The natural history of cystic fibrosis liver disease a prospective cohort study.

BACKGROUND: Our understanding of the natural history of cystic fibrosis liver disease (CFLD) is limited, leading to uncertainty for patients their families and clinicians when liver abnormalities are identified. AIM: to determine the incidence of CFLD, identify risk factors and document the natural history of liver abnormalities in cystic fibrosis (CF). METHODS: The Irish longitudinal study of CFLD (ILSCFLD) prospectively enrolled 95% of children with CF in 2007. Their liver disease status was classified as (i) advanced liver disease with portal hypertension (CFLD). (ii) nonspecific cystic fibrosis liver disease (NSCFLD) (iii) no liver disease (NoLD) RESULTS: 480/522 (91.9%) children were followed for a median 8.53 years IQR 1.28, of whom 35 (7.29%) had CFLD, 110 (22.9%) NSCFLD and 335 (69.79%) had NoLD. At follow-up 28/445 (6.29%) participants without CFLD at baseline, progressed to CFLD (Incidence 7.51/1000 person years (Pyrs) (95%CI 4.99-10.86). Of these 25/28(89.28%) were <10 years. No participant >10 years of age without clinical or radiological evidence of liver disease at baseline progressed to CFLD. During follow-up 18/35(51.43%) participants with CFLD died or received a transplant, MTx rate 7.75/100 Pyrs (95%CI 4.59-12.25) compared to NSCFLD 2.33/100 Pyrs (95%CI 1.44-3.56) and NoLD 1.13/100 Pyrs (95%CI 0.77-1.59). CFLD was an independent risk factor for mortality in CF. Children with CFLD also had a shorter life expectancy. CONCLUSION: The incidence of CFLD was highest in children under10 years. Children over10 years, with normal hepatic function did not develop CFLD. Research to identify the cause and improve outcome should focus on young children.

Is There an Association between Variceal Bleed and Helicobacter pylori Infection in Cirrhotic Patients with Portal Hypertension?: A prospective cohort study.

Objectives: This study aimed to determine the association between Helicobacter pylori infection and variceal bleeding as well as rebleeding in cases of cirrhosis with portal hypertension. Methods: This prospective cohort study included patients with bleeding oesophageal varices and was conducted at the Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, from August 2016 to July 2018. Results: A total of 190 patients were assessed for eligibility, of which 159 patients were included in this study. Among the 159 patients, 124 (78.0%) had alcohol-related liver disease and eight had hepatitis B virus-related liver disease. Seven patients with varices had bled neither at presentation nor during the follow-up period. A total of 78 (49.1%) patients were H. pylori infected. The primary outcome, which was correlation between prevalence of H. pylori and the incidence of bleeding/rebleeding from varices as well as encephalopathy found that patients with oesophageal varices (adjusted risk [AR] = 0.714) and H. pylori infection (AR = 0.682) had a lower risk of variceal rebleeding. Among H. pylori-negative patients, pepsinogen I was higher in patients with rebleeding (30.7 versus 14.4 ng/mL; P <0.001). The secondary outcome, which was correlation of the site of bleeding with H. pylori infection and the association of the ratio of pepsinogen I/II with bleeding showed that among H. pylori-positive patients, the ratio of pepsinogen I/II was higher in patients with rebleeding (2.9 versus 1.3 ng/mL; P = 0.023). Conclusion: H. pylori infection was associated with a lower risk of rebleeding in cases of cirrhosis with portal hypertension. Irrespective of the status of the H. pylori infection, rebleeding was associated with increased levels of gastric acid output, as demonstrated by the level of pepsinogen.

Ursodeoxycholic acid and liver disease associated with cystic fibrosis: A multicenter cohort study.

BACKGROUND: The efficacy and safety of ursodeoxycholic acid (UDCA) for the treatment of liver disease associated with cystic fibrosis (CF) are under discussion, and clinical practice varies among centers. The study aimed at evaluating if the incidence of severe liver disease differs between CF centers routinely prescribing or not prescribing UDCA. METHODS: We carried out a retrospective multicenter cohort study including 1591 CF patients (1192 patients from UDCA-prescribing centers and 399 from non-prescribing centers) born between 1990 and 2007 and followed from birth up to 31 December 2016. We computed the crude cumulative incidence (CCI) of portal hypertension (PH) at the age of 20 years in the two groups and estimated the subdistribution hazard ratio (HR) through a Fine and Gray model. RESULTS: Over the observation period, 114 patients developed PH: 90 (7.6%) patients followed-up in UDCA prescribing centers and 24 (6.0%) in non-prescribing centers. The CCI of PH at 20 years was 10.1% (95% CI: 7.9-12.3) in UDCA-prescribing and 7.7% (95% CI: 4.6-10.7) in non-prescribing centers. The HR among patients followed in prescribing centers indicated no significant difference in the rate of PH either in the unadjusted model (HR: 1.21, 95% CI: 0.69-2.11) or in the model adjusted for pancreatic insufficiency (HR: 1.28, 95% CI: 0.77-2.12). CONCLUSIONS: CF patients followed-up in UDCA prescribing centers did not show a lower incidence of PH as compared to those followed in centers not prescribing UDCA. These results question the utility of UDCA in reducing the occurrence of severe liver disease in CF.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Prevalence and clinical significance of clinically evident portal hypertension in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND: Clinically evident portal hypertension (CEPH) was previously identified as a prognostic factor for patients with hepatocellular carcinoma (HCC). However, little is known about the prognostic influence of CEPH on the long-term outcome of patients with HCC undergoing transarterial chemoembolization (TACE), particularly in Western populations. OBJECTIVES: This study investigated the prevalence and prognostic influence of CEPH in a Western population of patients with HCC undergoing TACE. METHODS: This retrospective study included 349 treatment-naïve patients that received initial TACE treatment at our tertiary care center between January 2010 and November 2020. CEPH was defined as a combination of ascites, esophageal/gastric varices, splenomegaly and a low platelet count. We assessed the influence of CEPH and its defining factors on median overall survival (OS) in HCC patients. We compared the effects of CEPH to those of well-known prognostic factors. RESULTS: Of the 349 patients included, 304 (87.1%) patients had liver cirrhosis. CEPH was present in 241 (69.1%) patients. The median OS times were 10.6 months for patients with CEPH and 17.1 months for patients without CEPH (log rank p = 0.036). Median OS without a present surrogate was 17.1 months, while patients with one respectively more than two present CEPH surrogates had a median OS of 10.8 and 9.4 months (log rank p = 0.053). In multivariate analysis, CEPH was no significant risk factor for OS (p = 0.190). Of the CEPH-defining factors, only ascites reached significance in a univariate analysis. CONCLUSION: CEPH was present in more than two thirds of the patients with HCC undergoing TACE in our cohort of Western patients. Patients with CEPH had a significantly impaired survival in univariate analysis. However, no significance was reached in multivariate analysis. Thus, when TACE treatment is deemed oncologically reasonable, patients should not be excluded from TACE treatment due to the presence of surrogates of portal hypertension alone.

HISTOPATHOLOGICAL, CLINICAL AND EPIDEMIOLOGICAL FEATURES OF HEPATOPORTAL SCLEROSIS IN A REFERRAL CENTER FOR LIVER DISEASE IN NORTHEASTERN BRAZIL.

BACKGROUND: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE: To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS: We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS: From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION: HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.

Características histopatológicas, clínicas e epidemiológicas da esclerose hepatoportal em um centro de referência para doenças do fígado no Nordeste do Brasil / Histopathological, clinical and epidemiological features of hepatoportal sclerosis in a referral center for liver disease in northeastern brazil

ABSTRACT BACKGROUND: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis. OBJECTIVE: To analyze the profile of patients with HPS in Northeastern Brazil and to demonstrate the pathological characteristics of HPS. METHODS: We retrospectively analyzed cases of OPV in liver biopsies and explants from a referral center for liver in Bahia - Brazil. The qualitative and quantitative analysis of the portal tracts and liver parenchyma was made so that comparisons could be done among the HPS findings of our population and the findings described by other authors. RESULTS: From the 62 patients identified with HPS, 42% were male, while 58% were female. The average age at diagnosis was 48.3 years. From this group, we analyzed the liver biopsy of 10 patients whose diagnosis of schistosomiasis could be ruled out. From these 100% (10/10) presented dense portal fibrosis and portal venous obliteration. Liver parenchymal atrophy was present in 60% (6/10) of the patients, sinusoidal dilation was present in 30% (3/10), the presence of portal septa occurred in 50% (5/10) and dense portal fibrosis in all patients analyzed. Nodular regenerative hyperplasia was found in 30% (3/10) of the patients. CONCLUSION: HPS seems to be neglected and misdiagnosed in Brazil, due to its similarities with schistossomiasis. In our study dense portal fibrosis, obliteration of the portal vein branches, parenchymal atrophy, sinusoidal dilatation and parenchymal nodular hyperplasia were the main histopathological findings and were similar to that described in other countries.

RESUMO CONTEXTO: Esclerose hepatoportal EHP ou venopatia portal obliterativa VPO, um dos diagnósticos diferenciais para a hipertensão portal não cirrótica, é caracterizada pelo desaparecimento dos ramos portais, fibrose portal e septal, fibrose sinusoidal e hiperplasia nodular regenerativa HNR. A EHP é um doença espectral, que pode progredir para hipertensão portal severa. Sua etiopatologia é ainda pouco compreendida, especialmente no Brasil, onde ela é provavelmente subdiagnoticada devido as suas similaridades com a forma hepatoesplênica da esquistossomose. OBJETIVO: Analizar o perfil dos pacientes com EHP no Nordeste do Brasil, e demontrar as características patológicas da EHP. MÉTODOS: Analisamos restrospectivamente os casos de VPO em biópsias hepáticas e explantes de um centro de referência em fígado na Bahia, Brasil. A análise qualiquantitativa dos tratos portais e parênquima hepático foi realizada, permitindo a comparação entre os nossos paciente e os achados descritos por outros autores. RESULTADOS: Entre os 62 paciente identificados com EHP, 42% era do sexo masculino, 58% era do sexo feminino. A média de idade no diagnótico foi 48,3 anos. Desse grupo, analizamos a biópsia hepática de 10 pacientes nos quais o diagnóstico de esquistossomose pode ser excluído. Desses pacientes, 100% 10/10 se apresentou com fibrose portal densa e obliteração venosa portal. Atrofia do perênquima hepático estava presente em 60% 6/10 dos pacientes, dilatação sinusiodal em 30% 3/10 a presença de septos portais ocorreu em 50% 5/10 e fibrose portal densa foi achada em todos os pacientes. Hiperplasia nodular regenerativa foi encontrada em 30% dos pacientes. CONCLUSÃO: A EHP parece ser negligenciada e subdiagnosticada no Brasil, devido as suas similaridades com esquistossomose. Em nosso estudo, fibrose portal densa, obliteração dos ramos da veia porta, atrofia do parênquima, dilatação sinusoidal e hiperplasia nodular do parênquima foram os principais achados histopatológicos e foram semelhantes aos descritos em outros países.

Increased Prevalence of Left Lobe Atrophy in Long-standing Extrahepatic Portal Vein Obstruction.

OBJECTIVES: The aim of this study was to describe long-term changes in standard blood tests and ultrasound (US) findings in pediatric patients with Extrahepatic Portal Vein Obstruction (EHPVO) who have not undergone Meso-Rex Bypass (MRB) surgery. METHODS: US, laboratory, and endoscopic data of 77 patients were analyzed and compared at 2 different points in time: at initial workup and at most recent follow-up. Differences were assessed using McNemar and Wilcoxon tests, while correlations were evaluated using generalized estimating equations. RESULTS: Upper gastrointestinal bleeding was the most frequent initial manifestation of EHPVO, in 45.4% of subjects. The mean age at diagnosis was 4.3 years. Seventy-four percentage had a previous history of umbilical catheterization and/or neonatal sepsis. Over time, there was a significant increase in the prevalence of leukopenia, thrombocytopenia, and, interestingly, of left lobe atrophy (LLA), even though the number of esophageal varices and the need for endoscopic interventions reduced. A significant correlation was found between history of umbilical catheterization and LLA, splenomegaly and LLA, and gallbladder wall thickening and LLA. Overall, the number of patients with cholelithiasis at initial workup was low (and therefore, not analyzed with inferential statistics); however, we observed a relative increase over time. CONCLUSIONS: In this cohort of patients with EHPVO followed over more than 8 years without treatment with MRB, we report the novel finding of a significant increase in the prevalence of LLA over time. LLA correlated with past medical history of umbilical catheterization, and findings of splenomegaly and gallbladder wall thickening. We propose that that LLA should be further explored as a marker of portal hypertension, particularly in the context of a history of umbilical catheterization.

Reconstructing spleno-mesenterico-portal cofluence by bifurcated allogeneic vein in local advanced pancreatic cancer-a feasible method to avoid left-sided portal hypertension.

BACKGROUND: Left-sided portal hypertension is usually found in patients undergoing pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) confluence resection. This study is to explore the outcomes of S-M-P confluence reconstruction after resection by using bifurcated allogeneic vein. METHODS: Clinicopathologic data of patients who underwent extensive PD with S-M-P confluence resection for carcinoma of pancreatic head/uncinate process in our hospital between December 2011 and August 2018 were retrospectively reviewed and clinical outcomes of vein reconstruction after resection were analyzed. RESULTS: Of the 37 patients enrolled, S-M-P reconstruction by bifurcated allogeneic vein was performed in 24 cases (group 1) and simply splenic vein ligation in 13 cases (group 2). Items including pathological results, blood loss, and complications were comparable between the two groups, operation time was longer in group 1 (573.8 vs. 479.2 min, p = 0.018). Significantly decreased platelet count (205.9 vs. 133.1 × 109 /L, p = 0.001) and increased splenic volume (270.9 vs. 452.2 ml, p < 0.001) were observed in group 2 at 6 months after operation. The mean splenic hypertrophy ratio was 1.06 in group 1 and 1.63 in group 2, respectively (p < 0.001). There were four patients with varices were found in group 2, none in group 1. CONCLUSIONS: Without increased complications, reconstructing S-M-P confluence by bifurcated allogeneic vein after resection may help to avoid left-sided portal hypertension.

Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses .

BACKGROUND AND AIMS: Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. METHODS: Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. RESULTS: Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. CONSLUSIONS: Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

Prevalence and Associated Factors of Portopulmonary Hypertension in Patients with Portal Hypertension: A Case-Control Study.

BACKGROUND AND AIMS: There are few studies on the prevalence and clinical characteristics of portopulmonary hypertension (POPH) in patients with portal hypertension. In addition, invasive right heart catheterization further limits the clinical diagnosis of POPH patients. METHODS: From January 2018 to December 2019, 1004 patients with portal hypertension were treated in the Department of Hepatology, the First Hospital of Jilin University. Based on the inclusion and exclusion criteria, 188 patients with portal hypertension were finally included. We collected complete clinical data, laboratory examinations, and imaging examinations. Patients were divided into a POPH group and a non-POPH group based on echocardiographic results. We calculated the prevalence of POPH in patients with portal hypertension. The differences in clinical characteristics of the two groups of patients were compared. RESULTS: The prevalence of POPH in patients with portal hypertension was 2.8%. Among the 188 patients with portal hypertension with fingertip oxygen saturation < 95% at rest, 28 patients had POPH (12 males and 16 females), with an average age of 63 ± 8, and 160 patients did not have POPH (110 males, 50 women), with an average age of 59 ± 11. The proportion of women in the POPH group (P < 0.01) and patients without liver cancer (P = 0.044) was high. Compared to patients without POPH, patients with POPH had lower hemoglobin (related to the severity of anemia, P < 0.01), higher creatinine (P < 0.05), and lower partial pressure of oxygen and carbon dioxide (P < 0.05). Patients with POPH had a higher incidence of atrial enlargement, ventricular enlargement, mitral valve regurgitation, tricuspid regurgitation, pulmonary artery widening, pericardial effusion, and aortic regurgitation than those without POPH. The risk of POPH did not increase with the aggravation of the Child-Pugh classification. CONCLUSION: The prevalence of POPH in patients with portal hypertension is 2.8%. The proportion of women and nonliver cancer in POPH patients was higher than that in non-POPH patients. In addition, the POPH group had higher creatinine and lower hemoglobin, and echocardiography showed that POPH patients had more cardiac structural changes. In patients with portal hypertension, the risk in patients with POPH has nothing to do with the Child-Pugh classification and MELD score.

Left-sided Portal Hypertension After Pancreaticoduodenectomy With Resection of the Portal Vein/Superior Mesenteric Vein Confluence in Patients With Pancreatic Cancer: A Project Study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

OBJECTIVE: The aim of this study was to evaluate how often left-sided portal hypertension (LPH) develops and how LPH affects the long-term outcomes of patients with pancreatic cancer treated with pancreaticoduodenectomy (PD) and resection of the portal vein (PV)/superior mesenteric vein (SMV) confluence. SUMMARY BACKGROUND DATA: Little is known about LPH after PD with resection of the PV/SMV confluence. METHODS: Overall, 536 patients who underwent PD with PV/SMV resection were enrolled. Among them, we mainly compared the SVp group [n=285; the splenic vein (SV) was preserved] and the SVr group (n = 227; the SV was divided and not reconstructed). RESULTS: The incidence of variceal formation in the SVr group increased until 3 years after PD compared with that in the SVp group (38.7% vs 8.3%, P < 0.001). Variceal bleeding occurred in the SVr group (n = 9: 4.0%) but not in the SVp group (P < 0.001). In the multivariate analysis, the risk factors for variceal formation were liver disease, N factor, conventional PD, middle colic artery resection, and SV division. The only risk factor for variceal bleeding was SV division. The platelet count ratio at 6 months after PD was significantly lower in the SVr group than in the SVp group (0.97 vs 0.82, P < 0.001), and the spleen-volume ratios at 6 and 12 months were significantly higher in the SVr group than in the SVp group (1.38 vs 1.00 and 1.54 vs 1.09; P < 0.001 and P < 0.001, respectively). CONCLUSIONS: PD with SV division causes variceal formation, bleeding, and thrombocytopenia.

Vitamin A levels reflect disease severity and portal hypertension in patients with cirrhosis.

BACKGROUND AND AIMS: The liver plays a key role in the storage, metabolism and homeostasis of fat-soluble vitamins. We investigated the relation of Vitamin(Vit)A/D/E serum levels with severity of liver disease and portal hypertension (PHT). METHODS: VitA/D/E serum levels were assessed in 234 patients with advanced chronic liver disease (ACLD, i.e. hepatic venous pressure gradient [HVPG] ≥ 6 mmHg). Patients with hepatocellular carcinoma, pre-/post-hepatic PHT, TIPS or liver transplantation were excluded. RESULTS: Most patients were male (n = 153; 65%) with a median age of 57.6 (49.7-64.5) years. Thirty-two (14%) patients had HVPG 6-9 mmHg, 66 (28%) 10-15 mmHg, and 136 (58%) ≥ 16 mmHg, respectively. VitD deficiency (25-OH-vitamin-D <50 nmol/L) was found in 133 (57%) with higher prevalence in Child-Turcotte-Pugh (CTP)-C: 85% vs. B: 66% vs. A: 47% (p < 0.001). VitD levels displayed significant but weak correlations with hepatic dysfunction and PHT. VitE levels were normal in 227 (97%) patients and displayed no relevant association with hepatic dysfunction or PHT. Only 63 (27%) patients had normal (>1.05 µmol/L) VitA levels, while 58 (25%) had mild (0.70-1.04 µmol/L), 71 (30%) moderate (0.35-0.69 µmol/L), and 42(18%) severe(<0.35 µmol/L) VitA deficiency. VitA correlated with HVPG (Rho = -0.409), CTP score (Rho = -0.646), and serum bile acid levels (Rho = -0.531; all p < 0.001). The prevalence of decompensated ACLD (dACLD) continuously increased with severity of VitA deficiency (no: 40% vs. mild: 51% vs. moderate: 67% vs. severe: 91% had dACLD; p < 0.001). CTP score (per point; OR 2.46; 95%CI 1.80-3.37; p <0.001), age (per year; OR 0.95; 95%CI 0.92-0.98; p = 0.001) and elevated bile acid levels(>10 µmol/L; OR 3.62; 95%CI 1.61-8.14; p = 0.002) were independently associated with VitA deficiency. CONCLUSION: VitA and VitD but not VitE deficiencies are highly prevalent in ACLD. VitA deficiency strongly correlates with hepatic dysfunction, PHT and bile acid levels and is associated with decompensated ACLD. TRIAL REGISTRATION NUMBER: NCT03267615.

High platelet count as a poor prognostic factor for liver cancer patients without cirrhosis.

A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Patients undergoing initial and curative resection for HCC were included. Surgical outcomes were compared between the high platelet (platelet count ≥ 20 × 104/µL) and control (< 20 × 104/µL) groups in patients without cirrhosis and between the low platelet (< 10 × 104/µL) and control (≥ 10 × 104/µL) groups in patients with cirrhosis. Among patients without cirrhosis, tumor was larger (P < 0.001) and tumor thrombus was more frequent (P < 0.001) in the high-platelet group than in the control group. After a median follow-up period of 3.1 years (range 0.2-16.2), median overall survival was 6.3 years (95% confidence interval [CI], 5.3-7.8) and 7.6 years (6.6-10.9) in the high-platelet (n = 273) and control (n = 562) groups, respectively (P = 0.027). Among patients with cirrhosis, liver function was worse (P < 0.001) and varices were more frequent (P < 0.001) in the low-platelet group. The median overall survival of patients in the low-platelet group (n = 172) was significantly shorter than that of patients in the control group (n = 275) (4.5 years [95% CI, 3.7-6.0] vs. 5.9 years [4.5-7.5], P = 0.038). Taken together, thrombocytopenia indicates poor prognosis in HCC patients with cirrhosis, while thrombocytosis is a poor prognostic predictor for those without cirrhosis.

Left-sided portal hypertension after pancreatoduodenectomy with resection of the portal/superior mesenteric vein confluence. Results of a systematic review.

BACKGROUND: Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension. Left-sided portal hypertension presents with splenomegaly and varices and may cause severe gastrointestinal bleeding. The aim of the study is to review the incidence, treatment, and preventive strategies of left-sided portal hypertension. METHODS: A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify all studies published up to September 30, 2019 reporting data on patients with left-sided portal hypertension after pancreatoduodenectomy with venous resection. RESULTS: Eight articles including 829 patients were retrieved. Left-sided portal hypertension occurred in 7.7% of patients who had splenic vein preservation and 29.4% of those having splenic vein ligation. Fourteen cases of gastrointestinal bleeding owing to left-sided portal hypertension were reported at a mean interval of 28 months from pancreatoduodenectomy. Related mortality at 1 month was 7.1%. Treatment of left-sided portal hypertension consisted of splenectomy in 3 cases (21%) and colectomy in 1 (7%) case, whereas radiologic, endoscopic procedures or conservative treatments were effective in the other cases (71%). CONCLUSION: Left-sided portal hypertension represents a potentially severe complication of pancreatoduodenectomy with venous resection occurring at greater incidence when the splenic vein is ligated and not reimplanted. Left-sided portal hypertension-related gastrointestinal bleeding although rare can be managed depending on the situation by endoscopic, radiologic procedures or operative intervention with low related mortality.

Risk factors for sinistral portal hypertension and related variceal bleeding in patients with chronic pancreatitis.

OBJECTIVES: Sinistral portal hypertension (SPH) is an uncommon complication of chronic pancreatitis (CP) and can result in severe gastrointestinal bleeding. The aim of this study was to determine the prevalence and the potential risk factors for SPH and related gastrointestinal variceal bleeding in patients with CP. METHODS: We retrospectively reviewed all patients with SPH due to CP admitted to our hospital from July 2014 to June 2019 in this case-control study. Patients with CP without SPH were randomly selected as controls during the study period (case: control  =  1:2). The characteristics, medical history, course of CP, characteristics associated with SPH, and follow-up evaluations of the patients were documented in detail. The prevalence rate of SPH in patients with CP and related gastrointestinal bleeding was calculated. Risk factors for SPH and related variceal bleeding were analyzed using univariate or multivariate logistic regression analysis. RESULTS: The prevalence of SPH was 2.7% (89/3358) in patients with CP. Independent risk factors for SPH included alcohol consumption (P = 0.030), history of acute pancreatitis (P = 0.010), diabetes mellitus (P < 0.001), and pseudocysts (P < 0.001). Overall 17 (19.1%) patients suffered from related gastrointestinal bleeding. Between the bleeding and non-bleeding groups, there were significant differences in the types of CP, existence of stones, gastric varices diagnosed before bleeding, splenomegaly and hypersplenism by univariate analysis. CONCLUSION: SPH is a rare complication of CP that is associated with a relatively low risk of variceal bleeding.

Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals.

BACKGROUND & AIMS: It is important to know which patients with hepatitis C are likely to develop liver-related complications after achieving a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy. We aimed to describe the incidence of liver-related events in a population of patients with HCV-associated compensated advanced chronic liver disease (cACLD) who achieved SVR and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: This 2-center prospective study included 572 patients with cACLD who had been treated with DAAs and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child-Pugh class A). Laboratory work-up and LSM were performed at baseline and at 1 year of follow-up. RESULTS: The median follow-up was 2.8 years during which 32 patients (5.6%) presented with a liver-related event. The incidence rate (IR) of portal hypertension-related decompensation was 0.34/100 patient-years. These patients all had baseline LSM >20 kPa, and LSM did not improve during follow-up in 4 out of 5 of them. Hepatocellular carcinoma (HCC) occurred in 25 patients (IR 1.5/100 patient-years). Albumin levels at follow-up (hazard ratio [HR] 0.08; 95% CI 0.02-0.25) and LSM <10 kPa at follow-up (HR 0.33; 95% CI 0.11-0.96) were independently associated with the risk of HCC. Combining both predictors identified 2 groups with differing risk of HCC occurrence: those with LSM ≥20 kPa at follow-up or those with LSM between 10-20 kPa and albumin levels <4.4 g/dl were at the highest risk (IR ≥1.9/100 patient-years). Visual nomograms predicting HCC risk based on LSM and albumin at 1 year of follow-up were constructed. CONCLUSION: In patients with HCV-related cACLD who have achieved SVR with DAAs, HCC is the most frequent liver-related event. Both albumin levels and LSM are useful for stratifying patients based on their risk of developing HCC during follow-up. LAY SUMMARY: New oral antivirals can cure chronic hepatitis C infection, however patients with advanced chronic liver disease are still at risk of presenting with liver-related complications. The most frequent complication after oral antiviral therapy in asymptomatic patients with advanced chronic liver disease was liver cancer. The use of simple parameters such liver stiffness and albumin levels after treatment can help to identify patients at higher or lower risk of liver cancer.

Prevalence, nature, and predictors of colonic changes in children with extrahepatic portal vein obstruction.

BACKGROUND AND AIMS: The medical literature on colonic changes in children with extrahepatic portal venous obstruction (EHPVO) is limited. We evaluated EHPVO children for prevalence, nature, and relation of colonic changes with disease duration, extent of splenoportal axis (SPA) thrombosis, portal hypertensive gastropathy (PHG), and esophageal varices (EVs). The correlation between histologic and endoscopic changes was studied. METHODS: Subjects were evaluated by colonoscopy with ileoscopy and biopsy sampling, clinico-laboratory profiles, and SPA imaging. Colonic changes were classified as varices (rectal/colonic) and portal hypertensive colopathy (PHC; colitis-like or vascular lesions). Morphometric analysis of colonic biopsy specimens was performed. RESULTS: Fifty-four children (median age, 12 years [range, 8-15]; hematochezia in 9 [16.6%]) were evaluated. Rectal and colonic varices were seen in 51 (94%) and 2 (3.7%) cases, respectively. Seventy-five percent of patients had PHC, and colitis-like lesions were more common than vascular lesions (36/40 vs 23/40; P = .001). Colopathy changes were pancolonic in 52.5%, left-sided in 42.5%, and right-sided in 5% of cases. Sixteen percent of patients (8/49) had ileal changes. Children with PHC had PHG more often (90% vs 57%; P = .01), more endotherapy sessions (mean 6 [range, 4-8] vs 2 [range, 1-4]; P = .03), and large EVs less often (12.5% vs 43%; P = .02) than those without colopathy. The extent of SPA thrombosis was similar in patients with and without PHC. The number of capillaries per crypt was higher in EHPVO than in control subjects. Morphometric changes had no correlation with endoscopy. CONCLUSIONS: Most EHPVO children had colonic changes, and 16% had ileopathy. "Colitis-like" changes and left-side involvement were more common. Patients with PHG and eradicated EVs had a higher risk of PHC.

Occurrence, outcomes and predictors of portal hypertension in cystic fibrosis: A longitudinal prospective birth cohort study.

BACKGROUND: The reported prevalence of portal hypertension (PH) in Cystic Fibrosis is variable, incidence rates rarely provided and the utility of liver function tests (LFT's) early in life to predict PH is questionable. The aims were to (1) determine PH prevalence (P) and incidence rate (IR) and combined mortality transplant (MTX) data in PH vs non-PH patients and (2) to assess association of LFTs in early life with liver disease and PH. METHOD: (1) A double centre longitudinal cohort study of 577 CF patients diagnosed by newborn screening (NBS) with annual examinations for PH up to 18.5 years of age (max) was performed over 28 years for P, IR, and MTX data; (2) Cox proportional hazard models were used to assess the association of elevated LFTs on 2 or more occasions over 0-6.5 years and PH. RESULTS: 51/577(8.8%) developed PH with an average IR of near 3/1000 patient years per 5 year interval representing young, mid and late childhood respectively in patients 3-18 years of age. Combined mortality/liver transplant occurred in 12/51 (23.5%) PH and 25/526 (4.8%) non-PH (p < 0.001). Elevated enzymes particularly GGT (HR:5.71, 95% CI 3.11-10.47); ALT/GGT (HR: 5.56, 95% CI 2.82-10.98); and ALP/GGT (HR: 5.74, 95% CI 2.78-11.86) were associated with the onset of PH. CONCLUSION: This birth cohort with annual examination for PH provides an accurate assessment of the prevalence, and IR of PH and MTX of PH vs non-PH. Early elevated LFTs are associated with onset of MBC/PH.