Development Of Variceal Bleeding Research Articles

ASSOCIATION OF VARICEAL BLEED WITH SEVERITY OF LIVER CIRRHOSIS AT A TERTIARY CARE HOSPITAL

Background; A major cause of cirrhosis-related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Each episode of active variceal bleeding is associated with 30 percent mortality. This study was planned to determine frequency of variceal bleeding in patients with liver cirrhosis and frequency of in-hospital mortality of these patients in our population. Objective; To determine the frequency of variceal bleed in hospitalized patients with cirrhosis of liver and its outcome in terms of in-hospital mortality. Material and Methods; Consecutive 139 Patient diagnosed with cirrhosis of liver were included in this cross-sectional study from department of Medicine, Bahawal Victoria hospital Bahawalpur. Complete history and physical examination was assessed to document duration of duration of liver disease, ascites, Hepatic encephalopathy, Previous GI bleed and systemic coagulopathy. All the patients had undergone diagnostic upper GI endoscopic examination to document varices. Results; Of these 139 study cases, 77 (55.4 %) were male and 62 (44.6 %) were female. Mean age of our study cases was 45.50 ± 10.81 years. Mean duration of disease (liver cirrhosis) was 3.25 ± 2.32 years. Majority of our study cases i.e. 94 (67.6%) were having liver cirrhosis for the duration of less than 5 years. Child-Pugh class C was more prevalent i.e. 77 (55.4%) of our study cases. Variceal bleeding was observed in 100 (71.9 %) of our study cases. Frequency of mortality was 35 (25.2%) in our study cases with liver cirrhosis, while frequency of mortality in patients with variceal bleeding was seen in 31 (31%). Variceal bleeding was significantly associated with disease severity (p<0.001). Conclusion; Very high frequency of variceal bleeding was observed in patients with liver cirrhosis. In-hospital mortality was significantly more prevalent in patients with variceal bleeding than without bleed. Variceal bleeding was significantly more seen in patients with increasing age, duration of disease and with more severe level of disease (Child Pugh class C). There was no statistically significant difference of bleeding with regards to gender. Keywords; Liver Cirrhosis, Variceal bleeding, Mortality. DOI : 10.7176/JMPB/62-13 Publication date: December 31 st 2019

Hepatitis C eradication with direct-acting anti-virals reduces the risk of variceal bleeding.

The real-world, long-term benefits of sustained virologic response (SVR) on the risk of variceal bleeding remain unclear. To assess the association between DAA-induced SVR and post-treatment variceal bleeding METHODS: We identified patients who initiated DAA-only anti-viral treatments in the United States Veterans Affairs healthcare system from 2013 to 2015. We followed patients until 1 January 2019 for the development of gastro-oesophageal variceal bleeding defined by diagnostic codes. We used multivariable Cox proportional hazards regression to assess the association between SVR and development of variceal bleeding, adjusting for potential confounders. Among 33582 DAA-treated patients, 549 (1.6%) developed variceal bleeding after treatment (mean follow-up 3.1years). Compared to no SVR, SVR was associated with a significantly lower incidence of variceal bleeding among all patients (0.46 vs 1.26 per 100 patient-years, adjusted hazard ratio [AHR] 0.66, 95% CI 0.52-0.83), among patients with pre-treatment cirrhosis (1.55 vs 2.96 per 100 patient-years, AHR 0.73, 95% CI 0.57-0.93) and among patients without pre-treatment cirrhosis (0.07 vs 0.29 per 100 patient-years, AHR 0.33, 95% CI 0.17-0.65). The risk of variceal bleeding after treatment was lower in those who achieved SVR vs no SVR among patients who had non-bleeding varices (3.5 vs 4.9 per 100 patient-years) or bleeding varices (12.9 vs 16.4 per 100 patient-years) diagnosed before treatment, but these differences were not statistically significant in adjusted analyses. DAA-induced SVR is independently associated with a lower risk of variceal bleeding during long-term follow-up in patients with and without pre-treatment cirrhosis. These findings demonstrate an important real-world benefit of DAA treatment.

DIABETES AS A PREDICTOR OF MORTALITY IN CIRRHOTIC PATIENTS PRESENTING WITH VARICEAL BLEED

Background; A major cause of cirrhosis-related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Each episode of active variceal bleeding is associated with 30 percent mortality. This study was planned to determine frequency of variceal bleeding in patients with liver cirrhosis and frequency of in-hospital mortality of these patients in our population. Objective; To determine association of diabetes with mortality in patients with liver cirrhosis presenting with of variceal bleed. Material and Methods; Consecutive 139 Patient diagnosed with cirrhosis of liver were included in this cross-sectional study from department of Medicine, Nishtar hospital Multan. Complete history and physical examination was assessed to document duration of duration of liver disease, ascites, Hepatic encephalopathy, Previous GI bleed and systemic coagulopathy. All the patients had undergone diagnostic upper GI endoscopic examination to document varices. Results; Of these 139 study cases, 77 (55.4 %) were male and 62 (44.6 %) were female. Mean age of our study cases was 45.50 ± 10.81 years. Mean duration of disease (liver cirrhosis) was 3.25 ± 2.32 years. Majority of our study cases i.e. 94 (67.6%) were having liver cirrhosis for the duration of less than 5 years. Child-Pugh class C was more prevalent i.e. 77 (55.4%) of our study cases. Variceal bleeding was observed in 100 (71.9 %) of our study cases. Frequency of diabetes in cirrhotic patients with variceal bleed was 47 (33.81%) and mortality in these diabetics was 26 (55.31%) (p = 0.001). Conclusion; Diabetes was found to be significantly associated with mortality in cirrhotic patients presenting with variceal bleeding. Healthcare professionals should anticipate adverse outcomes in diabetic patients of liver cirrhosis presenting with variceal bleeding and should educate them regarding glycemic control at early stages of diagnosis. Keywords; Liver Cirrhosis, Variceal bleeding, Mortality. DOI : 10.7176/JMPB/58-01 Publication date : August 31 st 2019

Endocannabinoid System in Hepatic Glucose Metabolism, Fatty Liver Disease, and Cirrhosis.

There is growing evidence that glucose metabolism in the liver is in part under the control of the endocannabinoid system (ECS) which is also supported by its presence in this organ. The ECS consists of its cannabinoid receptors (CBRs) and enzymes that are responsible for endocannabinoid production and metabolism. ECS is known to be differentially influenced by the hepatic glucose metabolism and insulin resistance, e.g., cannabinoid receptor type 1(CB1) antagonist can improve the glucose tolerance and insulin resistance. Interestingly, our own study shows that expression patterns of CBRs are influenced by the light/dark cycle, which is of significant physiological and clinical interest. The ECS system is highly upregulated during chronic liver disease and a growing number of studies suggest a mechanistic and therapeutic impact of ECS on the development of liver fibrosis, especially putting its receptors into focus. An opposing effect of the CBRs was exerted via the CB1 or CB2 receptor stimulation. An activation of CB1 promoted fibrogenesis, while CB2 activation improved antifibrogenic responses. However, underlying mechanisms are not yet clear. In the context of liver diseases, the ECS is considered as a possible mediator, which seems to be involved in the synthesis of fibrotic tissue, increase of intrahepatic vascular resistance and subsequently development of portal hypertension. Portal hypertension is the main event that leads to complications of the disease. The main complication is the development of variceal bleeding and ascites, which have prognostic relevance for the patients. The present review summarizes the current understanding and impact of the ECS on glucose metabolism in the liver, in association with the development of liver cirrhosis and hemodynamics in cirrhosis and its complication, to give perspectives for development of new therapeutic strategies.

Management of portal hypertensive gastropathy and other bleeding.

A major cause of cirrhosis related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Less common causes of gastrointestinal bleeding are peptic ulcers, malignancy, angiodysplasia, etc. Upper gastrointestinal bleeding has been classified according to the presence of a variceal or non-variceal bleeding. Although non-variceal gastrointestinal bleeding is not common in cirrhotic patients, gastroduodenal ulcers may develop as often as non-cirrhotic patients. Ulcers in cirrhotic patients may be more severe and less frequently associated with chronic intake of non-steroidal anti-inflammatory drugs, and may require more frequently endoscopic treatment. Portal hypertensive gastropathy (PHG) refers to changes in the mucosa of the stomach in patients with portal hypertension. Patients with portal hypertension may experience bleeding from the stomach, and pharmacologic or radiologic interventional procedure may be useful in preventing re-bleeding from PHG. Gastric antral vascular ectasia (GAVE) seems to be different disease entity from PHG, and endoscopic ablation can be the first-line treatment.

Portal Hypertension–Related Complications After Acute Portal Vein Thrombosis: Impact of Early Anticoagulation

Acute portal vein thrombosis (APVT) is a rare disorder that causes chronic portal hypertension if recanalization is not obtained. However, response to anticoagulation and long-term prognosis of APVT are not well-defined. Thirty-eight patients diagnosed with APVT between 1995 and 2003 from 5 Spanish referral hospitals, in whom cirrhosis and malignancy were specifically excluded, were included in this retrospective study. The response to anticoagulation therapy and development of portal hypertension-related complications during follow-up were evaluated. Mean follow-up was 43 months (range, 6-112 months). Recanalization occurred in 12 of 27 patients receiving anticoagulation versus 0 of 11 patients who did not receive anticoagulation (P = .008). Rates of recanalization were influenced by the precocity of heparin administration and the number of underlying prothrombotic conditions. Follow-up upper endoscopy performed in 29 patients disclosed gastroesophageal varices in 16 (55%). Varices appeared as early as 1 month after APVT. However, in most patients varices were detected in successive endoscopies, mainly during the first year. Two-year actuarial probability of variceal bleeding was 12% and for ascites 16%. Five-year survival was 87%. Mortality was related to the APVT episode in 2 cases and to an underlying hematologic disorder in one. Anticoagulation achieved recanalization in about 40% of patients. Most patients not achieving recanalization will develop gastroesophageal varices during follow-up. However, development of variceal bleeding and ascites is infrequent, and survival is satisfactory.

Management of patients with liver disease on the intensive care unit

There are two groups of patients with liver disease who may be found on an intensive care unit: those with chronic liver disease (CLD), and those with fulminant hepatic failure (FHF) and late onset hepatic failure. Many of the problems and haemodynamic abnormalities are common to both groups; however, there are specific differences, in particular the development of cerebral oedema in patients with FHF and the development of variceal bleeding in patients with CLD. Fulminant hepatic failure is the term used to describe patients with a very rapid progression of symptoms and signs, normally defined as the onset of encephalopathy within 8 weeks of the development of symptoms (Trey and Davidson, 1970) in patients without preceding liver disease. A similar group of patients is those with late onset hepatic failure (LOHF), defined as the onset of encephalopathy within 8 weeks to 6 months of the development of jaundice, again in patients without preceding liver disease (Gimson et al, 1986). The stratification of patients with respect to speed of onset of encephalopathy is of great importance since this in association with aetiology carries prognostic implications; this is a point of special importance when transplantation is being considered as a therapeutic option (O'Grady et al, 1989). AETIOLOGY

Morphometric study of the esophageal mucosa in cirrhotic patients with variceal bleeding.

A morphometric study of the distal esophageal mucosa (within 5 cm above the gastroesophageal junction) has been carried out in a group of 11 cirrhotic patients undergoing esophageal transection with SPTU gun for variceal bleeding. The relative thickness of the papillae (62.2 +/- 3.9%) and basal zone (11.8 +/- 1.9%) were within normal limits. Polymorphonuclear infiltrates were not found either in the lamina propria or in the epithelium. The absence of histopathologic changes in the esophageal mucosa from patients with liver cirrhosis and bleeding esophageal varices confirms the hypothesis that gastroesophageal reflux does not play a pathogenic role in the development of variceal bleeding.

Lower Esophageal Sphincter Pressure in Cirrhotic Men with Ascites: Before and After Diuresis

Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding.