Adrenocortical dysfunction in liver disease: A systematic review.
Hepatology. 201…

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Albumin infusion in patients undergoing large-volume paracentesis: A meta-analysis of ran…

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Intensive care of the patient with cirrhosis.
Hepatology. 2011 Aug 24;
Authors: Olson JC, Wendon JA, Kramer DJ, Arroyo V, Jalan R, Garcia-Tsao G, Kamath PS
Abstract
Acute deterioration of patients with cirrhosi…

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Idiopathic non-cirrhotic portal hypertension.
Hepatology. 2011 May 13;
Authors: Jnl S, Jc GP, Dc V, Hla J
Idiopathic non-cirrhotic portal hypertension (INCPH) is characterized by an increased portal venous pressure gra…

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Hepatic encephalopathy: A central neuroinflammatory disorder?
Hepatology. 2011 Apr;53(4):1372-6
Authors: Butterworth RF
Encephalopathy and brain edema are serious central nervous system complications of liver failure. …

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Drug-induced cholestasis.
Hepatology. 2011 Apr;53(4):1377-87
Authors: Padda MS, Sanchez M, Akhtar AJ, Boyer JL
Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new…

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Autoimmune acute liver failure: Proposed clinical and histological criteria.

Hepatology. 2011 Feb;53(2):517-526

Authors: Stravitz RT, Lefkowitch JH, Fontana RJ, Gershwin ME, Leung PS, Sterling RK, Manns MP, Norman GL, Lee WM,

Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoi mmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell-enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti-smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Conclusion: Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. (HEPATOLOGY 2011;53:517-526).

PMID: 21274872 [PubMed - as supplied by publisher]

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Noninvasive assessment of portal hypertension in patients with cirrhosis.

Hepatology. 2011 Feb;53(2):683-694

Authors: Thabut D, Moreau R, Lebrec D

Severe portal hypertension is responsible for complications and death. Although measurement of the hepatic venous pressure gradient is the most accurate method for evaluating the presence and severity of portal hypertension, this technique is considered invasive and is not routinely performed in all centers. Several noninvasive techniques have been proposed to measure portal hypertension. Certain methods evaluate elements related to the pathogenesis of portal hypertension through the measurement of hyperkinetic syndrome, for example, or they investigate the development of hepatic fibrosis through the measurement of increased intrahepatic vascular resistance. Other methods evaluate the clinical consequences of portal hypertension, such as the presence of esophageal varices or the development of portosystemic shunts. Methods evaluating increased hepatic vascular resistance are fairly accurate and mainly involve the detection of hepatic fibrosis by serum markers and transient elastography. The radiological assessment of hyperkinetic syndrome probably has value but is still under investigation. The assessment of severe portal hypertension by the presence of varices may be performed with simple tools such as biological assays, computed tomography, and esophageal capsules. More sophisticated procedures seem promising but are still under development. Screening tools for large populations must be simple, whereas more complicated procedures could help in the follow-up of already diagnosed patients. Although most of these noninvasive methods effectively identify severe portal hypertension, methods for diagnosing moderate portal hypertension need to be developed; this shows that further investigation is needed in this field. (HEPATOLOGY 2011;53:683-694).

PMID: 21274889 [PubMed - as supplied by publisher]

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Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure.

Hepatology. 2010 Nov 4;

Authors: Khandelwal N, James LP, Sanders C, Larson AM, Lee WM,

Despite extensive investigations, the cause of liver injury in 14% of patients with acute liver failure remains unknown (indeterminate). In a pilot study using a novel assay, highly specific acetaminophen-cysteine adducts were detected in 7 of 36 indeterminate patients (19%). To extend these observations, sera from 110 subjects enrolled in the Acute Liver Failure Study Group registry with indeterminate acute liver failure were analyzed with a similar but more efficient and sensitive adduct assay. As positive controls, another 199 patients with known or presumed acetaminophen-induced liver failure were assessed for the presence and quantity of adducts. Clinical, laboratory, and outcome data were compared for the two groups. On the basis of previous data for known therapeutic exposures and acetaminophen overdoses, an adduct concentration ?1.0 nmol/mL of serum indicated a definite acetaminophen overdose. Among the 110 indeterminate cases, 18% had assay values ?1.0 with a median level of 9.2 nmol/mL; 94.5% of the positive controls (known acetaminophen cases) had values ?1.0 nmol/mL. Regardless of the initial diagnosis, subjects with elevated adduct levels demonstrated the clinical profile and hyperacute biochemical injury pattern associated with acetaminophen overdose: a predominance of female gender, very high aminotransferase levels, and low bilirubin levels. Conclusion: These data confirm and extend previous observations regarding the high (18%) prevalence of unrecognized or uncertain acetaminophen toxicity among subjects with indeterminate acute liver failure. N-Acetylcysteine use was limited in this group, presumably because of the lack of a specific diagnosis of acetaminophen toxicity. (HEPATOLOGY 2011;.).

PMID: 21225650 [PubMed - as supplied by publisher]

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Theophylline improves steroid sensitivity in acute alcoholic hepatitis.

Hepatology. 2010 Jul;52(1):126-31

Authors: Kendrick SF, Henderson E, Palmer J, Jones DE, Day CP

Corticosteroid therapy has shown some benefit in severe acute alcoholic hepatitis (AAH); however, this is limited by uncertainty in patient selection and variable clinical response. Theophylline has been shown to ameliorate impaired steroid sensitivity in chronic obstructive pulmonary disease by facilitating corticosteroid-induced silencing of proinflammatory genes. We aimed to explore the mechanistic basis of the variable response to corticosteroid therapy seen in patients with AAH and to address the extent to which theophylline can improve this response. The ability of dexamethasone to inhibit phytohemagglutinin-induced lymphocyte proliferation was assessed by (3)H-thymidine incorporation in 12 severe AAH patients and age-matched and sex-matched controls. Steroid sensitivity was measured in terms of I(max), the maximum inhibition of proliferation. The effect of 10(-5) M theophylline and, in survivors, change in I(max) during recovery were observed. Lymphocyte steroid sensitivity was found to be significantly reduced in AAH compared with controls (I(max) 67[+/-4.5]% versus 95[+/-2.3]%, P = 0.0002) and correlated with clinical markers of steroid responsiveness. In survivors, I(max) increased in recovery. Theophylline 10(-5) M significantly increased lymphocyte steroid sensitivity (I(max) 86[+/-6.6]% versus 67[+/-5.0]%, P = 0.027). CONCLUSION: Acute alcoholic hepatitis is associated with significant lymphocyte steroid insensitivity, which improves in recovery and can be ameliorated ex vivo by theophylline. This offers potential to rationalize corticosteroid prescribing in AAH and, furthermore, justifies investigation of this novel role for an existing pharmacological agent in this common and frequently fatal condition.

PMID: 20578267 [PubMed - indexed for MEDLINE]

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Controlled trial of ligation plus nadolol versus nadolol alone for the prevention of first variceal bleeding.

Hepatology. 2010 Jul;52(1):230-7

Authors: Lo GH, Chen WC, Wang HM, Lee CC

Both nadolol and ligation have proved to be effective in the prophylaxis of first variceal bleeding. This study was conducted to evaluate the effects and safety of combining nadolol with ligation. Cirrhotic patients with high-risk esophageal varices but without a bleeding history were considered for enrolment. Eligible patients were randomized to receive band ligation plus nadolol (Combined group, 70 patients) or nadolol alone (Nadolol group, 70 patients). In the Combined group multiligators were applied. Patients received regular ligation treatment at an interval of 4 weeks until variceal obliteration. Nadolol was administered at a dose to reduce 25% of the pulse rate in both the Combined group and the Nadolol group. Both groups were comparable in baseline data. In the Combined group 50 patients (71%) achieved variceal obliteration. The mean dose of nadolol was 52 +/- 16 mg in the Combined group and 56 +/- 19 mg in the Nadolol group. During a median follow-up of 26 months, 18 patients (26%) in the Combined group and 13 patients (18%) in the Nadolol group experienced upper gastrointestinal bleeding (P = NS). Esophageal variceal bleeding occurred in 10 patients (14%) in the Combined group and nine patients (13%) in the Nadolol group (P = NS). Adverse events were noted in 48 patients (68%) in the Combined group and 28 patients (40%) in the Nadolol group (P = 0.06). Sixteen patients in each group died. CONCLUSION: The addition of ligation to nadolol may increase adverse events and did not enhance effectiveness in the prophylaxis of first variceal bleeding.

PMID: 20578138 [PubMed - indexed for MEDLINE]

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Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

Hepatology. 2010 Jan;51(1):210-8

Authors: Plessier A, Darwish-Murad S, Hernandez-Guerra M, Consigny Y, Fabris F, Trebicka J, Heller J, Morard I, Lasser L, Langlet P, Denninger MH, Vidaud D, Condat B, Hadengue A, Primignani M, Garcia-Pagan JC, Janssen HL, Valla D,

Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. CONCLUSION: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present.

PMID: 19821530 [PubMed - indexed for MEDLINE]

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Management of adult patients with ascites due to cirrhosis: an update.

Hepatology. 2009 Jun;49(6):2087-107

Authors: Runyon BA,

PMID: 19475696 [PubMed - indexed for MEDLINE]

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Evaluation of the patient with hepatitis B.

Hepatology. 2009 May;49(5 Suppl):S22-7

Authors: Rotman Y, Brown TA, Hoofnagle JH

The initial evaluation of a patient with hepatitis B virus infection should attempt to assess the disease activity and stage in the context of the known natural history of this infection and to properly assess the needs for treatment and surveillance. In addition to a medical history and focused physical examination, the initial evaluation usually requires serological, biochemical, and virological tests to confirm the diagnosis as well as an imaging study to establish a baseline for future monitoring. A liver biopsy is generally not needed but can provide useful information on prognosis, need for surveillance for hepatocellular carcinoma (HCC), and whether to recommend therapy. Follow-up monitoring is aimed at determining disease progression, development of complications, and reassessing the need for treatment. Monitoring frequency should be determined based on the activity and stage of disease. Initiation of screening for HCC should be based on age, race, sex, family history, and stage and duration of disease. The current recommended method of screening and surveillance for HCC is by ultrasonography and alpha-fetoprotein measurements every 6-12 months. Prospective studies are needed to evaluate the role of longitudinal application of noninvasive assays of fibrosis, such as serum fibrosis markers and transient elastography. Better biomarkers and imaging modalities are needed for early detection of HCC. Finally, studies are needed to better refine the indications and to balance the risks and benefits of antiviral therapy.

PMID: 19399815 [PubMed - indexed for MEDLINE]

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Predicting in-hospital mortality in patients with cirrhosis: results differ across risk adjustment methods.

Hepatology. 2009 Feb;49(2):568-77

Authors: Myers RP, Quan H, Hubbard JN, Shaheen AA, Kaplan GG

Risk-adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in-hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005. The performance of four common risk adjustment methods (the Charlson/Deyo and Elixhauser comorbidity algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups [APR-DRGs]) for predicting in-hospital mortality was determined using the c-statistic. Subgroup analyses were conducted according to a primary versus secondary diagnosis of cirrhosis and in homogeneous patient subgroups (hepatic encephalopathy, hepatocellular carcinoma, congestive heart failure, pneumonia, hip fracture, and cholelithiasis). Patients were also ranked according to the probability of death as predicted by each method, and rankings were compared across methods. Predicted mortality according to the risk adjustment methods agreed for only 55%-67% of patients. Similarly, performance of the methods for predicting in-hospital mortality varied significantly. Overall, the c-statistics (95% confidence interval) for the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and APR-DRGs were 0.683 (0.680-0.687), 0.749 (0.746-0.752), 0.832 (0.829-0.834), and 0.875 (0.873-0.878), respectively. Results were robust across diagnostic subgroups, but performance was lower in patients with a primary versus secondary diagnosis of cirrhosis. Conclusion: Mortality analyses in patients with cirrhosis require sensitivity to the method of risk adjustment. Because different methods often produce divergent severity rankings, analyses of provider-specific outcomes may be biased depending on the method used.

PMID: 19085957 [PubMed - indexed for MEDLINE]

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