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1.  The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study 
BMC Gastroenterology  2009;9:50.
Despite its biologic plausibility, the association between liver function and mortality of patients with chronic liver disease is not well supported by data. Therefore, we examined whether the galactose elimination capacity (GEC), a physiological measure of the total metabolic capacity of the liver, was associated with mortality in a large cohort of patients with newly-diagnosed cirrhosis.
By combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis in 1992–2005. We divided the patients into 10 equal-sized groups according to GEC and calculated all-cause mortality as well as cirrhosis-related and not cirrhosis-related mortality for each group. Cox regression was used to adjust the association between GEC and all-cause mortality for confounding by age, gender and comorbidity, measured by the Charlson comorbidity index.
We included 781 patients, and 454 (58%) of them died during 2,617 years of follow-up. Among the 75% of patients with a decreased GEC (<1.75 mmol/min), GEC was a strong predictor of 30-day, 1-year, and 5-year mortality, and this could not be explained by confounding (crude hazard ratio for a 0.5 mmol/min GEC increase = 0.74, 95% CI 0.59–0.92; adjusted hazard ratio = 0.64, 95% CI 0.51–0.81). Further analyses showed that the association between GEC and mortality was identical for patients with alcoholic or non-alcoholic cirrhosis etiology, that it also existed among patients with comorbidity, and that GEC was only a predictor of cirrhosis-related mortality. Among the 25% of patients with a GEC in the normal range (≥ 1.75 mmol/min), GEC was only weakly associated with mortality (crude hazard ratio = 0.79, 95% CI 0.59–1.05; adjusted hazard ratio = 0.80, 95% CI 0.60–1.08).
Among patients with newly-diagnosed cirrhosis and a decreased GEC, the GEC was a strong predictor of short- and long-term all-cause and cirrhosis-related mortality. These findings support the expectation that loss of liver function increases mortality.
PMCID: PMC2721849  PMID: 19566919
2.  Therapy for alcoholic liver disease 
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.
PMCID: PMC3942819  PMID: 24605013
Alcoholic liver disease; Alcoholic steatosis; Alcoholic hepatitis; Alcoholic cirrhosis; Alcoholism; Liver disease; Corticosteroids; Pentoxifylline; Liver transplantation
3.  Hyponatremia influences the outcome of patients with acute-on-chronic liver failure: an analysis of the CANONIC study 
Critical Care  2014;18(6):700.
Hyponatremia is a marker of poor prognosis in patients with cirrhosis. This analysis aimed to assess if hyponatremia also has prognostic value in patients with acute-on-chronic liver failure (ACLF), a syndrome characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality.
We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,341 consecutive patients admitted to 29 European centers with acute decompensation of cirrhosis (including ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infections, or any combination of these), both with and without associated ACLF (301 and 1,040 respectively).
Of the 301 patients with ACLF, 24.3% had hyponatremia at inclusion compared to 12.3% of 1,040 patients without ACLF (P <0.001). Model for end-stage liver disease, Child-Pugh and chronic liver failure-SOFA scores were significantly higher in patients with ACLF and hyponatremia compared to those without hyponatremia. The presence of hyponatremia (at inclusion or during hospitalization) was a predictive factor of survival both in patients with and without ACLF. The presence of hyponatremia and ACLF was found to have an independent effect on 90-day survival after adjusting for the potential confounders. Hyponatremia in non-ACLF patients nearly doubled the risk (hazard ratio (HR) 1.81 (1.33 to 2.47)) of dying at 90 days. However, when considering patients with both factors (ACLF and hyponatremia) the relative risk of dying at 90 days was significantly higher (HR 6.85 (3.85 to 12.19) than for patients without both factors. Patients with hyponatremia and ACLF had a three-month transplant-free survival of only 35.8% compared to 58.7% in those with ACLF without hyponatremia (P <0.001).
The presence of hyponatremia is an independent predictive factor of survival in patients with ACLF. In cirrhosis, outcome of patients with ACLF is dependent on its association with hyponatremia.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-014-0700-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4280050  PMID: 25643318
4.  Retrospective Study of the Clinical Profile and Prognostic Indicators in Patients of Alcoholic Liver Disease Admitted to a Tertiary Care Teaching Hospital in Western Nepal 
Alcohol is the most common substance abused in Nepal. Liver disease caused by alcohol abuse, including its end stage, cirrhosis, is a major health care problem, which is difficult to treat.
To study the demographic profile, laboratory parameters, complications and their prognostic implications among patients of alcoholic liver disease (ALD).
Materials and Methods:
Records of all patients of ALD admitted from January 1' 2005 to December 31' 2006 were studied and followed up to December 31, 2007. A total of 181 patients were analyzed. Their clinical profile and laboratory parameters were noted and analyzed using SPSS-10.0 software.
Among the 181 patients, 80.7% were male, 30.9% were army/ex-army and 65.2% were documented smokers. The mean age of presentation was 52.08 years. Jaundice (57.5%) was the most common presentation followed by hepatomegaly (51.4%). Hypoalbuminemia (50.3) followed by ascites (48.1) were common complications. Death occurred in 19.1% of the patients, the most common cause being hepatic encephalopathy (72.2%) followed by variceal bleeding and hepatorenal syndrome. Jaundice, ascites and hepatic encephalopathy at presentation and female sex were significantly associated with increased mortality along with discriminant score >32, aspartate aminotransferase (AST): Alanine aminotranferase (ALT) ≥ 2, ultrasonography (USG)-proven cirrhosis, rise in prothrombin time ≥5 s, total bilirubin ≥ 4mg/dL and ESR ≥34.
ALD was predominantly seen among the productive age group with a high morbidity and mortality. Jaundice, ascites, hepatic encephalopathy at presentation and female sex are poor prognostic indicators along with discriminant score > 32, AST:ALT ≥ 2, USG-proven cirrhosis, coagulopathy, hyperbilirubenemia and high ESR.
PMCID: PMC2841416  PMID: 19636178
Alcoholic liver disease; demographic profile; prognostic indicators; Nepal
5.  Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding 
Gut  1999;44(2):264-269.
Background—Height of portal pressure correlates with severity of alcoholic cirrhosis. Portal pressure indices are not however used routinely as predictors of survival. 
Aims—To examine the clinical value of a single portal pressure measurement in predicting outcome in cirrhotic patients who have bled. 
Methods—A series of 105 cirrhotic patients who consecutively underwent hepatic venous pressure measurement were investigated. The main cause of cirrhosis was alcoholic (64.8%) and prior to admission all patients had bled from varices. 
Results—During the follow up period (median 566 days, range 10-2555), 33 patients died, and 54 developed variceal haemorrhage. Applying Cox regression analysis, hepatic venous pressure gradient, bilirubin, prothrombin time, ascites, and previous long term endoscopic treatment were the only statistically independent predictors of survival, irrespective of cirrhotic aetiology. The predictive value of the pressure gradient was much higher if the measurement was taken within the first or the second week from the bleeding and there was no association after 15 days. A hepatic venous pressure gradient of at least 16 mm Hg appeared to identify patients with a greatly increased risk of dying. 
Conclusions—Indirectly measured portal pressure is an independent predictor of survival in patients with both alcoholic and non-alcoholic cirrhosis. In patients with a previous variceal bleeding episode this predictive value seems to be better if the measurement is taken within the first two weeks from the bleeding episode. A greater use of this technique is recommended for the prognostic assessment and management of patients with chronic liver disease. 

Keywords: chronic liver disease; alcoholic cirrhosis; portal pressure
PMCID: PMC1727391  PMID: 9895388
6.  Variceal hemorrhage: Saudi tertiary center experience of clinical presentations, complications and mortality 
World Journal of Hepatology  2012;4(9):268-273.
AIM: To determine the clinical presentation, underlying etiology and short- and long-term outcomes of acute variceal bleeding (AVB).
METHODS: A retrospective descriptive cohort study of cirrhotic patients with AVB who were admitted to King Abdul Aziz University Hospital between January 2005 and December 2009. We obtained demographic data for all patients. For each patient we also obtained the clinical data at presentation; cause of liver cirrhosis, bleeding presentation (hematemesis and/or melena), presence of ascites, hepatic encephalopathy and renal impairment (RI) or hepatorenal syndrome. We carried out complete blood count, prothrombin time evaluation, and liver function tests. We also report all episodes of re-bleeding after the first episode of AVB, both during the initial admission and after discharge. We recorded the length of stay for each patient and thereby calculated the mean duration of stay for all patients. The length of follow-up after the first AVB and the outcome for each patient at the end of the study period were recorded. Causes of mortality either related to liver disease or non-liver disease cause were determined.
RESULTS: A 125 patients were enrolled in the study. The number of episodes of AVB for each patients varied between 1 and 10. Survival from the first attack of AVB to death was 20.38 mo (SD 30.86), while the length of follow-up for the living patients was 53.58 mo (SD 24.94). Total number of AVB admissions was 241. Chronic hepatitis C, the commonest underlying etiology for liver disease, was present in 46 (36.8%) patients. Only 35 (28%) patients had received a primary prophylactic β-blocker before the first bleeding episode. The mean hemoglobin level at the time of admission was 8.59 g/dL (SD 2.53). Most patients had Child-Pugh Class C 41 (32.8%) or Class B 72 (57.6%) disease. Hematemesis was the predominant symptom and was found in 119 (95.2%) patients, followed by melena in 75 (60.0%) patients. Ascites of variable extent was documented in 93 (74.4%) patients. We identified hepatic encephalopathy in 31 (28.8%) patients and spontaneous bacterial peritonitis in 17 (13.6%). Bleeding gastric varices was the cause of AVB in 2 patients. AVB was associated with shock in 22 patients, 13 of whom (59.1%) had Child-Pugh class C disease. RI was noted in 19 (46.3%) of 41 patients in Child-Pugh class C and 14 (19.4%) of 72 patients in Child-Pugh class B. None of the patients with Child-Pugh class A disease had RI. Emergency endoscopy was effective in controlling the bleeding, although the re-bleeding rate was still high, 12 (9.6%) during the same admission and 55 (44%) after discharge. The re-bleeding rate was higher in patients with ascites, occurring in 40/55 (72.2%). The length of hospital stay was 1-54 d with a mean of 8.7 d. Three patients had emergency surgery due to failure of endoscopic treatment and balloon tamponade. The overall long term mortality was 65%. Survival from the first attack of AVB to death was 20.38 ± 30.86 mo, while the length of follow-up for the living patients was 53.58 ± 24.94 mo. Patients with Child-Pugh score C had a higher risk of liver disease-related mortality (67.6%). RI (developed during admission) was the main factor that was associated with mortality (P = 0.045).
CONCLUSION: The majority of patients with liver disease who present at the emergency unit for AVB are at an advanced stage of the disease. The outcome is poorer for patients who develop RI during hospitalization.
PMCID: PMC3468704  PMID: 23060972
Endoscopy; Liver disease; Mortality; Outcome; Varices; Variceal bleeding
7.  Hyponatremia in Cirrhosis and End-Stage Liver Disease: Treatment with the Vasopressin V2-Receptor Antagonist Tolvaptan 
Digestive Diseases and Sciences  2012;57(11):2774-2785.
Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V2-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.
PMCID: PMC3472061  PMID: 22732834
Arginine vasopressin; MELD score; Portal hypertension; Vasopressin receptor antagonists
8.  Longterm follow up of transjugular intrahepatic portosystemic stent shunt (TIPSS) for the treatment of portal hypertension: results in 130 patients. 
Gut  1996;39(3):479-485.
BACKGROUND: Transjugular intrahepatic portosystemic stent shunts (TIPSS) are increasingly being used to manage the complications of portal hypertension. This study reports on the follow up on 130 patients who have undergone TIPSS. PATIENTS AND METHODS: One hundred and thirty patients (81 male), mean (SD) age 54.7 (12.5) years underwent TIPSS. The majority (64.6%) had alcoholic cirrhosis and 53.2% had Childs C disease. Indications were: variceal haemorrhage (76.2%), refractory ascites (13.1%), portal hypertensive gastropathy (4.6%), others (6.1%). Shunt function was assessed by Doppler ultrasonography and two then six monthly portography and mean follow up for survivors was 18.0 months (range 2-43.5). RESULTS: The procedure was successful in 119 (91.5%). Sixty three episodes of shunt dysfunction were observed in 45 (37.8%) patients. Variceal rebleeding occurred in 16 (13.4%) patients and was always associated with shunt dysfunction. Twenty (16.8%) patients had new or worse spontaneous encephalopathy after TIPSS and 11 (64.7%) patients had an improvement in resistant ascites. Thirty day mortality was 21.8% and one year survival 62.5%. CONCLUSION: TIPSS is an effective treatment for variceal bleeding, resistant ascites, and portal hypertensive gastropathy. Rebleeding is invariably associated with shunt dysfunction, the frequency of which increases with time, therefore regular and longterm shunt surveillance is required.
PMCID: PMC1383360  PMID: 8949658
9.  Hospital Re-Admissions among Patients with Decompensated Cirrhosis 
Early re-hospitalizations have been well characterized in many disease states, but not among patients with cirrhosis. The aims of this study were to identify the frequency, costs, predictors, and preventable causes of hospital re-admissions among patients with decompensated cirrhosis.
Rates of re-admission were calculated for 402 patients discharged after one of the following complications of cirrhosis: ascites, spontaneous bacterial peritonitis, renal failure, hepatic encephalopathy or variceal hemorrhage. Costs of re-admissions were calculated using the hospital accounting system. Predictors of time to first re-admission were determined using Cox regression, and predictors of hospitalization rate/person-years using negative binomial regression. The independent association between re-admission rate and mortality was determined using Cox regression. Admissions within 30 days of discharge were assessed by two reviewers to determine if preventable.
276 (69%) subjects had at least one non-elective re-admission, with a median time to first re-admission of 67 days. By one week after discharge 14% of subjects had been re-admitted, and 37% were re-admitted within one month. The mean costs for re-admissions within one week and between weeks 1–4 were $28,898 and %20,581, respectively. During a median follow-up of 203 days, the median number of re-admissions was 2 (range 0–40), with an overall rate of 3 hospitalizations/person-years. Patients with more frequent re-admissions had higher risk of subsequent mortality, despite adjustment for confounders including the Model for End-stage Liver Disease score. Predictors of time to first re-admission included MELD score, serum sodium, and number of medications on discharge; predictors of hospitalization rate included these variables as well as the number of cirrhosis complications and being on the transplant list at discharge. Among 165 re-admissions within 30 days, 22% were possibly preventable.
Hospital re-admissions among patients with decompensated cirrhosis are common, costly, moderately predictable, in some cases possibly preventable, and independently associated with mortality. These findings support the development of disease management interventions to prevent re-hospitalization.
PMCID: PMC3470789  PMID: 21931378
10.  CIRRHOSIS OF THE LIVER—Clinical Course in 2,377 Patients at San Francisco General Hospital 
California Medicine  1961;94(6):353-356.
The records of 2,377 patients with Laennec's cirrhosis were reviewed for the period 1947-1957. The chief presenting symptom was ascites in 46 per cent, bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both jaundice and ascites in 4 per cent. Nearly half of the patients died during the period under study—one-third from hepatic failure, one-third from gastrointestinal bleeding, and one-third from other causes, most of which were related to alcoholism.
Massive gastrointestinal bleeding occurred in 21 per cent of the patients at some time in their clinical course, and in the 10 per cent of these in whom ulcer was demonstrated, one-fifth died as a result of the hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per cent of all those who bled from varices were dead at the end of one year, and 91 per cent were dead at the end of three years.
The survival curve of a group of patients who bled once and were good operative risks but had received no operative treatment was compared to the survival curve for entire group who survived the first hemorrhage. The three-year survival in the good risk group was 47 per cent; for the group as a whole it was 30 per cent. The difference in mortality rate was primarily due to an increased number of deaths from hepatic failure in the combined group, whereas 60 per cent of the good risk group died of recurrent gastrointestinal hemorrhage.
As 86 per cent of those who were to die of gastrointestinal bleeding did so at the first hemorrhage, it was concluded that any decided improvement in the salvage rate achievable by operation must come from some means of diagnostic forecast of the likelihood of bleeding, with resort to prophylactic operation in such cases.
PMCID: PMC1574429  PMID: 18732405
11.  Management of Acute Variceal Bleeding 
Clinical Endoscopy  2014;47(4):308-314.
Acute variceal bleeding could be a fatal complication in patients with liver cirrhosis. In patients with decompensated liver cirrhosis accompanied by ascites or hepatic encephalopathy, acute variceal bleeding is associated with a high mortality rate. Therefore, timely endoscopic hemostasis and prevention of relapse of bleeding are most important. The treatment goals for acute variceal bleeding are to correct hypovolemia; achieve rapid hemostasis; and prevent early rebleeding, complications related to bleeding, and deterioration of liver function. If variceal bleeding is suspected, treatment with vasopressors and antibiotics should be initiated immediately on arrival to the hospital. Furthermore, to obtain hemodynamic stability, the hemoglobin level should be maintained at >8 g/dL, systolic blood pressure >90 to 100 mm Hg, heart rate <100/min, and the central venous pressure from 1 to 5 mm Hg. When the patient becomes hemodynamically stable, hemostasis should be achieved by performing endoscopy as soon as possible. For esophageal variceal bleeding, endoscopic variceal ligation is usually performed, and for gastric variceal bleeding, endoscopic variceal obturation is performed primarily. If it is considered difficult to achieve hemostasis through endoscopy, salvage therapy may be carried out while keeping the patient hemodynamically stable.
PMCID: PMC4130884  PMID: 25133116
Acute variceal bleeding; Hemostasis; Endoscopy
12.  Hyponatremia – predictor of adverse prognosis in cirrhosis 
Journal of Medicine and Life  2012;5(2):176-178.
Hyponatremia is a frequent complication of the advanced liver disease, being, as the hepatorenal syndrome, a consequence of the important circulatory dysfunction of cirrhosis. Hyponatremia is determined by the impaired capacity of the kidney to excrete free water, which leads to water retention disproportionate to sodium retention, thus causing low plasma osmolarity. Hyponatremia in cirrhosis is associated with a high morbidity and mortality, its presence suggesting a very advanced liver disease. Current evidence suggests that hyponatremia affects the brain function and predisposes to hepatic encephalopathy. In addition, hyponatremia is a risk factor for liver transplantation, being associated with a high frequency of complication and affecting short and long-term post-transplant survival.
PMCID: PMC3391887  PMID: 22802886
hyponatremia; hypo-osmolarity; circulatory dysfunction; hepatorenal syndrome
13.  Surgery for Variceal Bleeding in Cirrhosis: A Review of Our Experience and Present Concepts 
The major cause of portal hypertension in Western countries is nutritional cirrhosis (parenchymal block) related to alcoholism. A third of those patients die of variceal bleeding when increased pressure within the varices precipitates bleeding. Construction of portal systemic shunts is aimed at reducing the pressure within the varices and thereby decreasing the risk of bleeding. However, it increases the incidence of hepatic encephalopathy and hence should be used only in patients who have bled. The remaining function appears to be the main factor that determines survival and the incidence of encephalopathy in obese individuals. Portacaval shunts almost completely eliminate the risk of bleeding. There is a greater incidence of hepatic encephalopathy with this procedure than with other shunts. The splenorenal shunt and the distal splenorenal shunt appear to work well in selected patients. Technically, it is a more difficult procedure. The interposition mesocaval shunt is technically easier and is also helpful in patients with ascites. Its post-shunt encephalopathy rate, however, is higher than the splenorenal shunt or the distal splenorenal shunt, though less than the portacaval shunts. Experience with the newer arterialized portacaval and coronary caval shunts is limited. A non-shunt procedure, such as the one described by Sugiura, with impressive results and follow-up may become more acceptable as experience grows.
PMCID: PMC2537278  PMID: 312948
14.  Endoscopic sclerotherapy using absolute alcohol. 
Gut  1985;26(2):120-124.
To assess the efficacy of absolute alcohol as a sclerosant, endoscopic sclerotherapy was carried out using a conventional endoscope and an indigenously designed injector. Forty three patients with portal hypertension who had presented with history of variceal bleeding were included in the study. Portal hypertension was caused by cirrhosis in 30 (69.8%), non-cirrhotic portal fibrosis in eight (18.6%) and extra-hepatic obstruction in five (11.8%). Acute bleeding was successfully controlled in all 11 patients, seven with a fresh bleed and four who rebled while on endoscopic sclerotherapy regimen. All patients with fresh, recent, or old bleeding were treated with a weekly endoscopic sclerotherapy schedule. Reduction in variceal size of two or more grades was achieved in all 20 patients who had completed at least four endoscopic sclerotherapy courses with total eradication of varices in 16 (80%). The mean (+/- SD) number of endoscopic sclerotherapy courses and time required for variceal eradication was 6.06 (+/- 1.87) and 9.1 (+/- 4.69) weeks respectively. None of these patients has shown appearance of fresh varices in a follow up of 18.47 +/- 8.50 weeks (range six to 38 weeks). Six patients died; all deaths were caused by progressive hepatic encephalopathy. Complications usually seen were dysphagia, retrosternal pain and fever; these were mild and easily tolerated by the patients. Rebleeding occurred in four patients who had received less than four endoscopic sclerotherapy courses. Absolute alcohol appears to be an effective, safe, economical, and freely available sclerosant. advocate endoscopic sclerotherapy as the first line of treatment for acute variceal bleeding and recommend a weekly schedule for the early eradication of varices.
PMCID: PMC1432418  PMID: 3871416
15.  The Warren Shunt in Treating Bleeding Esophageal Varices 
Western Journal of Medicine  1979;130(4):304-308.
In patients who have impaired hepatic reserve, the Warren shunt has been proposed as an effective operation because it decompresses the esophageal varices without disturbing portal perfusion of the liver. However, early reports of high operative mortality and technical difficulties have impeded acceptance of the procedure.
The operation was done in a series of 17 patients. All patients in whom elective variceal decompression with a patent splenic vein was required and without clinical ascites were candidates for this operation. Follow-up ranged from 2 to 48 months. Six patients had alcoholic cirrhosis, two had primary biliary cirrhosis and seven had postnecrotic cirrhosis; in two the cause of the liver disease was unknown. Five patients were categorized as Child's class A, nine as class B and three as class C. No intraoperative or early postoperative deaths owing to hemorrhage occurred. However, there was one death two weeks postoperatively from pulmonary sepsis and one death five weeks postoperatively due to antigen-positive hepatitis. Two patients died from hepatic failure six weeks and five months after operation, respectively; in the first of these, chronic active hepatitis was diagnosed at the time of operation. In one patient hemorrhage recurred and transfusion was required. Although ascites, which eventually resolved, developed in eight patients after operation, the results in 76 percent of patients have been good without new episodes of hemorrhage or encephalopathy. We conclude that the Warren shunt is a safe and effective elective operation for the treatment of patients in whom hemorrhage from esophageal varices has occurred.
PMCID: PMC1238617  PMID: 312564
16.  Clinical relevance of sarcopenia in patients with cirrhosis 
The most commonly recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, susceptibility for infections, kidney dysfunction, and hepatocellular carcinoma; however, severe muscle wasting or sarcopenia are the most common and frequently unseen complications which negatively impact survival, quality of life, and response to stressor, such as infections and surgeries. At present, D’Amico stage classification, Child-Pugh, and MELD scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of assessing the nutritional and functional status. Currently, numerous methods are available to evaluate the nutrition status of the cirrhotic patient; nevertheless, most of these techniques have limitations primarily because lack of objectivity, reproducibility, and prognosis discrimination. In this regard, an objective and reproducible technique, such as muscle mass quantification with cross-sectional imaging studies (computed tomography scan or magnetic resonance imaging) constitute an attractive index of nutritional status in cirrhosis. Sarcopenia is part of the frailty complex present in cirrhotic patients, resulting from cumulative declines across multiple physiologic systems and characterized by impaired functional capacity, decreased reserve, resistance to stressors, and predisposition to poor outcomes. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis. Also, we analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in patients with cirrhosis and their impact after liver transplantation. Finally, we discuss existing and potential novel therapeutic approaches for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in an effort to reduced morbidity related and improved survival in cirrhosis.
PMCID: PMC4081677  PMID: 25009378
Cirrhosis; Sarcopenia; Malnutrition; Prognosis; Mortality; Body composition; Lumbar skeletal muscle index; Liver transplantation
17.  Fibreoptic endoscopy and the use of the Sengstaken tube in acute gastrointestinal haemorrhage in patients with portal hypertension and varices. 
Gut  1976;17(4):258-263.
The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.
PMCID: PMC1411108  PMID: 773787
18.  Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications 
World Journal of Gastroenterology : WJG  2014;20(45):16996-17010.
Portal hypertension (PH) plays an important role in the natural history of cirrhosis, and is associated with several clinical consequences. The introduction of transjugular intrahepatic portosystemic shunts (TIPS) in the 1980s has been regarded as a major technical advance in the management of the PH-related complications. At present, polytetrafluoroethylene-covered stents are the preferred option over traditional bare metal stents. TIPS is currently indicated as a salvage therapy in patients with bleeding esophageal varices who fail standard treatment. Recently, applying TIPS early (within 72 h after admission) has been shown to be an effective and life-saving treatment in those with high-risk variceal bleeding. In addition, TIPS is recommended as the second-line treatment for secondary prophylaxis. For bleeding gastric varices, applying TIPS was able to achieve hemostasis in more than 90% of patients. More trials are needed to clarify the efficacy of TIPS compared with other treatment modalities, including cyanoacrylate injection and balloon retrograde transvenous obliteration of gastric varices. TIPS should also be considered in bleeding ectopic varices and refractory portal hypertensive gastropathy. In patients with refractory ascites, there is growing evidence that TIPS not only results in better control of ascites, but also improves long-term survival in appropriately selected candidates. In addition, TIPS is a promising treatment for refractory hepatic hydrothorax. However, the role of TIPS in the treatment of hepatorenal and hepatopulmonary syndrome is not well defined. The advantage of TIPS is offset by a risk of developing hepatic encephalopathy, the most relevant post-procedural complication. Emerging data are addressing the determination the optimal time and patient selection for TIPS placement aiming at improving long-term treatment outcome. This review is aimed at summarizing the published data regarding the application of TIPS in the management of complications related to PH.
PMCID: PMC4258568  PMID: 25493012
Transjugular intrahepatic portosystemic shunts; Portal hypertension; Cirrhosis; Varices; Ascites
19.  Study of liver cirrhosis over ten consecutive years in Southern China 
World Journal of Gastroenterology : WJG  2014;20(37):13546-13555.
AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China.
METHODS: In this retrospective, cross-sectional study, we identified cases of liver cirrhosis admitted between January 2001 to December 2010 and reviewed the medical records. Patient demographics, etiologies and complications were collected, and etiological changes were illustrated by consecutive years and within two time periods (2001-2005 and 2006-2010). All results were expressed as the mean ± SD or as a percentage. The χ2 test or Student’s t-test was used to analyze the differences in age, gender, and etiological distribution, and one-way analysis of variance was applied to estimate the trends in etiological changes. We analyzed the relationship between the etiologies and complications using unconditioned logistic regression, and the risk of upper gastrointestinal bleeding (UGIB) and hepatocellular carcinoma (HCC) in the major etiological groups was evaluated as ORs. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 17.0 software.
RESULTS: In this study, we identified 6719 (83.16%) male patients and 1361 (16.84%) female patients. The average age of all of the patients was 50.5 years at the time of diagnosis. The distribution of etiological agents was as follows: viral hepatitis, 80.62% [hepatitis B virus (HBV) 77.22%, hepatitis C virus (HCV) 2.80%, (HBV + HCV) 0.58%]; alcohol, 5.68%; mixed etiology, 4.95%; cryptogenic, 2.93%; and autoimmune hepatitis, 2.03%; whereas the other included etiologies accounted for less than 4% of the total. Infantile hepatitis syndrome LC patients were the youngest (2.5 years of age), followed by the metabolic LC group (27.2 years of age). Viral hepatitis, alcohol, and mixed etiology were more prevalent in the male group, whereas autoimmune diseases, cryptogenic cirrhosis, and metabolic diseases were more prevalent in the female group. When comparing the etiological distribution in 2001-2005 with that in 2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60.
CONCLUSION: The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC.
PMCID: PMC4188906  PMID: 25309085
Liver cirrhosis; Epidemiology; Etiology; Complication; Hepatocellular carcinoma; Southern China
20.  What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis? 
BMC Gastroenterology  2009;9:89.
Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications.
Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography.
The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66).
Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence.
PMCID: PMC2785828  PMID: 19930687
21.  The refit model for end-stage liver disease-Na is not a better predictor of mortality than the refit model for end-stage liver disease in patients with cirrhosis and ascites 
The modification of the Model for End-Stage Liver Disease (MELD) scoring system (Refit MELD) and the modification of MELD-Na (Refit MELDNa), which optimized the MELD coefficients, were published in 2011. We aimed to validate the superiority of the Refit MELDNa over the Refit MELD for the prediction of 3-month mortality in Korean patients with cirrhosis and ascites.
We reviewed the medical records of patients admitted with hepatic cirrhosis and ascites to the Konkuk University Hospital between January 2006 and December 2011. The Refit MELD and Refit MELDNa were compared using the predictive value of the 3-month mortality, as assessed by the Child-Pugh score.
In total, 530 patients were enrolled, 87 of whom died within 3 months. Alcohol was the most common etiology of their cirrhosis (n=271, 51.1%), and the most common cause of death was variceal bleeding (n=20, 23%). The areas under the receiver operating curve (AUROCs) for the Child-Pugh, Refit MELD, and Refit MELDNa scores were 0.754, 0.791, and 0.764 respectively; the corresponding values when the analysis was performed only in patients with persistent ascites (n=115) were 0.725, 0.804, and 0.796, respectively. The significant difference found among the Child-Pugh, Refit MELD, and Refit MELDNa scores was between the Child-Pugh score and Refit MELD in patients with persistent ascites (P=0.039).
Refit MELD and Refit MELDNa exhibited good predictability for 3-month mortality in patients with cirrhosis and ascites. However, Refit MELDNa was not found to be a better predictor than Refit MELD, despite the known relationship between hyponatremia and mortality in cirrhotic patients with ascites.
PMCID: PMC3992329  PMID: 24757658
Stage Liver Disease; Liver Cirrhosis; Ascites; Mortality; Hyponatremia
22.  Recurrent thrombotic occlusion of a transjugular intrahepatic portosystemic stent-shunt due to activated protein C resistance 
The transjugular intrahepatic portosystemic stent-shunt (TIPS) has successfully been used in the management of refractory variceal bleeding and ascites in patients with portal hypertension. Major drawbacks are the induction of hepatic encephalopathy and shunt dysfunction. We present a 59-year-old woman with alcoholic liver cirrhosis who received a TIPS because of recurrent bleeding from esophageal varices. Stent occlusion occurred 4 mo after placement of the TIPS. Laboratory testing revealed resistance to activated protein C (APC). Combination therapy with low-dose enoxaparin and clopidogrel could not prevent her recurrent stent occlusion. Finally, therapy with high-dose enoxaparin was sufficient to prevent further shunt complications up to now (follow-up period of 1 year). In conclusion, early occlusion of a TIPS warrants testing for thrombophilia. If risk factors are confirmed, anticoagulation should be intensified. There are currently no evidence-based recommendations regarding the best available anticoagulant therapy and surveillance protocol for patients with TIPS.
PMCID: PMC4321932  PMID: 16124068
Transjugular intrahepatic portosystemic stent-shunt; Resistance to activated protein C; Factor V-Leiden; Thrombophilia; Thrombosis
23.  What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels 
BMJ Open  2012;2(3):e000957.
To estimate the impact of achieving alternative average population alcohol consumption levels on chronic disease mortality in England.
A macro-simulation model was built to simultaneously estimate the number of deaths from coronary heart disease, stroke, hypertensive disease, diabetes, liver cirrhosis, epilepsy and five cancers that would be averted or delayed annually as a result of changes in alcohol consumption among English adults. Counterfactual scenarios assessed the impact on alcohol-related mortalities of changing (1) the median alcohol consumption of drinkers and (2) the percentage of non-drinkers.
Data sources
Risk relationships were drawn from published meta-analyses. Age- and sex-specific distributions of alcohol consumption (grams per day) for the English population in 2006 were drawn from the General Household Survey 2006, and age-, sex- and cause-specific mortality data for 2006 were provided by the Office for National Statistics.
The optimum median consumption level for drinkers in the model was 5 g/day (about half a unit), which would avert or delay 4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from cancers and liver disease would be delayed or averted (∼2800 for each), while there was a small increase in cardiovascular mortality. The model showed no benefit in terms of reduced mortality when the proportion of non-drinkers in the population was increased.
Current government recommendations for alcohol consumption are well above the level likely to minimise chronic disease. Public health targets should aim for a reduction in population alcohol consumption in order to reduce chronic disease mortality.
Article summary
Article focus
Alcohol consumption is a risk factor for many chronic diseases, while providing modest protection from others. Assessments of the impact of alcohol on individual chronic diseases can therefore result in contradictory advice about the level of alcohol consumption that is optimal for health.
The UK Government currently recommends that men should consume no more than three to four units per day (24–32 g/day of pure alcohol) and women should drink no more than two to three units per day (16–24 g/day). However the net impact of this level of consumption on chronic disease mortality is unclear.
The aim of this study was to estimate the impact of achieving alternative population alcohol consumption levels on chronic disease mortality in England.
Key messages
Results suggest that the optimum population level of alcohol consumption for minimising chronic disease mortality in England is just 5 g (approximately half a unit) per day.
Current recommendations for alcohol consumption are well above this level and may not be compatible with optimum protection of public health. Substantial reductions in recommendations and in population alcohol consumption levels would be needed to minimise the chronic disease burden associated with alcohol consumption in England.
Community beliefs in the protective role of alcohol in cardiovascular disease are widespread; however, our modelling shows that when multiple conditions are considered simultaneously, the levels of alcohol that would actually be likely to be associated with reduced risk of chronic disease are much lower than is generally accepted or recommended by government.
Strengths and limitations of this study
The study used a detailed modelling approach to synthesise the best available evidence from meta-analysis of prospective cohort studies and provide for the first time an estimate of the level of alcohol associated with theoretical minimum risk of a range of chronic diseases, considering both harmful and protective effects simultaneously.
The model is dependent on the meta-analyses selected to define the parameters. Results may vary significantly in other contexts with varying levels of disease, alcohol consumption and other risk factors. Furthermore, results depend on the quality of the available epidemiological evidence, which remains contested in some areas.
The approach used also relies on chronic (average) consumption of alcohol and is not able to take account of to take account of patterns of drinking (eg, binge drinking). Furthermore, the results are based on the assumption of a steady-state relationship between alcohol consumption patterns and RR of disease and cannot estimate the time required between changes in population alcohol consumption levels occurring and the achievement of changes in mortality rates.
PMCID: PMC3367150  PMID: 22649178
24.  EVS vs TIPS shunt for gastric variceal bleeding in patients with cirrhosis: A meta-analysis 
AIM: To evaluate the clinical effects of transjugular intrahepatic portosystemic shunt (TIPS) vs endoscopic variceal sclerotherapy (EVS) in the management of gastric variceal (GV) bleeding in terms of variceal rebleeding, hepatic encephalopathy (HE), and survival by meta-analysis.
METHODS: Medline, Embase, and CNKI were searched. Studies compared TIPS with EVS in treating GV bleeding were identified and included according to our predefined inclusion criteria. Data were extracted independently by two of our authors. Studies with prospective randomized design were considered to be of high quality. Hazard ratios (HRs) or odd ratios (ORs) were calculated using a fixed-effects model when there was no inter-trial heterogeneity. Oppositely, a random-effects model was employed.
RESULTS: Three studies with 220 patients who had at least one episode of GV bleeding were included in the present meta-analysis. The proportions of patients with viral cirrhosis and alcoholic cirrhosis were 39% (range 0%-78%) and 36% (range 12% to 41%), respectively. The pooled incidence of variceal rebleeding in the TIPS group was significantly lower than that in the EVS group (HR = 0.3, 0.35, 95%CI: 0.17-0.71, P = 0.004). However, the risk of the development of any degree of HE was significantly increased in the TIPS group (OR = 15.97, 95%CI: 3.61-70.68). The pooled HR of survival was 1.26 (95%CI: 0.76-2.09, P = 0.36). No inter-trial heterogeneity was observed among these analyses.
CONCLUSION: The improved effect of TIPS in the prevention of GV rebleeding is associated with an increased risk of HE. There is no survival difference between the TIPS and EVS groups. Further studies are needed to evaluate the survival benefit of TIPS in cirrhotic patients with GV bleeding.
PMCID: PMC4023329  PMID: 24868490
Gastric variceal bleeding; Transjugular intrahepatic portosystemic shunt; Endoscopic variceal sclerotherapy; Cirrhosis; Hepatic encephalopathy
25.  Assessment of risk of complications in cirrhosis using portal thallium scans 
AIM: To investigate the usefulness of a novel thallium scan shunt index for assessing portosystemic shunt-related cirrhotic complications.
METHODS: We enrolled 209 chronic hepatitis B-related cirrhosis patients. After rectal thallium instillation, radioactive isotope activity in the heart and liver was measured. The ratio of radiation uptake between the heart and the liver was calculated (the shunt index). This value indicates the degree of portosystemic circulation shunting. Blood tests, serum biochemistry tests, abdominal ultrasonography, gastroscopy and examination of clinical features such as the occurrence of varices, bleeding and hepatic encephalopathy were performed. Multivariate analysis was used to identify independent risk factors for complications. We compared the cumulative incidence rates of complications during the follow-up period.
RESULTS: The thallium scan shunt index was significantly higher in the decompensated liver cirrhosis group than in the compensated liver cirrhosis group (0.91 ± 0.39 vs 0.39 ± 0.32, P < 0.001). It was also higher in the varices group, the hepatic encephalopathy group, and the variceal bleeding group than in the control group (P < 0.001). Multivariate analysis showed that the index was an independent risk factor for predicting decompensated liver cirrhosis. When the cut-off value was 0.75, the shunt index had a sensitivity of 82.6%, a specificity of 84%, a positive predictive value of 61.5%, and a negative predictive value of 94.4% in diagnosing decompensated cirrhosis. When the shunt index was greater than 0.75, there was a significant increase in the number of decompensated events.
CONCLUSION: The thallium shunt index is a good predictor of cirrhosis-related complications.
PMCID: PMC3886013  PMID: 24415876
Liver cirrhosis; Portosystemic shunt; Decompensation

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