Absence Of Esophageal Varices Research Articles

Etiologies of Splenic Venous Hypertension: A Review.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Non-invasive Fibrosis Markers for Predicting Esophageal Varices: A Potential Alternative to Endoscopic Screening.

Chronic liver infections and diseases lead to chronic liver injury, which results in fibrosis. Due to this continuous scarring and regeneration, cirrhosis occurs, which is also responsible for several adverse sequelae, including but not limited to esophageal varices. Cirrhosis has resulted in patients' increased morbidity and mortality, especially in low socioeconomic settings such as Pakistan. Endoscopy is the gold standard for measuring the presence or absence of esophageal varices, along with their grade. Currently, some non-invasive markers (aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), fibrosis 4 (FIB-4), AAR to platelet ratio index (AARPRI), aspartate aminotransferase-to-platelet ratio index (APRI), S-index, King's score) are being established that make use of laboratory tests, such as a complete blood profile, liver function profile, and coagulation profile, to estimate the extent of hepatic fibrosis. The objective of this study is to establish a correlation between non-invasive markers of fibrosis and the presence of esophageal varices and to assess their potential as a substitute for gastrointestinal endoscopy screening. Additionally, the study aims to compare these six scores, thereby generating data on their individual and relative accuracy. This was a cross-sectional study conducted at the Shalamar Institute of Health Sciences, Lahore, Pakistan. Outpatient (OPD) data were obtained from the Shalamar online portal system from June 2022 to December 2022. Laboratory tests, abdominal ultrasounds, and endoscopy results were accessed and recorded in the questionnaire. The patient's medical records and contact numbers were also noted in case further questions arose. Data were then compiled into a Microsoft Excel spreadsheet (Microsoft Corp., Redmond, WA) and analyzed after computing the non-invasive procedure formulas. It was analyzed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY). P-values were calculated, and conclusions were drawn. Of the sample size of 100 patients with liver damage and injury, 60% were male and 40% were female. Among males, 15% had a milder (grade 1)degree of esophageal varices, and 45% had a moderate to advanced degree (grades 2-3) of esophageal varices. Among females, 19% had mild (grade 1) varices, while 21% had severe (grade 3) varices. The most common cause of varices in patients who had developed fibrosis and/or cirrhosis was hepatitis C, with a wide margin of other causes. The p-values obtained showed that from the selected list of non-invasive markers of fibrosis, only FIB-4 and AARPRI were statistically significant with p-values of 0.036 and 0.022, respectively. Though endoscopy is currently the gold-standard procedure for detecting the presence or absence and grade of esophageal varices, it is invasive, which makes the patients extremely uncomfortable and apprehensive. It can also lead to post-procedure infection, internal hemorrhages, and trauma due to instrument use. Due to its invasive nature, some patients also tend to refuse this procedure. Non-invasive fibrosis markers can help make a diagnosis without undergoing an endoscopy, which in turn will improve patient compliance and satisfaction. It was observed that FIB-4 and AARPRI can be used together as reliable markers to assess the presence or absence of esophageal varices.

Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease

We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47-3.41) and large (HR 3.86, 95% CI 2.34-6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39-5.05) and large (HR 4.90, 95% CI 2.49-9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16-6.74) or large (HR 5.29, 95% CI 1.96-14.2) OV was also independently associated with incident PVT. In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Prediction of Esophageal Varices by Non-Invasive Markers in Patients of Hepatic Cirrhosis due To Chronic Hepatitis C

Background: Esophageal varices develop as a consequence of portal hypertension in patients with chronic liver disease. Predicting the varices by non-invasive methods at the time of registration is likely to predict the need for prophylactic β blockers or endoscopic variceal ligation in patients with cirrhosis and portal hypertension. Objective: To evaluate the accuracy of combined non-invasive parameters in predicting the presence of esophageal varices in patients with hepatic cirrhosis due to chronic hepatitis C, using the positive predictive value (PPV) as a measure of performance. Methods: In this cross-sectional study conducted in the Department of Medicine, Unit-I, Sir Ganga Ram Hospital, Lahore, 125 patients fulfilling the inclusion criteria were included. Platelet count, Prothrombin Time/International Normalized Ratio (PT/INR) and portal vein diameter was assessed. Upper gastrointestinal endoscopy was done in all patients to check the presence or absence of esophageal varices. Results: Mean age of the patients was 52.52±8.39 years with 64% males. Mean PT was 10.09±3.13, mean INR was 1.75±0.22, mean platelet count was 83.56±13.47 while mean portal vein diameter was 13.79±0.84. In 61 patients (48.8%) esophageal varices were present on endoscopy and in 85 patients (68%) esophageal varices were predicted by combined non-invasive parameters. Positive predictive value of combined non-invasive parameters was 71.7%. Practical implications: Noninvasive predictors can be used as a screening tool to decide need for preventive drug therapy in esophageal varices and thus help reduce the workload and financial burden of routine endoscopies in all cirrhosis patients. Conclusion: The results suggest that combined non-invasive parameters may be a useful tool in the prediction of esophageal varices in patients with hepatic cirrhosis Keywords: Esophageal varices, Non-invasive predictors, Portal hypertension

Elevation of AST/ALT Ratio in Association with Severity of Esophageal Varices in Patients with Hepatic Cirrhosis

Objective: To determine the elevation of AST/ALT ratio in association with severity of esophageal varices in patients with hepatic cirrhosis. Study Design: Cross sectional survey Place and Duration of Study: Medical Unit II, Jinnah Hospital Lahore from November 2018 to April 2019 Methodology: One hundred and ten subjects were enrolled. The complete history, physical examination and appropriate investigations were done like liver functions test to see the ratio of AST/ALT and upper GI Endoscopy to confirm the presence or absence of esophageal varices. Results: The mean age of the patients was 45.6±5.2 years with 77.27% males and 22.73% females. Paquet grading system showed that esophageal varices were presented in 20.9% grade II. Within the 65 cases of esophageal varices 30 patients of liver cirrhosis were having a 27% high risk of esophageal varices. ALT and AST were significantly higher in high risk esophageal varices. Conclusion: The elevated level of ALT and AST are significantly associated with the severity of esophageal varices in hepatic cirrhosispatients. Key words: Elevation, AST/ALT ratio, Association, Esophageal varices, Hepatic cirrhosis

PLATELET COUNT AND SPLEEN DIAMETER RATIO FOR NON INVASIVE DIAGNOSIS OF ESOPHAGEAL VARICES

BACKGROUND: Portal Hypertension and its consequences mainly, Esophageal Varies (EVs) is one of the most important causes of morbidity and mortality in patients with cirrhosis of liver. Upper GI endoscopy is the investigation of choice for diagnosis of EVs and periodic endoscopies have been recommended for monitoring of varices. There is a need for non-invasive parameters to detect the presence of EVs. Identication of noninvasive predictors of EVs will help us to carry out EGD in selected groups of patients. Unnecessary endoscopies can be avoided and at the same time, patients who require endoscopy can be referred to a higher center, where facilities for endoscopy are available. Among the non-invasive modalities, the platelet count and bipolar spleen diameter ratio has shown promising results in terms of its accuracy in predicting the presence of Esophageal Varices in many studies MATERIALS AND METHODS: Patients with chronic liver disease diagnosed using clinical, Laboratory and ultrasound parameters were assessed using esophagogastroduodenoscopy for the presence or absence of esophageal varices. USG abdomen was done to assess for bipolar splenic diameter and the presence or absence of EV's was correlated with the platelet count/ splenic diameter ratio, CHILD SCORE, MELD score, Platelet count alone and splenic diameter alone. Platelet count/SD ratio of 909 based on previous studies was correlated with the presence or absence of varices. Statistical analysis was done using IBM SPSS software version 20.0 and variables showing statistically signicant correlations with presence of arices were used for plotting ROC curves to assess the cut of points which could be used for non invasive prediction of varices. RESULTS: The PC/SD ratio cut off (909), based on previous studies for non invasive diagnosis of Esophageal Varices gave sensitivity and specicity of 97.9% and 91.7% respectively, in our study, which was statistically signicant (P value <0.001). The positive predicitive value and negative predictive value of the PC/SD ratio (909) was 96.5% and 94.8% respectively and the accuracy of the test was 96%. ROC curve for Platelet count and Splenic diameter ratio area under the curve is 97.8% with P value < 0.001 and cutoff value 895.02 with sensitivity 96.6% and specicity 96.5%. The Positive predictive value and negative predictive value of PC/SD ratio of 895 was found to be 98.6% and 91.8% respectively and the accuracy of the test 96.5%. ROC curve for Child score in our study, area under the curve 71% with a signicant P value < 0.001, and cut-off value obtained for Child score was 8.50 with sensitivity 64.8% and specicity 63.8 %. ROC curve for MELD score revealed area under the curve was 74.3% with P value as < 0.001, and the cut-off value was 15.5 with sensitivity 67.6 % and specicity 67.2%. ROC curve for Platelet count in our study, the area under the curve was 94.5% with P value as < 0.001, and the cut-off value was 108500 with sensitivity and specicity of 89.7% and 89.4% respectively. The ROC curve for Spleen diameter in our study revealed that the area under the curve was 86.8%% with P value as < 0.001, and the cutoff value was 121 with sensitivity and specicity of 78.9% and 81.0% respectively. CONCLUSION: Among the variables studied for non-invasive diagnosis of Esophageal varices, the Platelet count / Spleen diameter ratio had the best sensitivity and specicity for diagnosing EVs. In view of low sensitivities and specicities for the cut off values obtained for Child score, MELD score, platelet count and spleen diameter, these indices may not be useful as PC/SD ratio in the non-invasive prediction of EV's. The Platelet count / Splenic diameter ratio may be proposed as a safe parameter for diagnosing Esophageal Varices in Chronic Liver disease noninvasively, where resources are limited and endoscopy facilities are not available, to select the patients with probable Esophageal Varices who can be referred to higher centres

Peripheral Blood Monocytes in Prediction of Response to Direct Acting Antiviral Drugs in Chronic HCV Patients

Background: Eradication rate of hepatitis C virus (HCV) infection had dramatically increased in era of direct acting antivirals (DAAs). However, predicting relapse post-treatment had to be more speculated. Aim: to evaluate role of peripheral blood monocytes (PBMCs) HCV PCR as predictor of post-treatment relapse. Methods: For chronic HCV patients who achieved end of treatment response, HCV PCR at PBMNs was assessed in relation to SVR. Results: 112 out of 118 cases had SVR 24 with only six relapsers (5.1%). Negativity of triple HCV RNA was significantly lower in relapsers than in patients who achieved SVR (16.7% versus 92.9%, p= 0.001). Cases with two positive strands were relapsers (n= 2,33.3%). Single RNA positive strand was detected in 50% of relapsers (n=3) and in 8 out of 112 (7.1%) of patients who achieved SVR. Significant factors affecting treatment response were absence of esophageal varices, negativity of triple HCV RNA, albumin, platelets, INR, creatinine and MELD score. On multivariate analysis, negativity of triple HCV RNA was significant predictor of achieving SVR with 208.38 Odds Ratio and 95% CI (4.93-8809.97, p= 0.005). Conclusion: Relying on presence of HCV on PBMCs at end of treatment with DAAs might be a trustworthy independent predictor of relapse.

Platelet Count/Splenic Diameter Ratio to Predict Oesophageal Varices in Portal Hypertension

Background: One of the major causes of morbidity and mortality in Nepal is portal hypertension due to liver cirrhosis. In rural areas where a lot of cases of cirrhosis of liver are prevalent and endoscopic expertise and facilities are not available, predicting the presence of esophageal varices through non-invasive means may reduce a large number of unnecessary endoscopies. This study is to identify the relationship of platelet count /splenic bipolar diameter ratio with the presence of esophageal varices in portal hypertension.
 Materials and methods: Eighty patients were included in this study between Jestha 2072 to Baisakh 2073 with the diagnosis of portal hypertension admitted in Bir hospital, Kathmandu which is a tertiary hospital of government of Nepal, which were mostly due to liver cirrhosis. The patients fulfilling the inclusion criteria underwent lab investigations, ultra sonogram and UGI endoscopy. The data were assessed for descriptive studies and means were compared using t-test. The cut off value of platelet count to spleen diameter ratio of 1150 was used to predict the presence or absence of oesophageal varices. Statistical analysis was done using SPSS 20 software
 Results: Platelet count to splenic diameter ratio with a cut off value of 1150 has sensitivity of 89.7%, specificity of 83.3%, positive predictive value of 96.8% and negative predictive value of 58.8% (p= 0.002, CI=95%) with 89.5 % accuracy.
 Conclusion: Platelet count to splenic bipolar diameter ratio can be a good predictor of presence of esophageal varices in patients with portal hypertension in the resource poor settings.

Clinical Value of Serum Fibrosis Biomarkers in Prediction of Esophageal Varices in Cirrhotic Patients

AbstractBackground: Esophageal varices is one of the major com-plications of portal hypertension, occur in approximately 30%-70% of cirrhotic patients. As portal hypertension is a consequence of liver fibrosis, serum fibrosis biomarkers could serve as non invasive predictors for esophageal varices and their grades.Aim of Study: Determine the frequency and grading of esophageal varices in a group of cirrhotic patients with no history of upper gastrointestinal bleeding, and also evaluate and compare the predictive value of APRI, AAR, FIB-4, FI, and king scores in predicting the presence of varices and their grade.Patients and Methods: One hundred and one cirrhotic patients were included in the study. The diagnosis of liver cirrhosis was based on clinical, laboratory and ultrasonographic data. An upper GIT endoscopic examination was performed for all patients for the diagnosis of presence or absence of esophageal varices. Serum fibrosis biomarkers were calculated from data available on the first day hospital admission and used as prognostic indicators for presence and grade of esophageal varices.Results: Patients with esophageal varices had significantly lower mean values of platelet counts and albumin levels than those without esophageal varices (p=0.015, p=0.045; respec-tively). Also there was a significant difference between patients with and without esophageal varices as regard FI score (p= 0.016). Patients with medium to large esophageal varices had significantly lower mean values of platelet counts than those with no to mild esophageal varices. Also there was a significant difference between patients with medium to large esophageal varices and those with no to mild esophageal varices as regard FI, FI B-4 and King scores (p=0.003, p=0.001, p=0.017; respectively). The FI score was accurate in predicting presence of esophageal varices in cirrhotic patients. Using 3.52 cut-off value, a prediction of presence or absence of EV could be made in 62.4% of cirrhotic patients. FIB-4 (cut off value 3.64), FI (cut off value 3.65) and King (cut off value 26.65) scores may perform better in prediction of high grade esopha-geal varices than in prediction of presence of esophageal varices.Conclusion: Fibrosis index prediction score at cut off value 3.52 is a moderately sensitive noninvasive tool that can predict the presence of esophageal varices in cirrhotic patients with acceptable accuracy. Thus can reduce the burden and make screening for esophageal varices less stressful for the patients. The combination of FI score (cut off value 3.64), FIB-4 score (cut off value 3.65) and King's score (cut off value 26.65) could be used as an initial screening tests to detect patients with high risk EV for whom endoscopy may be more beneficial. Hence the benefit of doing upper endoscopy overweight the burden of this maneuver.

Acoustic radiation force impulse sonography‐based noninvasive prediction of cirrhosis and esophageal varices

Esophagogastroduodenoscopy (EGD) screening is currently suggested with a practice guideline for all cirrhosis patients, but the true EGD screening rate is low. Our study evaluates noninvasive variables—including liver stiffness (LS), spleen stiffness (SS), and spleen diameter—based on acoustic radiation force impulse (ARFI) sonography for noninvasive prediction of cirrhosis and esophageal varices (EVs). In our study, 118 patients (mean age 57.11 ± 11.23), who were classified into a cirrhosis group and a chronic liver disease group, were compared statistically on their blood data and ARFI sonography. To identify the most effective variable for noninvasive prediction of EVs, the cirrhosis group was further divided into two subgroups by the presence or absence of EVs. EV and non‐EV (NEV) patients were compared statistically using blood data, spleen diameter, LS, and SS. The LS cutoff value for predicting cirrhosis was determined as 1.64 m/s, which carried a sensitivity of 81.2% and a specificity of 93.9%. SS and spleen diameter met a significant difference for EV prediction. Spleen diameter with a cutoff value of 10.69 cm carried a sensitivity of 96.2% and a specificity of 56.3%; SS with a cutoff value of 2.82 m/s carried a sensitivity of 96.2% and a specificity of 50%. In our study, a new cutoff criterion composed of spleen diameter and SS was suggested as a better clinical tool for the screening of EVs.

Association between Liver Stiffness and Gastro-Esophageal Varices in Chronic Liver Diseases

Objective: Elastography is a non-invasive examination method that can estimate the extent of liver fibrosis, measured as liver stiffness (LS). We examined the relationship between gastro-esophageal varices and the LS and how to predict esophageal varices and varices bleeding by LS. Methods: From 2014 to 2016, we conducted a retrospective study of 138 subjects, all of whom were patients with chronic liver disease, including NAFLD, alcoholic liver disease, primary biliary cholangitis, viral hepatitis, and others. LS was measured by measurements using Fibro Scan, and the median values were used as the final result. Results: In 63 cirrhosis cases, LS was highest in alcoholic cirrhosis. In the 89 cases receiving endoscopy, a significant correlation between LS and the presence or absence of esophageal varices was confirmed (present, 38.2 ± 22.6 kPa; absent, 14.3 ± 11.2 kPa; P

CA-125 Significance in Cirrhosis and Correlation with Disease Severity and Portal Hypertension: A Retrospective Study

Background and Aims: To evaluate the prevalence and significance of elevated cancer antigen-125 (CA-125) levels in patients with cirrhosis being treated in a tertiary care liver center and its correlation with objective markers of disease severity.Methods: We retrospectively reviewed medical records of 172 adult patients with cirrhosis (due to any etiology) after obtaining CA-125 serum analysis. Demographics, etiology of cirrhosis, model of end-stage liver disease (MELD) score, Child’s Turcotte-Pugh classification, albumin bilirubin (ALBI) score, degree of ascites, presence of esophageal varices, serum CA-125 level and various other parameters were collected. Statistical analysis was performed using SPSS software and descriptive statistics.Results: Elevated CA-125 levels were noted in 147 patients (85%) of the study population. Higher MELD score was associated with higher CA-125 levels (p = 0.001). Statistically significant correlation was observed between elevated CA-125 levels and degree of ascites (p < 0.001), ALBI score (p < 0.001) and Child’s Turcotte-Pugh class (p < 0.001). No correlation was observed with presence or absence of esophageal varices. Near-normal CA-125 levels were noted in patients with cirrhosis but undetectable ascites on ultrasound imaging. No differences were observed in mean values between male and female patients (p = 0.207). Regression analysis confirmed that CA-125 levels had a better correlation with degree of ascites than MELD score or ALBI score.Conclusions: Elevated CA-125 levels were noted in 85% of patients with cirrhosis at our center. Our study establishes that the more advanced the degree of decompensation based on MELD score, Child’s Turcotte-Pugh classification and ALBI score, the higher the elevation in CA-125. Absence of ascites was associated with normal CA-125 level, with a direct correlation between high levels and worsening ascites, but there was no statistically significant correlation with esophageal varices, indicating that elevated CA-125 levels could be related to mechanical stretch of the peritoneum rather than portal hypertension itself. Further multi-centered studies are required to confirm and validate these findings.

Absence of Oesophageal Varices in Children with Splenomegaly and Advanced Intestinal Failure Associated Liver Disease

Objectives of the study: Children with splenomegaly and portal hypertension due to primary liver disease demonstrate presence of gastro- oesophageal varices (GOV) on oesophago-gastroduodenoscopy (OGD). Intestinal failure – associated liver disease (IFALD) is a secondary liver disease developing in 40% to 60% of infants requiring long term parenteral nutrition for irreversible intestinal failure. A proportion of these children develop life threatening complications of cirrhosis and portal hypertension. Assessment of portal hypertension is important to determine the type of intestinal transplantation (ITx) offered as a life saving option. Intestinal transplantation is the only life saving option for these children. During intestinal transplant assessment within our programme, we assessed the children for the presence of GOV. Aim: To evaluate the incidence of GOV in children with IFALD referred for small bowel transplant assessment. Methods: Medical records of 122 patients who underwent assessment for small bowel transplant (SBtx) over the last 12 years (Sept 04 to Dec 16) were reviewed. Data detailing spleen size, splenomegaly, liver biopsy with staging of hepatic fibrosis and presence of GOV on oesophago-gastroduodenoscopy (OGD) was recorded. Results: 118/122 children assessed were included in the study as 4 children did not have ultrasound scan (USS). 98/118 (83 %) children had splenomegaly on USS. 54/98 (55.1%) children underwent OGD and oesophageal varices were present in 11 children (20.3%), of which only 10 had Grade 1 and one had Grade 3 varices. Of the 20 patients with a normal sized spleen, 15 underwent an OGD- no varices have been detected. 56 children had an OGD and a liver biopsy performed at the same time. 51/56 patients had fibrosis, 26/51 (50.9 %) were graded as mild fibrosis on liver biopsy, and 8/56 (14.2 %) of them had oesophageal varices (grade 1). Moderate to severe fibrosis was noted in 25/51 (49%) children and only 2/25 (8%) children had GOV, all Grade I. Summary and Conclusion: Children with IFALD, who have a normal size spleen did not have varices at OGD and therefore do not require endoscopy to stage their liver disease. In children with IFALD, splenomegaly is common and GOV are infrequent. Their presence does also not correlate with the degree of liver-fibrosis. In conclusion, USS evidence of splenomegaly alone is a poor predictor for GOV and additional tests such as platelet count, hepatic elastography may improve the assessment of portal hypertension in children with intestinal failure associated liver disease.

Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model.

No published study to date has provided a careful analysis of the effects of a sustained viral response (SVR) on the outcomes of patients with compensated hepatitis C virus (HCV)-related cirrhosis in relation to the degree of portal hypertension. Therefore, we estimated the impact of achieving SVR on disease progression, hepatocellular carcinoma (HCC) development and mortality in a large cohort of HCV patients with cirrhosis with or without oesophageal varices (OVs) at the start of antiviral therapy. A total of 535 Caucasian patients were prospectively recruited to this study. All patients had a clinical or histological diagnosis of compensated HCV-related cirrhosis and underwent interferon-based therapy. Competing risks and a multistate model were analysed according to the presence or absence of OVs at baseline. Compared to patients without SVR, a greater proportion of patients who achieved SVR showed no liver disease progression after 10 years (36.3% vs. 61.3% of patients without baseline OVs; 29.6% vs. 64.3% of patients with baseline OVs). Achievement of SVR was significantly associated with reduced occurrence rates of de-novo OVs, hepatic decompensation and HCC. Compared to patients without SVR, patients with SVR had lower likelihoods of liver-related death at 10 years (20.6% vs. 10.3% of patients without baseline OVs; 50.5% vs. 21.8% of patients with baseline OVs). In patients with compensated HCV-related cirrhosis with or without OVs at baseline, SVR is associated with reduced disease progression and liver-related mortality.

A study of platelet count/ spleen diameter ratio as a predictor of esophageal varices in patients of cirrhosis

Background: Todays guidelines are clear that there are no substitute markers to determine the presence and size of esophageal varices, and endoscopy is still the only valid method to investigate varices. Objective: To validate the PC/SD ratio as a predictor of the presence and absence of esophageal varices in patients with chronic hepatopathy. Methodology: This study is an analytical cross-sectional validation study of a diagnostic test. The study was done in cases diagnosed of having hepatic cirrhosis by histology or physical, biochemical, and imaging examinations compatible with the disease and treatment from February 1, 2013 to December 31, 2014. Various hematological, biochemical and radiological work up was done. Results: Of the total cases, 29(70.7%) had PC/SD ratio more than 909 and only 12(29.3%) had less than 909. The sensitivity of PC/SD ratio of 909 in predicting varix is 89.66% and specificity was 75%. Thus it can be considered a good and reliable tool for predicting varices. Conclusion: The use of platelet count/ splenic diameter ratio in cirrhotic patients for screening and follow up for esophageal varices can substantially reduce the cost of health care and discomfort for patients as well as reduce burden of endoscopy unit.

Is non-invasive diagnosis of esophageal varices in patients with compensated hepatic cirrhosis possible by duplex Doppler ultrasonography?

Esophageal varices are present in 30% to 40% of patients in compensated cirrhosis (Child-Pugh class A) and in 60% to 85% of patients in decompensated cirrhosis (Child-Pugh classes B and C). It is important to identify patients with compensated cirrhosis at risk for esophageal varix development. We evaluated the accuracy of a duplex Doppler ultrasonographic index for predicting the presence or absence of esophageal varices in patients with compensated hepatic cirrhosis (Child-Pugh class A) by using endoscopy as the reference standard. Fifty-six enrolled patients underwent duplex Doppler ultrasonography followed by screening endoscopy. Mean portal vein velocity (PVV), splenic index (SI), splenoportal index (SPI), hepatic and splenic arterial resistive, and pulsatility indices (hepatic artery resistive index [HARI], hepatic artery pulsatility index [HAPI], splenic artery resistive index [SARI], splenic artery pulsatility index [SAPI]) were recorded. Univariate logistic regression analysis was followed by receiver operating characteristic (ROC) curve construction for the indices that were significant. The indices HARI, HAPI, SARI, SAPI were not helpful (p > 0.05). Mean PVV, SI, and SPI were all predictive of the presence of esophageal varices (p < 0.05) and SPI was found to be the most accurate parameter. Of the various cut-off levels of SPI evaluated, a cut-off value of SPI at 5.0, offered the highest diagnostic accuracy (88%). For the 28 patients with SPI <5.0, the absence of esophageal varices in 27 of them could be correctly diagnosed using only SPI without invasive screening endoscopy, with high negative predictive value (96%) and sensitivity (96%). Of the remaining 28 patients with SPI ≥5.0, presence of esophageal varices could be similarly correctly diagnosed in 22 of them by using SPI without screening endoscopy, with high positive predictive value (79%) and specificity (82%). The SPI was accurate in predicting the presence or absence of esophageal varices in patients with compensated cirrhosis.

Long Term Follow up of a Phase 2 Study of Ruxolitinib in Patients with Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasm

Long Term Follow up of a Phase 2 Study of Ruxolitinib in Patients with Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasm

Platelet count to splenic diameter ratio and splenoportal index as non-invasive screening tools in predicting esophageal varices in patients with liver cirrhosis

Abstract Background: Esophageal varices (EVs) are serious consequences of liver cirrhosis. Several studies have evaluated the possible non-invasive markers for the diagnosis of EVs to reduce the number of endoscopic procedures in patients with cirrhosis but without varices. This study was performed to evaluate the diagnostic performance of two such parameters (platelet count to splenic diameter ratio and splenoportal index) for the detection of EVs. Materials and Methods: A total of 111 patients with liver cirrhosis were analyzed after performing upper gastrointestinal endoscopy and non-invasive tests including platelet count and ultrasound abdomen including Doppler study. Appropriate statistical tests were applied to compare the non-invasive tests with the gold standard of endoscopy. Results: Of 111 liver cirrhotics, 80 (72.1%) were male and 31 (27.9%) were female. EVs were present in 68 (61.3%) patients and absent in 43 (38.7%) patients. In platelet count to splenic diameter ratio, a cut-off value of 1014 was obtained, which gave a sensitivity of 75.0%, specificity of 65.1%, positive predictive value (PPV) of 77.3%, negative predictive value (NPV) of 62.2% and diagnostic accuracy of 71.2%. In the splenoportal index, a cut-off value of 3.5 cm/s was obtained, which gave a sensitivity of 79.4%, specificity of 72.0%, PPV of 81.8%, NPV of 68.8% and diagnostic accuracy of 76.5% for the diagnosis of EVs. Conclusions: The platelet count to spleen diameter ratio and splenoportal index are non-invasive and fairly accurate alternatives in identifying the presence or absence of EVs in patients with compensated cirrhosis.

Correlation between Indocyanine green retention test and esophageal varices among patients with hepatocellular carcinoma

We recently read with great interest the manuscript entitled ‘‘Prophylactic impact of endoscopic treatment for esophageal varices in liver resection: a prospective study’’ [1] in which Dr. Yamazaki et al. demonstrated the usefulness of endoscopic prophylactic treatment of esophageal varices (EV) and evaluated different risk factors for post-operative progression and bleeding. The authors observed that in patients with hepatocellular carcinoma (HCC), various laboratory variables were significantly different according to the presence or absence of EV; for example, indocyanine green (ICG) retention rate at 15 min (ICG-r15) was 10.9 % (2.1–37.7) in patients without EV and 15.4 % (3.7–46.0) in patients with EV (P \ 0.001). Finally, they observed that ICG-r15 [ 30 % is independently correlated with the risk of worsening varices. We recently reported our experience [2] aimed to evaluate ICG 15-min retention test as a non-invasive marker of PH and EV in patients with compensated liver cirrhosis in which we demonstrated that among patients with well-preserved liver function, ICG retention tests indirectly correlate with the presence and degree of portal hypertension and its complications (EV). According to the observations of Dr. Yamazaki et al., ICG-r15 correlated with the presence of esophageal varices; we found two different ICG-r15 cut-off points able to accurately rule out and rule in the presence of EV (\10 % and C22.9 %, respectively). Liver-mediated uptake of organic anions (drugs or xenobiotics) is mainly mediated by organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs); ICG presents a potent inhibitor effect on OATP isoforms and Na-taurocholate transporting polypeptide (NTCP). OATP1B3 and NTCP are the transporters involved in the hepatic uptake of ICG [3]. The organic anion transporter peptides (OATP) 1B1 and 1B3 are variably and progressively lost during liver carcinogenesis; a previous study performed on patients who underwent OLT because of HCC demonstrated a correlation between the loss of OATP 1B1/ 1B3 and tumor morphological features [4]. These molecular findings could, in our opinion, justify the higher ICG-r15 values observed by Dr. Yamazaki et al. in their population. Indeed, the ICG retention test, among patients with liver cirrhosis, represents both liver parenchymal reserve and hepatic blood flow; in patients with HCC, this interplay is altered by the introduction of a third variable (cancer biology) and could not be argued. This comment refers to the article available at doi:10.1007/s00535013-0841-y.

Letter to the Editor Haemorrhoidal disease in severe portal hypertension: a combined approach with transjugular intrahepatic portosystemic shunt (TIPS) and transanal haemorrhoidal dearterialization (THD)

Haemorrhoidal disease is a common finding in cirrhotic patients (40–44%) [1, 2], as haemorrhoidal plexus is a possible site of porto-systemic venous anastomosis. Portal hypertension (PH) can both exacerbate pre-existent essential haemorrhoidal varices (HV) and cause secondary vascular pathologies, called ano-rectal varices (ARV), particularly in conditions of severely increased hepatic vein pressure gradient (HVPG). Coexisting in up to 30% of cases, ARV are different from HV: as they are mainly due to portal pressure, they usually do not benefit from local therapies, requiring instead a corrective strategy for the underlying PH. Here we report a case of a 45-year-old man, known to have alcoholic Child-B liver cirrhosis, who was admitted to our clinic in March 2011 for severe anaemization (haemoglobin 5.8 g/dl) secondary to persistent rectorrhagia. On admission, he was haemodynamically stable and physical examination evidenced pale skin, tachycardia and tachypnoea, while laboratory results showed microcytic anaemia and severe thrombocytopenia (46 000/µl), and mild elevation of hepatic tests. On anamnestic deepening, he underwent an haemorrhoidal prolapsectomy 15 years earlier and a haemorrhoidal ligature 6 years earlier for persistent symptomatic bleeding haemorrhoids. Moreover, he had a 25-year history of severe alcohol consumption but he had been in a relatively good condition until August 2010, when he received the diagnosis of liver cirrhosis because of the first episode of hepatic decompensation (ascites and encephalopathy). Clinical examination evidenced third-degree haemorrhoids and a pancolonoscopy documented ARV excluding other colonic bleeding lesions, while upper endoscopy showed congestive gastropathy in absence of oesophageal varices. Doppler ultrasonography revealed an increased diameter of the main portal tract (13.5 mm), with preserved hepatopetal flow at reduced mean velocity (10 cm/s). An abdominal computed tomography scan with contrast medium detected a patent ectatic superior mesenteric vein with congestion of the rectal venous plexus and mild perihepatic ascites and splenomegaly (Figure 1). Repeated blood transfusions were prescribed to raise haemoglobin and propranolol in increasing dosage was started to reduce portal hypertension. However, severe rectorrhagia continued so we opted for reducing portal system congestion with a transjugular intrahepatic portosystemic shunt (TIPS). The initial portal venous pressure was 22 mm Hg and the estimated HVPG was 18 mm Hg. Despite reduction of the pressure gradient from 18 mm Hg to 4 mm Hg, rectorrhagia persisted, so surgical intervention for haemorrhoids was suggested. Transanal haemorrhoidal dearterialization (THD) was performed through a dedicated proctoscope, which incorporates a Doppler probe that allows one to identify and to ligate haemorrhoidal arteries and arteriovenous shunts. Transanal haemorrhoidal dearterialization is an innovative mini-invasive technique that has gradually gained in popularity among surgeons since the encouraging initial results reported by Morinaga et al. [3] in 1995. It consists of the Doppler-guided ligation of the terminal branches of the superior rectal artery, which solely contribute to the blood supply of the haemorrhoidal plexus [4, 5], thereby reducing the congestion [6]. The postoperative course was uneventful and the patient was discharged after 5 days. After a 15-month follow-up period, the patient is in good clinical condition, complying with his medical treatment, and the ano-rectal blood loss has not recurred. Figure 1 Coronal contrast-enhanced CT image showing ectatic superior mesenteric vein (white arrow) This case highlights how difficult it can be to diagnose and treat haemorrhoidal disease in cirrhotic patients with severe portal hypertension. The presence of persistent bleeding HV, relapsing after previous local therapies, and of endoscopic-evident ARV, suggested that the severely increased portal hypertension was the real cause of bleeding and of persistence of varices. So, we first reduced portal hypertension with both medical (β-blockers) and interventional (TIPS) techniques, probably achieving a reduction in ARV degree and, when we observed that rectorrhagia persisted, it was clear that blood loss was due to coexistent essential HV, this time. Thus, we treated them with a local mini-invasive technique (THD, previously described). Conventional surgical approaches are usually considered unsuitable in this context [7]: they can worsen portal hypertension after surgical removal of the venous porto-caval shunts, as well as having an increased risk of complications in cirrhotic patients. In conclusion, our experience sheds further light on the relevance of managing portal pressure in case of persistent bleeding and relapsing HV in presence of ARV: TIPS could be performed as the first approach in order to reduce the degree of portal hypertension and to plan, in case of ineffective resolution of ano-rectal bleeding, a mini-invasive surgical procedure with reduced operative risk.