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Journal of Hepatology 02/2013; · 9.26 Impact Factor
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ABSTRACT: Significant strides have been made in the last few years in advancing our knowledge of the natural history of cirrhosis. These include (1) a better understanding of prognosis in compensated and decompensated cirrhosis, (2) improved estimates of the natural course of variceal bleeding in patients receiving standard of care therapy, (3) recognition of renal failure and infection as important determinants of mortality in the clinic course, (4) realization of the importance of hepatic venous pressure gradient as a marker of prognosis, progression, and treatment response, and (5) evolution of noninvasive studies of liver stiffness as potential predictors of decompensation. Further studies identifying cirrhotics at highest risk of transitioning from a compensated state to a decompensated state will be important in order to alter the natural history of cirrhosis.
Current Gastroenterology Reports 02/2013; 15(2):308.
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ABSTRACT: Acute-on-chronic liver failure (ACLF) is an increasingly recognised entity encompassing an acute deterioration of liver function in patients with cirrhosis, which is usually associated with a precipitating event and results in the failure of one or more organs and high short term mortality. Prospective data to define this is lacking but there is a large body of circumstantial evidence suggesting that this condition is a distinct clinical entity. From the pathophysiologic perspective, altered host response to injury and infection play important roles in its development. This review focuses upon the current understanding of this syndrome from the clinical, prognostic and pathophysiologic perspectives and indicates potential biomarkers and therapeutic targets for intervention.
Journal of Hepatology 06/2012; · 9.26 Impact Factor
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ABSTRACT: In a population-based study, we examined recurrence rates of acute pancreatitis (AP) after cholecystectomy performed to prevent recurrences of AP.
We abstracted data from medical records of all Olmsted county residents who underwent cholecystectomy at Mayo Clinic for the management of presumed gallstone or idiopathic AP between 1990 and 2005 (n = 239). Based on (i) significantly elevated liver enzymes (≥threefold increase of alanine aminotransferase or aspartate aminotransferase) on day 1 and (ii) the presence of gallstones/sludge in the gall bladder, we categorized patients into 4 groups: A (i + ii), B (i but not ii), C (ii but not i), and D (neither i nor ii). Recurrence rates of AP after cholecystectomy were determined in all groups.
The median follow-up after cholecystectomy was 99 months (range, 8-220). AP recurred in 13 of 142 patients (9%) in group A, 1 of 17 patients (6%) in group B, 13 of 57 patients (23%) in group C, and 14 of 23 patients (61%) in group D (P < .0001 D vs. all other groups and P = .001 C vs. groups A and B). No difference was seen in recurrence rates in groups A vs. B (P = 1.0). Recurrences were more frequent in patients with normal liver enzymes (A + B vs. C + D; P = .000003) and in patients without sonographic evidence of gallstones/sludge (A + C vs. B + D; P = .0008).
When AP is associated with significantly elevated liver enzymes on day 1, recurrence rates after cholecystectomy are low (9%). However, postcholecystectomy recurrence rates of AP are high in those without such laboratory abnormalities (34%), especially in those without gall bladder stones/sludge (61%) on abdominal ultrasonography. Our results raise doubts about the efficacy of cholecystectomy to prevent recurrent AP in patients with the absence of either a significant elevation of liver tests on day 1 of AP or gallstones and/or sludge in the gall bladder on initial ultrasound examination.
Surgery 02/2012; 151(2):199-205. · 3.10 Impact Factor
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ABSTRACT: Acute-on-chronic liver failure (ACLF) is a clinical entity that is well recognized by those who care for patients with cirrhosis, however in spite of this widespread recognition, there remains little consensus with regard to definition and clinical features. While many similarities exist between ACLF and decompensated cirrhosis, there are also key differences, the implications of which are far reaching for both clinicians and patients alike. Among these differences are the possibility of a reversible component, the presence of a defined insult, prognosis, and outcomes associated with ACLF (see Fig. 1). However, for ACLF to have meaningful clinical implications, it first must be defined. If ACLF can be clearly defined and more easily recognized, then clinicians may be better able to prevent, treat, prognosticate, and counsel such patients.
Current Gastroenterology Reports 11/2011; 14(1):63-6.
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ABSTRACT: Acute deterioration of patients with cirrhosis manifests as multiple organ failure requiring admission to an intensive care unit. Precipitating events may be viral hepatitis, typically in Asia, and drug or alcoholic hepatitis and variceal hemorrhage in the West. Patients with cirrhosis in the intensive care unit have a high mortality, and each admission is associated with a mean charge of US $116,200. Prognosis is determined by the number of organs failing (sequential organ failure assessment [SOFA] score), the presence of infection, and the degree of liver dysfunction (Child-Turcotte-Pugh or Model for End-Stage Liver Disease scores). The most common organ failing is the kidney; sepsis is associated with further deterioration in liver function by compromise of the microcirculation. Care of these critically ill patients with impending multiple organ failure requires a team approach with expertise in both hepatology and critical care. Treatment is aimed at preventing further deterioration in liver function, reversing precipitating factors, and supporting failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. Treatment is futile in some patients, but it is difficult to identify these patients a priori. Artificial and bioartificial liver support systems have thus far not demonstrated significant survival benefit in these patients.
Hepatology 08/2011; 54(5):1864-72. · 11.66 Impact Factor
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ABSTRACT: We documented the frequency of large spontaneous portosystemic shunts in patients with moderate or severe portopulmonary hypertension (POPH) and determined the association between large shunts and response to treatment.
We performed a retrospective case-control study of data from patients with mild (mean pulmonary artery pressure [MPAP], 25-35 mm Hg; n = 18), moderate (MPAP, 35-50 mm Hg; n = 45), and severe POPH (MPAP, >50 mm Hg; n = 16). Data were compared with those from controls (normal echocardiography with estimated right ventricular systolic pressure, <35 mm Hg; n = 122). Spontaneous portosystemic shunts greater than 10 mm in diameter, identified by computed tomography or magnetic resonance, were classified as large. Response to treatment at 6 months was defined by right ventricular systolic pressure or MPAP as significant (<35 mm Hg), partial (35-50 mm Hg), or no response (>50 mm Hg).
The frequency of spontaneous shunts did not differ significantly between groups of subjects with severe (n = 14 of 16), moderate (n = 38 of 45), or mild POPH (n = 11 of 18) or normal echocardiograms (controls, n = 86 of 122) (P = .77). Large shunts were associated with severe (14 of 16) and moderate POPH (32 of 45), compared with mild POPH (6 of 18) or controls (30 of 122) (P < .01). In 13 patients with severe POPH, large shunts were associated with lack of response to treatment in 90% (8 of 9) or partial response in 50% (2 of 4). Among 27 patients with moderate POPH, large shunts were associated with no response to treatment in 13 of 19 (68%) and a partial response in 2 of 6 (33%).
Large spontaneous portosystemic shunts are associated significantly with moderate and severe POPH, and with lack of response to treatment.
Gastroenterology 06/2011; 141(5):1673-9. · 11.68 Impact Factor
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Patrick S Kamath
Hepatology 06/2011; 54(2):393-5. · 11.66 Impact Factor
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Gastroenterology 06/2011; 140(7):2137-8. · 11.68 Impact Factor
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ABSTRACT: A population of patients with previously compensated cirrhosis will develop acute deterioration resulting in multiorgan failure and high short-term mortality. Complications of cirrhosis frequently culminate in admissions to the ICU. This review advances the concept of acute-on-chronic liver failure as a distinct clinical entity.
Recently, the American Association for the Study of Liver Disease and the European Association for the Study of the Liver created a research consortium to advance the state of the science of acute-on-chronic liver failure. The goal of this consortium is aimed at improving outcomes, identification of a subset of patients with cirrhosis at high risk for deterioration, and the inciting events that lead to this deterioration. Liver transplant remains the only curative option for advanced cirrhosis; however, the limited number of available organs necessitates innovations in the care of advanced liver disease. Liver replacement therapies have not as yet demonstrated reduction in mortality, but have demonstrated improvements in other measures. Large-scale prospective studies of cirrhosis are required.
Acute-on-chronic liver failure may be a distinct clinical entity with a potential for reversibility when identified early and managed with aggressive critical care support.
Current opinion in critical care 02/2011; 17(2):165-9. · 2.67 Impact Factor
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ABSTRACT: To compare the Model for End-Stage Liver Disease (MELD) with the modified model including sodium (MELDNa) for predicting 180-day mortality in patients with alcoholic hepatitis (AH) and determine the subset in whom serum sodium may enhance 180-day mortality prediction.
We examined 26 patients with AH enrolled in a prospective trial between June 1, 2004, and June 30, 2007, at Mayo Clinic. Logistic regression analysis was done to assess the effect of MELD and MELDNa scores on 180-day mortality. The C statistic was derived to compare MELD with MELDNa in patients with and without ascites.
MELD (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.47; P = .007; C statistic, 0.81) and MELDNa (OR, 1.24; 95% CI, 1.05-1.56; P = .008; C statistic, 0.78) were significant predictors of 180-day mortality in patients with AH. A MELD score of 27.0 and a MELDNa score of 28.0 had sensitivity of 76.5% and 87.5% and specificity of 64.9% and 52.5%, respectively. In patients with AH and ascites, MELDNa (OR, 2.27; 95% CI, 1.22-36.68; P = .008; C statistic, 0.97) was a better predictor of 180-day mortality than MELD (OR, 1.37; 95% CI, 1.07-2.12; P = .006; C statistic, 0.90). A MELD score of 29.0 and a MELDNa score of 34.0 had sensitivity of 85.7% and 83.3% and specificity of 31.0% and 16.7%, respectively.
MELD and MELDNa were similar predictors of 180-day mortality; however, MELDNa was a better predictor of mortality than MELD in patients with ascites. Hyponatremia in patients with AH without ascites is not a predictor of mortality because it may have a dilutional basis secondary to excessive intake of low-osmolar alcohol.
Mayo Clinic Proceedings 01/2011; 86(1):37-42. · 5.70 Impact Factor
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Hepatology 12/2010; 52(6):2223-30. · 11.66 Impact Factor
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Hepatology 11/2010; 52(6):2223 - 2230. · 11.66 Impact Factor
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ABSTRACT: Bleeding from oesophageal varices is still a lethal complication in cirrhotic patients with portal hypertension. Approximately 5-10% of patients with cirrhosis will develop oesophageal varices per year, and about 25-30% of cirrhotic patients with oesophageal varices and without previous variceal haemorrhage will bleed from ruptured varices. To date, data on preventing the formation/growth of oesophageal varices (preprimary prophylaxis) are conflicting, with insufficient evidence to use β-blockers. There is evidence for the need for primary prophylaxis, and both β-blockers and endoscopic variceal ligation have shown the same efficacy in preventing first bleeding, but which one to prefer is still controversial. The present article reviews the established and potential therapeutic strategies for preventing the development and rupture of oesophageal varices.
Liver international: official journal of the International Association for the Study of the Liver 10/2010; 31(1):108-19. · 3.82 Impact Factor
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Liver Transplantation 09/2010; 16(9):1009-12. · 3.39 Impact Factor
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ABSTRACT: Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition.
To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis.
A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age-adjusted standardized neuropsychological factor scores were then compared for the two groups.
Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls.
The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment.
This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.
Liver international: official journal of the International Association for the Study of the Liver 07/2010; 30(6):841-9. · 3.82 Impact Factor
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ABSTRACT: Serum creatinine, a component of the model for end-stage liver disease (MELD), is an important prognostic indicator in patients with end-stage liver disease (ESLD). In addition, serum sodium has recently been recognized as an important predictor of mortality in patients with ESLD. We investigate the role of serum creatinine and sodium, and glomerular filtration rate (GFR) as determinants of survival in patients with ESLD.
A prospective database was utilized to identify all adults listed for primary liver transplantation (LTx) at the Mayo Clinic, Rochester, between 1990 and 1999. GFR was measured by iothalamate clearance.
Among 837 patients listed for LTx, 660 had complete data including measured GFR. There was a significant association between GFR and survival after adjustment for MELD, with a linear rise in the risk of death as GFR decreased between 60 and 20ml/min/1.73m(2). Multivariable models showed that GFR is superior to creatinine in predicting mortality - a model consisting of total bilirubin (hazard ratio (HR)=2.17, p<0.01), INR (HR=3.26, p<0.01) and GFR (HR=0.42, p<0.01) was superior to MELD (chi-square 65.6 vs. 59.4, c-statistic 0.792 vs. 0.780). Serum sodium did not contribute to survival prediction when accurately measured GFR data were available.
Serum concentrations of creatinine and sodium in patients with end-stage liver disease reflect a reduction in renal function, the underlying event that decreases survival.
Journal of Hepatology 02/2010; 52(4):523-8. · 9.26 Impact Factor
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ABSTRACT: The pulmonary complications of end-stage liver disease include hepatopulmonary syndrome and portopulmonary hypertension. The etio-pathogenesis of these conditions is as yet unclear. Hepatopulmonary syndrome is a gas exchange abnormality and usually manifests as hypoxemia secondary to intra-pulmonary vascular shunts. These shunts can be demonstrated by echocardiography using agitated saline injections, and quantitated by lung perfusion scans. Liver transplantation is the treatment of choice for hepatopulmonary syndrome, and there are no effective pharmacological therapies. Portopulmonary hypertension is a hemodynamic problem which manifests as fatigue and right sided cardiac failure. Several vasoactive agents have been used to lower mean pulmonary arterial pressures. Portopulmonary hypertension is a relative contraindication to liver transplantation.
Hepatology Research 10/2009; 39(10):1020-2. · 2.20 Impact Factor
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ABSTRACT: Liver stiffness is associated with portal hypertension in patients with chronic liver disease. However, the relation between spleen stiffness and clinically significant portal hypertension remains unknown. The purposes of this study were to determine the feasibility of measuring spleen stiffness with MR elastography and to prospectively test the technique in healthy volunteers and in patients with compensated liver disease.
Spleen stiffness was measured with MR elastography in 12 healthy volunteers (mean age, 37 years; range, 25-82 years) and 38 patients (mean age, 56 years; range, 36-60 years) with chronic liver disease of various causes. For patients with liver disease, laboratory findings, spleen size, presence and size of esophageal varices, and liver histologic results were recorded. Statistical analyses were performed to assess all measurements.
MR elastography of the spleen was successfully performed on all volunteers and patients. The mean spleen stiffness was significantly lower in the volunteers (mean, 3.6 +/- 0.3 kPa) than in the patients with liver fibrosis (mean, 5.6 +/- 5.0 kPa; range, 2.7-19.2 kPa; p < 0.001). In addition, a significant correlation was observed between liver stiffness and spleen stiffness for the entire cohort (r(2) = 0.75; p < 0.001). Predictors of spleen stiffness were splenomegaly, spleen volume, and platelet count. A mean spleen stiffness of 10.5 kPa or greater was identified in all patients with esophageal varices.
MR elastography of the spleen is feasible and shows promise as a quantitative method for predicting the presence of esophageal varices in patients with advanced hepatic fibrosis.
American Journal of Roentgenology 07/2009; 193(1):122-7. · 2.78 Impact Factor
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ABSTRACT: The Model for End-stage Liver Disease (MELD) has been demonstrated to be an excellent predictor of survival in patients who have end-stage liver disease. It is derived from the international normalized ratio (INR) of prothrombin time, serum creatinine, and serum total bilirubin. The major use of the MELD score is to prioritize allocation of organs for liver transplant among patients who have chronic liver disease. Virtually every study that has looked at the MELD score as a predictor of survival has demonstrated that the MELD score using the INR with international sensitivity index calibrated for patients on warfarin has a 'c' statistic of approximately 0.8, indicating excellent discrimination.
Clinics in liver disease 03/2009; 13(1):63-6.
