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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes.

OBJECTIVES: The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival. METHODS: North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival. RESULTS: 653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality. CONCLUSIONS: Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation.

BACKGROUND: It has been suggested that beta-blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta-blockers discontinuation or reinitiation has not been examined. AIMS: To compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta-blockers discontinuation and reinitiation. METHODS: Sub-analysis of NACSELD (North American consortium for the study of end-stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling >100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review. RESULTS: Seven hundred and sixteen patients, 307 (43%) on beta-blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta-blocker use was associated with a lower white blood cell count at admission. Beta-blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta-blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta-blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP. CONCLUSIONS: Beta-blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta-blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti-inflammatory effect of beta-blockers is suggested.

Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility.

Nitric oxide (NO) has been implicated in the arterial vasodilation and associated vascular hyporesponsiveness to vasoconstrictors observed in liver cirrhosis. Bacteria, potent activators of NO and TNF-alpha synthesis, are found in the mesenteric lymph nodes (MLNs) of ascitic cirrhotic rats. Here, we investigated the impact of bacterial translocation (BT) to MLNs on TNF-alpha production, vascular NO release, and contractility in the mesenteric vasculature of ascitic cirrhotic rats. Vascular response to the alpha-adrenoagonist methoxamine, which is diminished in the superior mesenteric arterial beds of cirrhotic rats, is further blunted in the presence of BT. BT promoted vascular NO release in cirrhotic rats, an effect that depended on pressure-induced shear stress and was blocked by the NO inhibitor N(omega)-nitro-L-arginine. Removing the endothelium had the same effect. Endothelial NO synthase (eNOS), but not the inducible isoform (iNOS), was present in mesenteric vasculature of cirrhotic rats with and without BT, and its expression was enhanced compared with controls. TNF-alpha was induced in MLNs by BT and accumulated in parallel in the serum. This TNF-alpha production was associated with elevated levels of tetrahydrobiopterin (BH(4)), a TNF-alpha-stimulated cofactor and enhancer of eNOS-derived NO biosynthesis and NOS activity in mesenteric vasculature. These findings establish a link between BT to MLNs and increased TNF-alpha production and elevated BH(4) levels enhancing eNOS-derived NO overproduction, further impairing contractility in the cirrhotic mesenteric vasculature.

Clinical management of ascites and its complications.

Development of ascites is a poor prognostic sign with a 1 year mortality rate of up to 50%. Cirrhotic patients who develop ascites should therefore be evaluated for liver transplantation. Even though current therapies of ascites are not associated with a survival benefit, the elimination of ascites will improve quality of life and prevent the development of lethal complications such as SBP and HRS. Therapy of ascites should be directed at correcting the pathophysiologic abnormalities that lead to ascites formation, namely sodium retention, reduced effective arterial blood volume, and sinusoidal hypertension.

A study with quinfamide in the treatment of chronic amebiasis in adults.

Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-mg doses, each given three times daily. A cure rate of 100% was found at a dosage of 100 mg/8 hr and of 93.3% at 200 mg/8 hr. These results indicate that quinfamide is an effective luminal amebicide at the doses studied.

Elective treatment of bleeding varices with the Sugiura operation over 10 years.

A 10-year experience with the devascularization operation described by Sugiura is reported here. The operation was performed electively in 100 patients in whom it was not possible to place a shunt, all of whom had different kinds of hepatopathies (63 Child's A, 32 Child's B, and 5 Child's C). In 15 patients, the procedure was done in one stage (6% operative mortality, 1 patient), and, in 51, it was performed in two stages. Eight deaths were recorded in the 63 patients of the Child's A group, with a total of 111 operations. The operative mortality rate for this group was 12% and, as related to the number of operative procedures, 7% (8 of 111 operations). Seventeen patients were not considered for a second stage. Rebleeding in the early postoperative period was 4% and at long-term 6%. Incapacitating encephalopathy was found in 2 of the 71 surviving patients (3%). Survival (as determined by Kaplan-Meier tests) was 75% (1 year), 70% (5 years), and 69.2% (10 years). Six esophageal fistulas were observed secondary to transection. The Sugiura operation is an excellent complement to the therapeutic armamentarium used to treat portal hypertension, with low rebleeding and encephalopathy rates.

Role of the distal splenorenal shunt in management of variceal bleeding in Latin America.

In the early 1970s, we began to perform selective shunts on a regular basis for the treatment of portal hypertension. In a 15-year period, 177 patients (155 with liver cirrhosis) were treated with 3 kinds of selective shunts: the Warren shunt (128 patients) the end-to-end splenorenal shunt (29 patients), and the splenocaval shunt (20 patients). One hundred sixty-seven of the procedures were elective. Operative mortality was 14%, and survival for the Child's class A group was 75% at 1 year, 69% at 5 years, and 65% at 15 years. Incapacitating encephalopathy was observed in 7% of the patients, rebleeding in 6%, and shunt thrombosis in 6%. Postoperative portal vein alterations included reduced venous diameter (13%) and thrombosis (21%). Experience with the Warren shunt in schistosomiasis, a disease in which normal liver function is the rule in Latin American countries, is discussed. We believe that, when feasible, the selective shunts are the treatment of choice for portal hypertension in Latin American countries.

Doppler ultrasound in the evaluation of cirrhotic patients: the prevalence of intrahepatic arteriovenous shunting, and implications for diagnosis of hepatocellular carcinoma.

To establish the prevalence and significance of Doppler-detected hepatic arteriovenous shunting (AVS) in patients with compensated cirrhosis, 115 patients (mean age 55.4 +/- 12.47 SD y) were prospectively screened using real-time ultrasound with pulsed Doppler at 2.5 MHz to detect focal liver lesions and quantify AVS. Focal masses were biopsied and correlated with the US findings. All other patients had clinical follow-up and imaging for at least 12 months. AVS occurred in 28 of 115 (24.3%), and in 18 of 20 proven malignancies (90%) including 11 of 13 cases of hepatocellular carcinoma (85%). However, 9 of 28 (32%) AVS (mean Doppler shift 2.73 +/- 1.51 [SD] kHz [range 0.6-5.41 kHz], n = 9) were in regions of fatty infiltration (4) or isolated (5), unassociated with malignancy. At a prevalence of 17.9% malignancy (11.3% due to hepatocellular carcinoma), specificity for malignancy increased with shunt velocity, from 76% (for mass alone), to 94.8% for mass with AVS, 96.8% for a mass with AVS of 1.75-2.4 kHz, and 100% for a mass with AVS > 2.4 kHz. Doppler US is useful in characterizing liver lesions in cirrhotic patients: the majority of malignant hepatic lesions are associated with AVS and specificity for malignancy increases with shunt velocity. However, isolated AVS or AVS associated with focal fat may be detected in 7.8% of compensated cirrhotics.

Variceal hemorrhage.

Variceal hemorrhage is a complication of portal hypertension that has high mortality and high recurrence rates. Management of variceal bleeding involves three areas: treatment of active hemorrhage, prevention of rebleeding, and prevention of first variceal bleeding. There are two main therapeutic avenues: methods directed at reducing portal pressure, such as pharmacologic therapy, shunt surgery, and TIPS; and methods that act locally by decreasing or interrupting blood flow through a specific varice, such as sclerotherapy, banding, and balloon tamponade. The relative effectiveness of each of these interventions is discussed in this article.

Viral RNA in duodenal bile of cirrhotic patients with chronic hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) has been detected in blood, saliva, urine, semen, breast milk, and tears. To our knowledge, bile has not yet been investigated. We observed histologic immunoreactivity in bile with an antibody to c100 protein in four of five HCV-positive cirrhotic livers, but also in two HCV-negative controls owing to a focally present cross-reacting antigen. METHODS: We collected duodenal bile from 13 cirrhotic patients during endoscopic evaluation of varices (10 HCV, three controls) and assayed for HCV by reverse transcriptase polymerase chain reaction. RESULTS: Viral RNA was detected in the bile of 8 of 10 seropositive patients and in 0 of 3 seronegative controls. CONCLUSION: Hepatitis C virus RNA and an antigen immunoreactive with anti-c100 protein are present in bile in a proportion of cirrhotic patients with chronic HCV. It remains to be determined whether the virus is intact or degenerate, and whether it is shed into bile from hepatocytes or is a contaminant from blood or other secretions.

Partial hepatectomy for Caroli's syndrome. Report of two patients with long-term follow-up.

Caroli's syndrome comprises cystic dilatations of the intrahepatic bile ducts, which may be focal or diffuse. Partial hepatectomy, when possible, is the best current treatment. We report on two patients with Caroli's syndrome confined to one side of the liver, who were subjected to partial hepatectomy. Both patients had a previous history of biliary tract surgery. Transhepatic percutaneous cholangiography and abdominal CT scan were helpful in establishing the diagnosis and the extent of the disease. After hepatectomy, one patient developed an abdominal abscess that required surgical drainage, the other developed persistent fever, which resolved spontaneously. Both patients are asymptomatic three and five years post-hepatectomy, respectively, and there is no clinical evidence of recurrence of the disease. The diagnostic work-up and therapeutic choices for this rare entity are discussed.

[Hepatic fibropolycystic disease in Mexico. Study of 82 cases]. / Enfermedad fibropoliquística hepática en Mexico. Estudio de 82 casos.

We analyzed 82 cases of hepatobiliary fibropolycystic disease (FPD) that were seen at the Instituto Nacional de la Nutrición "Salvador Zubirán" in Mexico City in the thirty-year period comprised from 1956 to 1986. The different entities that compose FPD were distributed as follows: 61 (74%) cases of polycystic liver disease, 13 (16%) cases of choledochal cyst, and 8 (10%) cases of congenital hepatic fibrosis; there were 5 (6%) cases of Caroli's disease, 3 associated with congenital hepatic fibrosis and 2 with choledochal cyst. Polycystic liver disease predominated in females (67%) and presented at 54 +/- 12 years (mean +/- SEM) with pain, a mass, symptoms related to renal insufficiency or incidentally; polycystic kidneys were present in 61%. Liver function tests were normal in 94%. Choledochal cyst also predominated in females and presented at a mean age of 19 years with cholangitis. Liver function tests were abnormal in 69%. Congenital hepatic fibrosis (50% male) presented with variceal hemorrhage or cholangitis (in 3 patients associated with Caroli's disease). Polycystic kidneys were present in five patients. Four of the five patients with Caroli's disease were female and presented at a mean age of 19 years with cholangitis. It never presented as an isolated disease, but was associated more frequently to congenital hepatic fibrosis. The diseases that are part of the hepatobiliary polycystic disease vary in severity and thus the prognosis in an individual patient is determined by the type of fibropolycystic disease present. This is the largest series of this disease published in our country.

[Idiopathic portal hypertension]. / Hipertensión portal idiopática.

Patients with portal hypertension without a demonstrable cause have been reported in the literature under several different terms, such as tropical splenomegaly, phlebosclerosis, obliterative portal venopathy of the liver, hepatoportal sclerosis, noncirrhotic portal fibrosis and idiopathic portal hypertension (IPH). Such patients have been described worldwide, with a greater frequency in India and Japan. The etiology of IPH is still unknown, although some of the theories that have been proposed are: exposure to toxic substances or drugs, relationship with the hepatitis-B virus, immunologic abnormalities, systemic or intra-abdominal infections and clotting abnormalities. The main histopathologic findings are periportal fibrosis, obliteration of small portal veins and sclerosis of the interhepatic portal system. Although these abnormalities could be secondary to portal hypertension, it has been proposed that the vascular changes are the primary event that leads to portal hypertension. The site of increased resistance in IPH is found at the presinusoidal level with some component at the sinusoidal and postsinusoidal level. The main symptoms and signs in IPH are upper gastrointestinal tract bleeding secondary to esophago-gastric varices, symptoms related to anemia, and splenomegaly. The long-term prognosis for patients with IPH is better than for cirrhotic patients, with a 77% survival at ten years. Variceal bleeding is the main cause of death, and some treatment to prevent bleeding or its recurrence is warranted. Although no comparative trial has been performed in IPH patients, the surgical management could be the first choice for elective treatment in these patient without liver failure, because of the high re-bleeding rates with chronic sclerotherapy. Pharmacologic management could be considered for prophylactic treatment of these patients.

[Selective portal-systemic shunts for bleeding portal hypertension]. / Derivaciones portosistemicas selectivas en el manejo de la hemorragia por varices esofagogastricas.

At the beginning of the seventies, we began to perform regularly selective shunts for the treatment of portal hypertension. In a 15 year period, 177 patients (155 with liver cirrhosis) were operated with three kinds of selective shunts: 128 with a Warren shunt, 29 with an end to end renosplenic shunt and 20 with a splenocaval shunt. 167 cases were operated in an elective fashion. The 15 years global operative mortality, was 14.4%. Operative mortality of the Child A patients, was 11.6%. Survival for the Child A group was 74.6% at 1 year, 68.2% at 5 years and 64.6% at 15 years. Incapacitating encephalopathy was observed in 6.9%, rebleeding 6.2% and shunt thrombosis in 6.2%. Portal vein alterations in the postoperative period were observed: in 13.3% a reduction in diameter ocurred and in 20.5%, thrombosis was recorded. It is concluded that when feasible, the selective shunts are the treatment of choice for portal hypertension in those patients with good liver function.

[Usefulness of the histologic and microbiologic study of liver biopsy in the diagnosis of fever of unknown origin]. / Utilidad del estudio histológico y microbiológico de la biopsia hepática en el diagnóstico de la fiebre de origen desconocido.

Since the usefulness of liver biopsy in the diagnosis of fever of unknown origin is still controversial, we analyzed the charts of 54 patients with fever of unknown origin in whom histological and microbiological studies of a liver biopsy were performed. The cause of fever was established in 43 (80%) patients and it was most frequently of an infectious origin (52%). Histological analysis of liver biopsy was useful in determining the final diagnosis in 26 patients (48%) and was the main/only diagnostic method in a third of them. It was useful even in patients with no evidence of hepatic disfunction. Microbiological analysis of liver biopsy was positive in 7 cases (25% of infectious causes). We consider that liver biopsy should be performed early in the work-up of patients with fever of unknown origin.

[Surgical treatment of hemorrhage of esophageal varices secondary to thrombosis of the portal vein]. / Tratamiento quirúrgico de la hemorragia por várices esofágicas secundarias a trombosis de la vena porta.

The Sugiura Procedure (SP) was performed in 27 patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis without associated liver disease (EPVT). There were fourteen females and 13 males. Mean age was 28 +/- 14 years. The causes of EPVT were: protein C deficiency-2 cases, antithrombin III deficiency-1 case, omphalitis history-2 cases, pancreatitis history-1 case and idiopathic-21 cases. The SP was completed with two surgical stages in 14 patients and with one operation in nine. There was one operative death. One patient developed mild postoperative encephalopathy, and two patients re-bled at long-term. Actuarial survival was 82% at five and ten years. It is concluded that the SP is a good alternative for the management of hemorrhagic portal hypertension secondary to EPVT.