 years, 58% female. 43.5% had fatty liver disease (NAFLD), 22.5% viral hepatitis C (VHC), 17% autoimmune hepatitis (AIH), and 17% alcoholic liver disease (ALD). Baseline fibrosis was F4 in 74% and F3 in 26%. Antifibrotic effects were assessed by transient elastography (Fibroscan®) and Fibro Test® (FT); Cytokines and PFD plasma levels were tracked and quality of life evaluated. RESULTS: We found a significant reduction in fibrosis in 35% of PR-PFD patients and only in 4.1% in non PR-PFD patients. Child-Pugh score improved in 29.7%. Biochemical values remained stable; 40.6% and 43.3% decreased ALT or AST, respectively. TGFß1 (pg/mL) levels were lower in PFD-treated patients. PFD serum concentration (µg/mL) was higher (8.2 ± 1.7) in fibrosis regression profile (FRP) patients compared to fibrosis progression profile (FPP) patients (4.7 ± 0.3 µg/mL, p < 0.01). 12% reported transient burning or nausea and 7% photosensitivity. Quality of life (Euro-Qol scale) improved from 62 ± 5 to 84 ± 3 (p < 0.001) and from 32 ± 3 to 42 ± 2 (p < 0.008) (FACIT scale). CONCLUSIONS: PR-PFD is efficacious and safe in ALF and associated with promising antifibrotic effects. TRIAL REGISTRATION: Clinical trial number: NCT04099407.

Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression.

Noninvasive methods for liver disease diagnoses offer great advantages over biopsy, but they cannot be utilized in all cases. Therefore, specific indicators for chronic liver disease management are necessary. The aim was to assess the production of insulin-like growth factor-binding proteins (IGFBPs) 1-7 and their correlation with the different stages of fibrosis in chronic hepatitis C (CHC). A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized by FibroTest® and/or FibroScan®. Serum concentrations of IGFBPs 1-7 were determined through multiple suspension arrangement array technology. Significant differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. Logistic regression models were performed to assess the association between the IGFBPs and fibrosis stages. The association was determined utilizing odds ratios (ORs), and receiver operating characteristic (ROC) curves were constructed to distinguish the IGFBPs in relation to the diagnosis of fibrosis. IGFBP-1 and IGFBP-7 concentrations were higher in CHC than in the healthy individuals, whereas IGFBP-3, IGFBP-5, and IGFBP-6 were downregulated in the patients. An apparent increase of all the IGFBPs was found at fibrosis stage F4, but with different regulations. IGFBP-2, -4, -6, and -7 had the best OR, showing the relation to fibrosis progression. The ROC curves showed that IGFBP-7 was the only protein that distinguished F1 from F3 and F2 from F3. IGFBPs participate in liver fibrosis progression and could be employed as circulating novel protein panels for diagnosis and as possible therapeutic targets in liver fibrosis progression.

Obesity in the Liver Transplant Setting.

The obesity epidemic has resulted in an increased prevalence of obesity in liver transplant (LT) candidates and in non-alcoholic fatty liver disease (NAFLD) becoming the fastest growing indication for LT. LT teams will be dealing with obesity in the coming years, and it is necessary for them to recognize some key aspects surrounding the LT in obese patients. Obesity by itself should not be considered a contraindication for LT, but it should make LT teams pay special attention to cardiovascular risk assessment, in order to properly select candidates for LT. Obese patients may be at increased risk of perioperative respiratory and infectious complications, and it is necessary to establish preventive strategies. Data on patient and graft survival after LT are controversial and scarce, especially for long-term outcomes, but morbid obesity may adversely affect these outcomes, particularly in NAFLD. The backbone of obesity treatment should be diet and exercise, whilst being careful not to precipitate or worsen frailty and sarcopenia. Bariatric surgery is an alternative for treatment of obesity, and the ideal timing regarding LT is still unknown. Sleeve gastrectomy is probably the procedure that has the best evidence in LT because it offers a good balance between safety and efficacy.

EVALUATION OF THE ROYAL FREE HOSPITAL CIRRHOSIS GLOMERULAR FILTRATION RATE FORMULA IN HISPANIC PATIENTS WITH CIRRHOSIS: AN EXTERNAL VALIDATION.

BACKGROUND AND AIMS: Glomerular filtration rate (GFR) measurement in patients with liver cirrhosis (LC) is the ideal method for adequate evaluation of kidney function. However, it is invasive, costly, and not widely accessible. Moreover, GFR estimation in patients with cirrhosis has been inaccurate. The aim of the present study was to evaluate and validate the recently described Royal Free Hospital (RFH) formula in a Hispanic cohort of patients with LC and compare it with other formulas, including the CKD-EPI cystatin C equation. METHODS: GFR was measured through the renal clearance of Tc-99m DTPA; it was cross-sectionally evaluated and compared with GFRs that were estimated utilizing the following formulas: RFH, Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease-6, CKD-EPI cystatin C, CKD-EPI Creatinine, and CKD-EPI Cystatin C-Creatinine. RESULTS: We included 76 patients (53% women). The mean measured GFR in the entire cohort was 64 ml/min/1.73m2; 54% of the patients had a GFR < 60 ml/min/1.73 m2 at the time of evaluation. The RFH formula and the CKD-EPI cystatin C formula showed the best performance, with a p30 of 62% and 59%, respectively. All formulas performed poorly when GFR was < 60 ml/min/1.73 m2. CONCLUSIONS: The RFH formula showed a better performance than the other formulas based on serum creatinine in a Hispanic population with LC. There was no difference in performance between the RFH formula and the CKD-EPI cystatin C formula.

Evaluation of the royal free hospital cirrhosis glomerular filtration rate formula in hispanic patients with cirrhosis: an external validation

Abstract Background and Aims Glomerular filtration rate (GFR) measurement in patients with liver cirrhosis (LC) is the ideal method for adequate evaluation of kidney function. However, it is invasive, costly, and not widely accessible. Moreover, GFR estimation in patients with cirrhosis has been inaccurate. The aim of the present study was to evaluate and validate the recently described Royal Free Hospital (RFH) formula in a Hispanic cohort of patients with LC and compare it with other formulas, including the CKD-EPI cystatin C equation. Methods GFR was measured through the renal clearance of Tc-99m DTPA; it was cross-sectionally evaluated and compared with GFRs that were estimated utilizing the following formulas: RFH, Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease-6, CKD-EPI cystatin C, CKD-EPI Creatinine, and CKD-EPI Cystatin C-Creatinine. Results We included 76 patients (53% women). The mean measured GFR in the entire cohort was 64 ml/min/1.73m2; 54% of the patients had a GFR < 60 ml/min/1.73 m2 at the time of evaluation. The RFH formula and the CKD-EPI cystatin C formula showed the best performance, with a p30 of 62% and 59%, respectively. All formulas performed poorly when GFR was < 60 ml/min/1.73 m2. Conclusions The RFH formula showed a better performance than the other formulas based on serum creatinine in a Hispanic population with LC. There was no difference in performance between the RFH formula and the CKD-EPI cystatin C formula.

Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH).

Alcohol-related liver disease (ALD) is a major cause of advanced chronic liver disease in Latin-America, although data on prevalence is limited. Public health policies aimed at reducing the alarming prevalence of alcohol use disorder in Latin-America should be implemented. ALD comprises a clinical-pathological spectrum that ranges from steatosis, steatohepatitis to advanced forms such as alcoholic hepatitis (AH), cirrhosis and hepatocellular carcinoma. Besides genetic factors, the amount of alcohol consumption is the most important risk factor for the development of ALD. Continuous consumption of more than 3 standard drinks per day in men and more than 2 drinks per day in women increases the risk of developing liver disease. The pathogenesis of ALD is only partially understood and recent translational studies have identified novel therapeutic targets. Early forms of ALD are often missed and most clinical attention is focused on AH, which is defined as an abrupt onset of jaundice and liver-related complications. In patients with potential confounding factors, a transjugular biopsy is recommended. The standard therapy for AH (i.e. prednisolone) has not evolved in the last decades yet promising new therapies (i.e. G-CSF, N-acetylcysteine) have been recently proposed. In both patients with early and severe ALD, prolonged abstinence is the most efficient therapeutic measure to decrease long-term morbidity and mortality. A multidisciplinary team including alcohol addiction specialists is recommended to manage patients with ALD. Liver transplantation should be considered in the management of patients with end-stage ALD that do not recover despite abstinence. In selected cases, increasing number of centers are proposing early transplantation for patients with severe AH not responding to medical therapy.

Changes in Cerebral Hemodynamics in Patients With Cirrhosis After Liver Transplantation.

Improvement in cognitive function after orthotopic liver transplantation (LT) has been demonstrated in the acute setting immediately after LT and in acute liver failure. However, the longterm changes in cerebral hemodynamics after LT remain unexplored. Therefore, we aimed to evaluate the longterm changes in cerebral hemodynamics of patients with cirrhosis after LT. In this prospective cohort study, we performed transcranial Doppler ultrasonography (TCD) measuring the pulsatility index (PI), resistance index (RI), and breath-holding index (BHI) to evaluate cerebrovascular structural integrity and reactivity, respectively, in both middle cerebral arteries before and after LT. Neuropsychometric tests and West-Haven criteria were used for hepatic encephalopathy (HE) characterization. Interleukin 6 and tumor necrosis factor α plasma levels were measured. Descriptive statistics and Wilcoxon's test were used. There were 27 patients who were included. Median follow-up after LT was 6 months, mean age before LT was 46.3 ± 10.3 years, the main etiology was hepatitis C virus (59%), and most of the patients were Child-Pugh B (15/27). Model for End-Stage Liver Disease (MELD) score was 16 ± 7.5, MELD-Na was 19.3 ± 7.1, Psychometric Hepatic Encephalopathy Score was -3.48 ± 3.66, and critical flicker fusion (CFF) was 40.28 ± 5.70 Hz. Before LT, 17/27 patients had HE and 11/27 ascites. A decrease of 20.8% and 13.5% in PI and RI was observed after LT (P < 0.001, both), together with an increase in BHI (32.4%, P = 0.122). These changes in cerebral hemodynamics paralleled those in systemic inflammation. Clinical improvement in cognition was observed in all patients with overt HE after LT. In conclusion, these results show a significant improvement in cerebral hemodynamics after LT, obtained through TCD, indicating less arterial cerebral vasoconstriction together with a decrease in systemic inflammation. Changes in cerebral vasoconstriction can be the basis for the improvement in cognitive function after LT in the long term.

Fibroblast growth factor 21 is an early predictor of acute-on-chronic liver failure in critically ill patients with cirrhosis.

Acute-on-chronic liver failure (ACLF) develops in acute decompensation (AD) of cirrhosis and shows high mortality. In critically ill patients, early diagnosis of ACLF could be important for therapeutic decisions (eg, renal replacement, artificial liver support, liver transplantation). This study evaluated fibroblast growth factor 21 (FGF21) as a marker of mitochondrial dysfunction in the context of ACLF. The study included 154 individuals (112 critically patients and 42 healthy controls) divided into a training and a validation cohort. In the training cohort of 42 healthy controls and 34 critically ill patients (of whom 24 were patients with cirrhosis), levels of FGF21, interleukin (IL) 6, and IL8 were measured. In the validation cohort of 78 patients with cirrhosis, 17 patients were admitted with or developed ACLF during follow-up and underwent daily clinical and nutritional assessment. Levels of FGF21 were higher in critically ill patients, especially in patients with cirrhosis admitted to the intensive care unit (ICU). Moreover, FGF21 as well as IL6 and IL8 levels were higher in patients with ACLF, but they did not increase with the severity of ACLF. Interestingly, in the validation cohort, FGF21 was also elevated in the patients who developed ACLF in the next 7 days. In these patients, FGF21 levels were an independent predictor of ACLF presence and development in multivariate analysis together with Child-Pugh score. FGF21 levels had no impact on the survival of critically ill patients with cirrhosis. In conclusion, this study demonstrates that FGF21 levels are of specific diagnostic value regarding the presence and development of ACLF in patients admitted to ICU for AD of liver cirrhosis. Further studies are warranted to address pathophysiological and possible therapeutic implications. Liver Transplantation 24 595-605 2018 AASLD.

Analysis of the MELD Score Impact in the Outcome of Endovascular Portal Vein Reconstruction.

INTRODUCTION: Endovascular therapy represents a less invasive alternative to open surgery for reconstruction of the portal vein (PV) and the spleno-mesenteric venous confluence to treat Portal hypertension. The objective of this study is to determine if the Model for End-Stage Liver Disease (MELD) score is a useful method to evaluate the risk of morbidity and mortality during endovascular approaches. MATERIAL AND METHODS: Patients that underwent endovascular reconstruction of the PV or spleno-mesenteric confluence were identified retrospectively. Data were collected from November 2011 to August 2016. The MELD score was calculated using international normalized ratio, serum billirubin and creatinine. Patients were grouped into moderate (≤ 15) and high (> 15) MELD. Associations of the MELD score on the postprocedural morbidity, mortality and vessels patency were assessed by two-sided Fisher's exact test. RESULTS: Seventeen patients were identified; MELD score distribution was: ≤ 15 in 10 patients (59%) and > 15 in 7 (41%). Even distribution of severe PV thrombosis was treated in both groups, performing predominately jugular access in the high MELD score group (OR 0.10; 95%; CI 0.014-0.89; p = 0.052) in contrast to a percutaneous transhepatic access in the moderate MELD score group. Analysis comparing moderate and high MELD scores was not able to demonstrate differences in mortality, morbidity or patency rates. CONCLUSION: MELD score did not prove to be a useful method to evaluate risk of morbidity and mortality; however a high score should not contraindicate endovascular approaches. In our experience a high technical success, good patency rates and low complication rates were observed.

Duodenal Recurrence of Fibrolamellar Carcinoma 12 Years After Partial Hepatectomy and Adjuvant Chemotherapy.

Fibrolamellar carcinoma (FLC) has a better prognosis than hepatocellular carcinoma; however, it is a highly recurrent disease. A 17-year-old woman presented with FLC with regional disease at the right lobe of the liver and underwent right hepatic lobe resection plus adjuvant chemotherapy with interferon α and adriamycin. She then presented at age 29 years with anemia. Endoscopy revealed an exofitic lesion in the duodenum, which was a recurrence of FLC. The patient underwent duodenal partial resection of a metastatic FLC tumor with disease-free edges and without neural or lymphoid-vascular involvement, a nonreported site of recurrence.

Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis.

AIM: Evaluate the association between phase angle and the development of hepatic encephalopathy in the long-term follow-up of cirrhotic patients. METHODS: This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. Mann-Whitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy. RESULTS: Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy (18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. Kaplan-Meier curves showed a higher proportion of HE in the group with low phase angle (39%) compared to the normal phase angle group (13%) (P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80 (1.07-3.03)]. CONCLUSION: In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.

Endovascular Reconstruction of Extrahepatic Portal Vein in Noncirrhotic and Nonmalignant Chronic Portal Vein Thrombosis Secondary to an Iatrogenic Stenotic Lesion.

Portal vein (PV) thrombosis (PVT) in the absence of liver disease or thrombophilia is rare. We report a 57-year-old male with a history of stage 3 chronic kidney disease who presented at the emergency department 18 months after abdominal surgery with progressive abdominal pain and distention. Computed tomography revealed PVT with multiple collaterals and moderate ascites. He had undergone partial gastrectomy and gastrojejunal anastomosis at an outside facility for gastrointestinal stromal tumors that caused an iatrogenic stenotic lesion in the PV. The patient underwent balloon angioplasty and endovascular deployment of an 8 mm × 100 mm Viabahn covered stent (W. L. Gore and Associates, Flagstaff, Arizona) in the extrahepatic PV via a transhepatic approach; the device allowed complete restoration of prograde portal flow with clinical improvement. At 6 months from the intervention, he remains symptom-free with normal liver function tests and patent endoprosthesis on antiplatelet therapy.

Embarazo en adolescentes de Jalisco, México: una mirada desde la marginación social / Adolescent pregnancy in Jalisco Mexico: a view from social marginalization

Objetivo: Analizar las condiciones socioculturales, atención prenatal y obstétrica, y del recién nacido, en mujeres adolescentes embarazadas residentes de municipios con muy alta y muy baja marginación, en Jalisco, México durante 2014. Diseño: Estudio cuantitativo, descriptivo transversal. Institución. Secretaría de Salud Jalisco. Participantes: Adolescentes residentes de municipios de muy alta y de muy baja marginación. Metodología: Se revisaron certificados de nacimientos de adolescentes residentes de Jalisco atendidas de parto durante 2014, 140 fueron adolescentes residentes de municipios de muy alta marginación y 21 004 de municipios de muy baja marginación. Principales medidas de resultados: Análisis univariado de condiciones socioculturales, atención prenatal y obstétrica, además de datos del recién nacido. Resultados: Se registraron 28 178 nacimientos; de muy alta marginación (Grupo 1) fueron n=140 (0,5%) y de muy baja marginación (Grupo 2) fueron n=21 004 (74,5%). Del Grupo 1, la media de edad fue 17,1 años, 18,5% tenía 15 años o menos, 41,4% primaria o menos, media del número de embarazos fue 1,35; 20% no recibió atención prenatal, la media del número de consultas era 3,1, el 91% tuvo resolución obstétrica por parto normal, la media del peso de recién nacido fue 3 032,10 gramos. Del Grupo 2 la media de la edad fue 17,5 años, 22,7% era soltera, media del número de embarazos 1,34, media del número de consultas 6,7; el 45,2% tuvo resolución obstétrica por cesárea y la media del peso de recién nacidos fue 3 101,67 gramos. Conclusiones: Existieron diferencias porcentuales y de medias entre los grupos, en características socioculturales (escolaridad, estado civil y seguridad social) y las relacionadas con atención prenatal y obstétrica (control prenatal y resolución del embarazo).

Objective: To analyze the sociocultural conditions, prenatal and obstetrical care, and data of the newborn, in pregnant young women residing in municipalities with very high and very low marginalization in Jalisco, Mexico, in 2014. Design: Quantitative, descriptive cross-sectional study. Institution: Jalisco Health Secretariat. Participants: Adolescents residents of both highly and very low marginalization municipalities. Methodology: Birth certificates of 140 adolescents residing in highly marginalized municipalities (Group 1) and 21 004 residing in municipalities with very low marginalization (Group 2) in Jalisco, Mexico, and who delivered a child during 2014, were reviewed. Main outcome measures: Univariate analysis of social and cultural conditions, prenatal and obstetrical care, data of the newborn. Results: From 28 178 births, 140 (0.5%) adolescents belonged to highly marginalized births (Group 1) and 21 004 (74.5%) occurred in adolescentes of very low marginalization adolescents (Group 2). The average age in Group 1 was 17.1 years, 18.5% were 15 years or less; 41.4% had elementary school or care, the mean number of pregnancies was 1.35; 20% did not receive prenatal care, the mean number of consultations was 3.1, 91% had normal delivery, the average newborn birth weight was 3 032.10 grams. The second group's mean age was 17,5 years , 22.7 % were single, the average number of pregnancies 1.34, the mean number of consultations 6.6 , 45.2% had caesarean section, and the average weight of newborns was 3 101.67 grams. Conclusions: There were differences between groups in sociocultural characteristics (education, marital status and social security) and those related to prenatal and obstetrical care (prenatal and pregnancy resolution).

Elevated circulating levels of IL-21 and IL-22 define a cytokine signature profile in type 2 autoimmune hepatitis patients.

UNLABELLED:  Background and aims. Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver in which the immunological mechanisms involved in tissue destruction and/or repair are still unclear. Different pro-inflammatory cytokines have been shown to play a determinant role in AIH pathogenesis. Here, we aim to compare the circulating levels of pro- and anti-inflammatory cytokines such as IL-6, TNF-?, IL-17A/F, IL-21, IL-22, IL-23, and IL-10 in patients with type 2 AIH compared to patients with type 1 AIH and healthy controls (HC). Fourty-six Mexican patients with AIH were recruited in our study. Patients were classified as type 1 or 2 AIH based on immune serological markers. Fourty-four serum samples from healthy individuals were included as controls. Serum cytokine levels were determined by ELISA technique. RESULTS: Compared to healthy controls, serum levels of IL-17F, IL-21, IL-23, IL-10, IL-6, and TNF-?, but not IL-17A and IL-22, were significantly increased in AIH patients. When patients were grouped by aminotransferase activity, a biomarker of active disease, a positive correlation between serum IL-17F and alanine transaminase (rs: 0.4739; P = 0.0009) and aspartate transaminase (rs: 0.4984; P = 0.0004) levels was found. A cytokine signature profile associated with type 2 AIH was characterized by high serum IL-21 (type 1 AIH: 0.66 pg/mL; type 2 AIH: 331.1 pg/mL; P = 0.0042) and IL-22 (type 1 AIH: 0.1 pg/mL; type 2 AIH: 55.26 pg/mL; P = 0.0028) levels. CONCLUSIONS: We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.