Cirrhosis Blog

Garcia-Tsao G.
Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA. guadalupe.garcia-tsao@yale.edu

Gastroesophageal varices are a direct consequence of portal hypertension. Nonselective beta-adrenergic blockers decrease portal pressure and are effective in preventing variceal hemorrhage. However, a large multicenter placebo-controlled trial demonstrates that nonselective beta-adrenergic blockers are not effective in preventing the development of varices and are associated with a significant rate of adverse events. This therapy is, therefore, not recommended in compensated cirrhotic patients without varices at large. In this very compensated group of patients with cirrhosis (stage 1, ie, without varices and without ascites or encephalopathy) the predictive value (both for the development of varices and for the development of clinical decompensation) of a baseline hepatic venous pressure gradient greater than 10 mm Hg is confirmed, supporting this threshold level as one that defines a clinically significant portal hypertension. Importantly, reductions in hepatic venous pressure gradient >10% are associated with a significant reduction in the development of varices, a therapeutic goal that could be achieved through the use of beta-blockers or other drugs being developed for the treatment of portal hypertension.

Rishe E, Azarm A, Bergasa NV.
Department of Medicine, Beth Israel Medical Center.

The perception of itch in primary biliary cirrhosis (PBC) is not characterized. Patients with primary biliary cirrhosis who were members of the PBCers Organization were invited to participate in an on-line survey addressing certain characteristics of their itch. Patients used their own words in the questions that asked for descriptions. A total of 238 subjects responded to the survey; of these, 231 were women, and 165 (69%) reported itch. One hundred and twenty-four patients from the 165 (75%) reported that itch preceded the diagnosis of primary biliary cirrhosis. A total of 58 from 164 (35%) respondents described their itch as “bugs crawling”. Fifty-seven of 88 (64.7%) subjects reported that something cool relieved their itch, and 69 of 112 (61.6%) reported that heat worsened it. One hundred and seven of 164 (65.2%) respondents reported that the itch was worse at night. The most commonly prescribed medications were antihistamines and cholestyramine, and the most common type of medication reported as being associated with relief was antihistamine drugs. There was no systematic approach to the evaluation and treatment of itch in patients with primary biliary cirrhosis. Education on the subject of itch in primary biliary cirrhosis is warranted.

Kumagi T, Heathcote JE.

ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million population and prevalence between 6.7 and 940 cases per million population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren’s syndrome, scleroderma, Raynaud’s phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have a potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciati
on for novel treatment in PBC.

Møller S, Henriksen JH.
Department of Clinical Physiology, 239, Hvidovre Hospital, DK-2650 Copenhagen, Denmark. soeren.moeller@hvh.regionh.dk

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis without adequate plasma volume expansion, transjugular intrahepatic portosystemic shunt (TIPS) insertion, peritoneovenous shunting and surgery. Cardiac failure is an important cause of mortality after liver transplantation, but improved liver function has also been shown to reverse the cardiac abnormalities. No specific treatment can be recommended, and cardiac failure should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and oxygen therapy when necessary. Special care should be taken with the use of ACE inhibitors and angiotensin antagonists in these patients. The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.

Castellares C, Barreiro P, Martín-Carbonero L, Labarga P, Vispo ME, Casado R, Galindo L, García-Gascó P, García-Samaniego J, Soriano V.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan((R))). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan((R)) between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/muL respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis.

Gundling F, Gülberg V, Schepp W, Mann J.
Klinik für Gastroenterologie, Hepatologie und Gastroenterologische Onkologie, Klinikum Bogenhausen, Städtisches Klinikum München GmbH, München. Felix.Gundling@gmx.de

A lot of patients suffering from liver cirrhosis show a decreased renal perfusion and glomerular filtration rate. An impaired renal function is the result of complex e.g. hemodynamic disturbances, resulting of the chronic liver disease. This explains its disposition to renal dysfunction and the higher incidence of acute renal failure in liver cirrhosis. In the case of renal failure hepatorenal syndrome, apart from prerenal, renal and postrenal causes, should be included in the differential diagnosis especially when signs of portal hypertension are apparent regarding its high mortalityand fatal prognosis requiring an immediate therapeutically approach. Special attention must be due to preventive strategies to avoid renal deterioration. This includes simple steps e.g. a careful election of medication but also an adequate therapy of infection-associated complications in patients with liver cirrhosis.

Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A, Soriano G, Terra C, Fábrega E, Arroyo V, Rodés J, Ginès P; TAHRS Investigators.
Liver Unit, Hospital Clínic, University of Barcelona School of Medicine, Institut d’Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Centro de Investigacíon Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.

BACKGROUND & AIMS: Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS: Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS: Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS: As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

O’Leary JG, Lepe R, Davis GL.
Hepatology, Department of Medicine, Baylor University Medical Center, Dallas, Texas 75246, USA.

Patients should be considered for liver transplantation if they have evidence of fulminant hepatic failure, a life-threatening systemic complication of liver disease, or a liver-based metabolic defect or, more commonly, cirrhosis with complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, hepatorenal syndrome, or bleeding caused by portal hypertension. While the complications of cirrhosis can often be managed relatively effectively, they indicate a change in the natural history of the disease that should lead to consideration of liver transplantation. Referral to a liver transplant center is followed by a detailed medical evaluation to ensure that transplantation is technically feasible, medically appropriate, and in the best interest of both the patient and society. Patients approved for transplantation are placed on a national transplant list, although donor organs are allocated locally and regionally. Since 2002, priority for transplantation has been determined by the Model of End-Stage Liver Disease (MELD) score, which provides donor organs to listed patients with the highest estimated short-term mortality.

Veldt BJ, Chen W, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, de Knegt RJ, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL.
Erasmus MC University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands.

Recent studies suggest that diabetes mellitus increases the risk of developing hepatocellular carcinoma (HCC). The aim of this study is to quantify the risk of HCC among patients with both diabetes mellitus and hepatitis C in a large cohort of patients with chronic hepatitis C and advanced fibrosis. We included 541 patients of whom 85 (16%) had diabetes mellitus. The median age at inclusion was 50 years. The prevalence of diabetes mellitus was 10.5% for patients with Ishak fibrosis score 4, 12.5% for Ishak score 5, and 19.1% for Ishak score 6. Multiple logistic regression analysis showed an increased risk of diabetes mellitus for patients with an elevated body mass index (BMI) (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.00-1.11; P = 0.060) and a decreased risk of diabetes mellitus for patients with higher serum albumin levels (OR, 0.81; 95% CI, 0.63-1.04; P = 0.095). During a median follow-up of 4.0 years (interquartile range, 2.0-6.7), 11 patients (13%) with diabetes mellitus versus 27 patients (5.9%) without diabetes mellitus developed HCC, the 5-year occurrence of HCC being 11.4% (95% CI, 3.0-19.8) and 5.0% (95% CI, 2.2-7.8), respectively (P = 0.013). Multivariate Cox regression analysis of patients with Ishak 6 cirrhosis showed that diabetes mellitus was independently associated with the development of HCC (hazard ratio, 3.28; 95% CI, 1.35-7.97; P = 0.009). CONCLUSION: For patients with chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk of developing HCC.

Singh V, Dheerendra PC, Singh B, Nain CK, Chawla D, Sharma N, Bhalla A, Mahi SK.
Department of Hepatology, Postgraduate Insitiute of Medical Education and Research, Chandigarh, India.

OBJECTIVES: Intravenous albumin has been used to prevent paracentesis-induced circulatory dysfunction (PICD) in cirrhotics; however, its use is costly and controversial. Splanchnic arterial vasodilatation is primarily responsible for PICD. There are no reports of use of midodrine in the prevention of PICD. In this pilot study, we evaluated midodrine and albumin in the prevention of PICD. METHODS: Forty patients with cirrhosis underwent therapeutic paracentesis with midodrine or albumin in a randomized controlled trial at a tertiary center. Effective arterial blood volume was assessed by plasma renin activity. RESULTS: Plasma renin activity at baseline and at 6 days after paracentesis did not differ in the two groups (43.18 +/- 10.73 to 45.90 +/- 8.59 ng/mL/h, P= 0.273 in the albumin group and 44.44 +/- 8.44 to 41.39 +/- 10.21 ng/mL/h, P= 0.115 in the midodrine group). Two patients had an increase in plasma renin activity of more than 50% from baseline in the albumin group, and none in the midodrine group. A significant increase in 24-h urine volume and urine sodium excretion was noted in the midodrine group. Midodrine therapy was cheaper than albumin therapy. CONCLUSIONS: The study suggests that midodrine may be as effective as albumin in preventing PICD in cirrhotics, but at a fraction of the cost, and can be administered orally. Midodrine also resulted in an increase in 24-h urine volume and sodium excretion.