Maddrey Discriminant Function Score Research Articles

New prognostic model for hospitalized patients with alcoholic cirrhosis and Maddrey's discriminant function

Few studies have investigated the prognosis of patients with non-severe alcoholic hepatitis (Non-SAH). The study aimed to develop a new prognostic model for patients with especially Non-SAH. We extracted 316 hospitalized patients with alcoholic cirrhosis without severe alcoholic hepatitis, defined as Maddrey's discriminant function score lower than 32, from the retrospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort to develop a new prognostic model (training set), and validated it in 419 patients from the prospective KACLiF cohort (validation set). Prognostic factors for death and liver transplantation were analyzed to construct a prognostic model. Twenty-one and 24 patients died within 6 months in both sets, respectively. In the training set, the highest area under the curve (AUC) of conventional prognostic models was 0.765, 0.732, and 0.684 for 1-, 3-, and 6-month mortality, respectively. Refractory ascites, vasopressor use, and hyponatremia were independently associated with mortality of cirrhotic patients with Non-SAH. The new model consisted of four variables: past deterioration, neutrophil proportion > 70%, Na < 128 mmol/L, and vasopressor use. It showed the highest accuracy for short-term mortality in the training and validation sets (0.803 and 0.786; 0.797 and 0.776; and 0.789 and 0.721 for 1-, 3-, and 6-month mortality, respectively). There is a group of patients with high risk among those classified as Non-SAH. The new model will help stratifying cirrhotic patients with Non-SAH more accurately in terms of prognosis. The patients with high Non-SAH score need to monitor closely and might be considered for preemptive liver transplantation. ClinicalTrials.gov identifier: NCT02650011.

Prognostic and diagnostic scoring models in acute alcohol-associated hepatitis: A review comparing the performance of different scoring systems.

Alcohol-associated hepatitis (AAH) is a severe form of liver disease caused by alcohol consumption. In the absence of confounding factors, clinical features and laboratory markers are sufficient to diagnose AAH, rule out alternative causes of liver injury and assess disease severity. Due to the elevated mortality of AAH, assessing the prognosis is a radical step in management. The Maddrey discriminant function (MDF) is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials. A MDF > 32 indicates a poor prognosis and a potential benefit of initiating corticosteroids. The model for end stage liver disease (MELD) score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF. The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course. Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model. Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis. AAH presenting as acute on chronic liver failure (ACLF) is so far prognosticated with ACLF-specific scoring systems. New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH. Acute kidney injury (AKI) is one possible complication of AAH and is significantly associated with increased AAH mortality. Predicting AKI and alcohol relapse are important steps in the management of AAH. The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality, emphasize the most useful tools in prognostication and review predictors of recurrence.

Correlation Between Computed Tomography Findings and the Laboratory Test-Derived Severity Score in Patients With Severe Acute Alcoholic Hepatitis.

This study aimed to compare computed tomography (CT) findings between patients with severe and nonsevere acute alcoholic hepatitis (AAH). We included 96 patients diagnosed with AAH between January 2011 and October 2021 who underwent 4-phase liver CT and laboratory blood tests. Two radiologists reviewed the initial CT images with respect to distribution and grade of hepatic steatosis; transient parenchymal arterial enhancement (TPAE); and presence of cirrhosis, ascites, and hepatosplenomegaly. A Maddrey discriminant function score (4.6 × [patient's prothrombin time - control] + total bilirubin [mg/mL]) was used as cutoff indicator for severity, with a score of 32 or higher indicating severe disease. The image findings were compared between the severe (n = 24) and nonsevere (n = 72) groups using the χ 2 test or Fisher exact test. After univariate analysis, the most significant factor was identified using a logistic regression analysis. In the univariate analysis, there were significant between-group differences in the TPAE, liver cirrhosis, splenomegaly, and ascites ( P < 0.0001, P < 0.0001, P = 0.0002, and P = 0.0163, respectively). Among them, TPAE was the only significant factor for severe AAH ( P < 0.0001; odds ratio, 48.1; 95% confidence interval, 8.3-280.6). Using this single indicator, the estimated accuracy, positive predictive, and negative predictive values were 86%, 67%, and 97%, respectively. Transient parenchymal arterial enhancement was the only significant CT finding in severe AAH.

A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

SummaryBackgroundIn trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States.MethodsThis prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections.FindingsThe study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57–0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44–0.89]; p > 0.05; CI for difference: -0.18–0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim.InterpretationThis phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone.Fundingwas provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Correction to: The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

Correction to: The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

Characteristics of immune checkpoint regulators and potential role of soluble TIM-3 and LAG-3 in male patients with alcohol-associated liver disease.

The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p=0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.

The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Clinical diagnosis of alcoholic hepatitis in Tongliao City, Inner Mongolia

Objective: To explore the current status of alcoholic hepatitis diagnosis by clinicians' in China. Methods: Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases. Results: Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively. Conclusion: Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.

Escape the EM Boards: Interactive Virtual Escape Room for GI Board Review.

This interactive and entirely virtual escape room based on high yield gastrointestinal/abdominal board review material is a didactic activity for emergency medicine residents of all postgraduate years and third- or fourth-year medical students. This escape room can be completed in small teams or as individuals in a remote, in-person, or mixed location setting. 2020 is a year that will forever change medical education. The novel coronavirus 2019 pandemic caused many national, state, local, or hospital specific recommendations for transition of meetings to be completely virtual or to only allow for limited in-person meetings. In order to abide by these recommendations, the majority of medical education transitioned to online platforms. Now more than ever, creative and engaging methods for expanding clinical knowledge and teaching teamwork as well as unique integrations of technology for medical education delivery are needed. By the end of this didactic activity, learners will be able to:Identify causes of upper gastrointestinal bleeding.Recall test-taking buzzwords for infectious causes of diarrhea.Acknowledge the correct hepatitis B titers that correspond with various clinical scenarios.Describe the management for alkali caustic ingestions.Determine the components of Maddrey Discriminant Function Score, Charcot's triad, Ranson's Criteria for Pancreatitis, and Glasgow-Blatchford Score.Diagnose specific gastrointestinal diseases from a clinical description.Choose the correct gastrointestinal diagnosis based on clinical image findings.Demonstrate teamwork in solving problems. "Gamification" is the use of game elements in a nongame context.1 Gamification creates active, engaged learning opportunities and so it is a highly favored educational method for millennial learners.1 An Escape Room is a team-based game where a small group is locked in a room and they pick up objects at random in this room to solve a series of clues that will play a role in solving the final clue to "escape" the locked room. This didactic learning activity utilizes technology to deliver a fun and interactive distance learning activity that resembles a live escape room.The interactive virtual escape room provided is a no cost, unique alternative educational activity that can be done either entirely or partly remotely. In order to replicate this team-based didactic exercise, the instructor needs to simply divide residents and students into small groups and then share with each group the link provided. A five-point Likert scale survey was distributed to participating learners after completing this activity to assess relevance and satisfaction of the high yield gastrointestinal/abdominal board review escape room. Thirty-two of forty-two participating residents/medical students completed this seven-question survey. All participating resident/medical students who completed the survey enjoyed this activity and that this was a unique learning experience, and the majority of participating residents/medical students thought this interactive virtual escape room was easy to use, learned something, thought this was a helpful way to review for emergency medicine boards or in-training exams, and preferred a game like this to a standard lecture. Additionally, over half of survey respondents said they are going to try to come up with a game for their assigned board review presentations. Escape room gamification of high yield gastrointestinal/abdominal board review material was an engaging, fun, and effective distance learning activity for residents and medical students. This didactic activity not only promoted interactive learning but also encouraged virtual teamwork among small groups. Gastroenterology, GI, abdominal, board review, in-training exam review, escape room, virtual didactics, distance learning, high yield, upper GI bleeding, esophageal varices, diarrhea, alkali ingestion, volvulus, foreign body, intussusception.

Efficacy of Phyllanthus niruri on improving liver functions in patients with alcoholic hepatitis: A double-blind randomized controlled trial.

INTRODUCTION:Phyllanthus niruri, a traditional herbal medicine, was found to be hepatoprotective as evidenced by several preclinical and clinical studies. However, to the best of our knowledge, there are no clinical trials available to date to evaluate its efficacy in alcoholic hepatitis.MATERIALS AND METHODS:The present study is a block randomized, double-blind, parallel-arm placebo-controlled trial that was designed to assess the efficacy of P. niruri on the liver and renal function parameters, total oxidant and antioxidant levels in alcoholic hepatitis patients in comparison to placebo over a 4-week period. Patients were screened by CAGE questionnaire, and those with a confirmed diagnosis of mild–moderate alcoholic hepatitis based on laboratory findings and Maddrey's discriminant function score were randomly allocated to treatment and placebo arms. Clinical assessments were done at baseline, 2 weeks, and 4 weeks. A total of 454 patients were screened and 100 eligible patients were recruited for the study, and 71 were analyzed using the modified intention-to-treat approach.RESULTS:Serum levels of liver and renal function parameters failed to demonstrate significant improvement with P. niruri. However, there was a statistically significant increase in the level of total antioxidants with P. niruri (P = 0.034) with an additional appetite stimulant activity (P = 0.03) in 4 weeks.CONCLUSION:A 4-week administration of P. niruri in mild–moderate alcoholic hepatitis patients showed an improvement in the total antioxidant levels with an appetite stimulant activity compared to a placebo.

Efficacy of Granulocyte Colony Stimulating Factor in Severe Alcoholic Hepatitis: A Systematic Review and Meta-Analysis

BackgroundSevere alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available therapeutic options. The present systematic review and meta-analysis aims to assess the survival benefit of granulocyte colony stimulating factor (G-CSF) in patients with severe alcoholic hepatitis.MethodsStudies involving adult patients receiving G-CSF for severe alcoholic hepatitis were searched in MEDLINE, Ovid journals, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model.ResultsThe initial search identified 543 reference articles; of these 24 relevant articles were selected and reviewed. Data was extracted from four studies (n = 136) which met the inclusion criteria. In the pooled analysis, the 90-day survival in the G-CSF group was 80.03% (95% CI = 69.93-88.49) compared to 40.92% (95% CI = 29.76-52.58) in the Standard Medical Therapy (SMT) group. At 28 days, the Model for End-Stage Liver Disease (MELD) score lowered by 4.89 (95% CI = 4.13-5.64) in the G-CSF group compared to 4.00 (95% CI = 3.25-4.75) in the SMT group. Child-Turcotte-Pugh score declined by 2.26 (95% CI = 1.90-2.63) in the G-CSF group after 28 days compared to 0.91 (95% CI = 0.59-1.23) in the SMT group. At 28 days, Maddrey Discriminant Function score lowered by 39.79 (95% CI = 34.22-45.36) in the G-CSF group compared to 12.39 (95% CI = 6.90-17.88) in the SMT group.ConclusionsIn patients with severe alcoholic hepatitis, G-CSF therapy resulted in significantly improved 90-day survival compared to SMT. It also demonstrated significant reduction in severity indices (Child-Turcotte-Pugh, MELD, and Maddrey discriminant function) after 28 days of treatment. There certainly is a need for further studies, including development of personalized therapeutic dosing schedules, for G-CSF administration.

31-Year-Old Woman With Jaundice and Abdominal Pain

31-Year-Old Woman With Jaundice and Abdominal Pain

An Atypical Presentation of Alcoholic Hepatitis

Significant alcohol consumption leads to a variety of alcoholic liver diseases ranging from alcoholic fatty liver disease to alcoholic cirrhosis. Alcoholic hepatitis carries a high risk of mortality; therefore, it is important to identify patients early to guide treatment and management. We discuss an atypical presentation of alcoholic hepatitis, with initial concern for lymphoproliferative disease. Our patient was a 28—year—old Cantonese—American man presenting with one month of abdominal pain, fevers, night sweats, and weight loss. His social history was not impressive for chronic alcohol use;he was a social drinker who drank 1 beer and 3 whisky shots every 4 months. Physical exam revealed tachycardia, abdominal tenderness, hepatosplenomegaly, and diffuse jaundice with no stigmata of chronic liver disease. Labs revealed leukocytosis with white blood cell count of 22x103/uL, conjugated hyperbilirubinemia (total bilirubin:4.4mg/dL), elevated alkaline phosphatase(183 U/L), and an INR of 1.43. An infectious process was ruled out when cultures and CXR were unrevealing. An abdominal ultrasound revealed hepatomegaly and ascites, but no ductal dilatation,which was confirmed on MRCP. Given his age, presence of B symptoms, and lack of significant alcohol history, there was concern for underlying malignancy. A CT abdomen showed abdominal lymphadenopathy and hepatosplenomegaly with a subsequent PET—CT scan showing diffuse lymphadenopathy and increased bone marrow activity. Hematology performed a bone marrow biopsy that revealed no signs of a neoplastic process. Patient's bilirubin continued to rise to 20mg/dL so a transjugular liver biopsy was obtained. Measurements revealed portal hypertension with HVPG of 10 and histology demonstrated steatosis, mild portal fibrosis,and Mallory body formation with neutrophilic infiltrates, suggestive of alcoholic hepatitis. The patient's Maddrey Discriminant Function score was elevated at 34 and he was started on prednisolone. At day 7 his Lille score was 0.04, indicating response to steroids. He completed a 28—day course of prednisolone and had complete resolution of fevers, ascites and biochemical abnormalities, while remaining abstinent. This is a case of alcoholic hepatitis presenting atypically with B symptoms, lack of strong drinking history, and diffuse lymphadenopathy, all suggestive of lymphoma. This case highlights the importance of pursuing a liver biopsy early on to confirm a diagnosis of alcoholic hepatitis.

Pharmacologic Treatment of Alcoholic Hepatitis: Examining Outcomes Based on Disease Severity Stratification

Maddrey discriminant function (MDF) score is a measure of disease prognosis in alcoholic hepatitis (AH) used to identify patients at highest risk of mortality and determine the need for initiation of pharmacologic treatment. The purpose of this study was to evaluate the effects of pharmacologic therapy for hospitalized AH patients as stratified by MDF score. A retrospective review of patients with an AH diagnosis admitted to a Methodist LeBonheur Healthcare adult hospital between 06/2009 and 06/2014 was conducted. Patients ≥18 years of age with an ICD-9 code for AH were evaluated. Of the 493 patients screened, 234 met the inclusion criteria, comprised of 62 patients with an MDF≥32 (treatment, n=42 vs. no treatment, n=20) and 172 patients with an MDF<32 (treatment, n=15 vs. no treatment, n=157). For the patients with an MDF≥32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (31% vs. 11%, respectively; P=0.18) and 6-month mortality (45% treatment vs. 38% non-treatment; P=0.75). For the patients with an MDF <32, there was no statistically significant difference between the treatment group vs. non-treatment group regarding 28-day mortality (0% vs. 7%, respectively; P>0.99) and 6-month mortality (11% treatment vs. 13% non-treatment; P>0.99). There was no difference in incidence of acute kidney injury, hepatorenal syndrome, development of infection or hepatic encephalopathy between the treatment vs. non-treatment groups. Pharmacologic treatment showed no survival benefit, regardless of disease severity. Given the mortality risk seen in mild-moderate AH patients not receiving treatment and concern for a possible treatment ceiling effect in severe AH patients, more data are needed to adequately assess the utility of MDF in selecting appropriate candidates for AH treatment.

Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease.

Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na <135 mM/L, albumin <2.5 g/dL, C-reactive protein ≥20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P < 0.001) higher than those without infection (22.3% vs. 5.1% and 32.3% vs. 8.2%, respectively). Furthermore, bacterial infection (HR, 2.2; 95% CI, 1.049-4.579, P = 0.037), SIRS positivity (HR, 2.5; 95% CI, 1.240-4.861, P = 0.010), Maddrey's discriminant function score ≥32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

Index of Suspicion

The reader is encouraged to write possible diagnoses for each case before turning to the discussion. We invite readers to contribute case presentations and discussions. Please inquire first by contacting Dr. Deepak Kamat at DKamat@med.wayne.edu. An 18-year-old male with a 3-year history of alcohol abuse is referred from a rehabilitation center for fever, nausea, and nonbloody diarrhea for 3 days. Six weeks ago, he enrolled in an alcohol rehabilitation program and stopped drinking alcohol. Three weeks later, he noticed yellowing of his eyes and skin, difficulty sleeping, and dyspnea. On examination, his temperature is 100.6°F (38.1°C), blood pressure is 99/62 mm Hg, pulse is 124 beats per minute, and respiratory rate is 24 breaths per minute. He is slow to answer questions. There is no asterixis. He appears thin and jaundiced with enlarged parotid glands. Decreased breath sounds are noted on the right. A tender, enlarged liver and mild abdominal distension are noted. Trace bilateral lower-extremity edema is present. No stigmata of chronic liver disease are found. Laboratory findings reveal the following: white blood cell count, 25,600/μL (25.6 × 109/L) (87% neutrophils); hemoglobin, 8.2 g/dL (82 g/L); mean corpuscular volume, 106 fL; platelets, 40 × 103/μL (40 × 109/L); sodium, 135 mEq/L (135 mmol/L); potassium, 3.5 mEq/L (3.5 mmol/L); chloride, 106 mEq/L (106 mmol/L); bicarbonate, 15 mEq/L (15 mmol/L); blood urea nitrogen, 24 mg/dL (8.6 mmol/L); creatinine, 1.01 mg/dL (89 μmol/L); glucose, 118 mg/dL (6.6 mmol/L); alkaline phosphatase, 182 U/L; aspartate aminotransferase (AST), 194 U/L; alanine aminotransferase (ALT), 71 U/L; total bilirubin, 11.8 mg/dL (201.8 μmol/L); direct bilirubin, 7.3 mg/dL (124.9 μmol/L); albumin, 2.7 g/dL (27 g/L); prothrombin time, 19.2 seconds; and international normalized ratio, 1.4. Ethanol and acetaminophen were not detected in the serum. A chest radiograph reveals a right pleural effusion …

Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for Severe Alcoholic Hepatitis: A Randomized Controlled Clinical Trial.

Background:Prednisolone and pentoxifylline (PTX) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function (MDF) score ≥32. Previous report suggests that PTX is probably superior to prednisolone alone. However the efficacy of PTX and prednisolone combination over PTX alone in the management of acute alcoholic hepatitis (MDF score ≥32) is yet unrevealed.Aim:The present study was initiated to find out the efficacy of combined pentoxifylline and prednisolone versus PTX alone in acute alcoholic hepatitis in respect of short and intermediate term outcomes.Subjects and Methods:A total of 124 patients with severe alcoholic hepatitis (MDF score ≥ 32) initially were evaluated. 62 patients who fulfilled the inclusion and exclusion criteria were randomized and divided into 2 groups. Group 1 received PTX only, whereas Group 2 received PTX plus Prednisolone. The total duration of follow-up was 12 months. Student's t-test, Chi-square test, the Kaplan-Meier methods were used for statistical analysis.Results:A total of 60 patients, 30 in each group were available for final analysis. In Group-1, 6 patients expired at the end of 1 year (5 within 3 months and another after 3 months). In Group 2, 10 patients expired at the end of 1 year (9 within 3 months and another after 3 months). Though survival probability is higher among Group 1 patients but the difference is not statistically significant.Conclusion:The combination of PTX plus Prednisolone yields no additional benefit in terms of mortality and morbidity from that of PTX monotherapy.

Clinical and histological recovery from "life-threatening" severe acute alcoholic hepatic failure with complete hepatofugal portal blood flow.

A 25-year-old man who was a heavy alcohol drinker was admitted to our hospital after presenting with general malaise, dyspnea, abdominal distension, systemic edema and jaundice. His liver function tests showed hyperbilirubinemia and prolonged prothrombin time, and a computed tomography scan and ultrasound showed liver atrophy and massive ascites. Furthermore, Doppler ultrasound revealed complete hepatofugal portal blood flow in the portal trunk and intrahepatic portal branches. Causes other than alcohol were excluded, and he was diagnosed as having severe acute alcoholic hepatic failure (Maddrey's discriminant function score 43.3, MELD score 21), although not clinically typical. He was treated with anti-coagulation therapy according to the precise evaluation of portal blood flow by Doppler ultrasound, and marked clinical, biochemical and hemodynamic improvements were observed. Liver biopsy performed 2months after onset showed submassive necrosis with pericellular fibrosis. Liver biopsy performed three years after onset showed mild portal fibrosis with a marked improvement. Doppler ultrasound is an indispensable tool for evaluating patients with severe acute hepatitis.

Pentoxifylline: A first line treatment option for severe alcoholic hepatitis and hepatorenal syndrome?

Although favourable results of pentoxifylline (PTX) used in treatment of severe alcoholic hepatitis patients with a Maddrey discriminant function score > or = 32 have been previously reported, it is not currently recommended as a first line treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as compared to the standard treatment with corticosteroids. In a very recent issue of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the first time the two treatment modalities head to head in a randomized controlled study, demonstrating the advantage of PTX over corticosteroids in terms of patients' survival and risk-benefit profile. The advantage of PTX over corticosteroids in survival of patients with severe alcoholic hepatitis was found to be related to the prevention of hepatorenal syndrome in their study. This study raises the question of the use of PTX as a standard treatment for severe alcoholic hepatitis. Considering the fact that PTX presented a spectacular efficiency in prevention of hepatorenal syndrome in their study as well as that previous studies have shown that this effect is possibly related to a primary renoprotective action because it is irrelevant of tumor necrosis factor-alpha synthesis inhibition or improved liver function, we tempted to speculate that PXT might be an effective option for prevention and/or treatment of hepatorenal syndrome complicating other forms of advanced liver disease. This attractive theory remains to be elucidated by pressing future studies in view of the lack of effective treatment modalities for hepatorenal syndrome.

Predicting utility of a model for end stage liver disease in alcoholic liver disease

To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term (30 d and 90 d) mortality in patients with alcoholic hepatitis and to assess prognostic factors among clinical characteristics and laboratory variables of patients with alcoholic hepatitis. Thirty-four patients with the diagnosis of alcoholic hepatitis admitted to Hippokration University Hospital of Athens from 2000 to 2005 were assessed in the current retrospective study and a statistical analysis was conducted. 30- and 90-d mortality rates were reported at 5.9% (2/34) and 14.7% (5/34), respectively. Significant correlation was demonstrated for the Model for End-Stage Liver Disease (P30 = 0.094, P90 = 0.046) and the Maddrey Discriminant Function score (P30 = 0.033, P90 = 0.038) with 30- and 90-d mortality whereas a significant association was also established for alanine aminotransferase (P = 0.057), fibrin degradation products (P = 0.048) and C-reactive protein (P = 0.067) with 90-d mortality. For 30-d mortality the Area Under the Curve was 0.969 (95%CI: 0.902-1.036, P = 0.028) for the Model for End-Stage Liver Disease score and 0.984 (95%CI: 0.942-1.027, P = 0.023) for the Maddrey Discriminant Function score with the optimal cut off point of 30.5 (sensitivity 1, specificity 0.937) and 108.68 (sensitivity 1, specificity 0.969), respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762 (95%CI: 0.559-0.965, P = 0.065) for the Model for End-Stage Liver Disease score and 0.752 (95%CI: 0.465-1.038, P = 0.076) for the Maddrey Discriminant Function score with the optimal cut off point of 19 (sensitivity 0.6, specificity 0.6) and 92 (sensitivity 0.6, specificity 0.946), respectively. The observed Kaplan Meier survival rates for different score-categories were compared with log-rank tests and higher score values were correlated with a lower survival. Equivalency of the Model for End-Stage Liver Disease and the Maddrey Discriminant Function score is implied by the current study, verified by the plotted Receiver Operative Curves and the estimated survival rates. A statistically significant utility of C-reactive protein, fibrin degradation products and alanine aminotransferase as independent predictors of 90-d mortality has also been verified.