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.

Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis.

BACKGROUND: Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the presence of multiple susceptibility factors. PCT presents clinically with cutaneous blistering photosensitivity and is readily treatable with either repeated phlebotomy or 4-aminoquinoline antimalarials. OBJECTIVES: To perform a systematic review and meta-analysis to compare the effectiveness of these quite different treatment approaches, especially on relapse rates (RRs) after achieving remission. METHODS: Published studies that included follow-up for at least 1 year after treatment of PCT were included. The primary study outcome was PCT relapse. Pooled data are reported as the RRs per person-year of follow-up with 95% confidence intervals (CIs). RESULTS: Of 375 articles identified as pertaining to PCT treatment, 12 were eligible for analysis. Of these, five used high-dose 4-aminoquinoline regimens (two combined with phlebotomy and three without phlebotomy), five used low-dose 4-aminoquinoline regimens and three used phlebotomy. RRs during the year after treatment were similar for the high- and low-dose 4-aminoquinoline groups (35-36%) and lower in the phlebotomy group (20%). The pooled RRs with their 95% CIs were 8·6 (3·9-13·3) per 100 person-years in the high-dose 4-aminoquinoline group, 17·1 (8·9-25·3) per 100 person-years in the low-dose 4-aminoquinoline group and 5·1 (0·5-10·6) per 100 person-years in the phlebotomy group. Subgroup and sensitivity analyses showed similar results. CONCLUSIONS: Clinical or biochemical RRs ranged from 5 to 17 per 100 person-years after remission of PCT. Relapses were somewhat more frequent after remission with 4-aminoquinoline regimens than after remission following phlebotomy. Prospective studies are needed to define better how often relapses occur with these treatments after documenting both clinical and biochemical remission of PCT.

Optimal management of alcoholic hepatitis.

Alcoholic hepatitis, a clinical syndrome among people with chronic and active alcohol abuse presents with with jaundice and liver failure with or without hepatic encephalopathy. In patients with severe episode, this condition has a potential for 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options provide only about 50% survival benefit. Response to corticosteroids can only be assessed at 1 week of initiation of these drugs using Lille score or documentation of improvement in bilirubin levels. Requirement of minimum 6 months abstinence for liver transplantation cannot be met for alcoholic hepatitis patients who fail to respond to steroids. Emerging data on the benefit of liver transplantation for select patients with first episode of severe AH with non-response to steroids are encouraging. There remains an unmet need for studies assessing newer therapeutic targets and drugs and for optimizing the currently available treatment options. In this regard, decision to promote clinical and translational research by the National Institute of Alcohol Abuse and Alcoholism will be helpful in improving survival of patients with alcoholic hepatitis.

Urethral duplication in association with anorectal malformation.

Urethral duplication is an uncommon congenital anomaly, not often reported, which may be partial or complete. Anorectal malformations are not as uncommon and they may be associated with a host of associated anomalies. However, the association of urethral duplication with anorectal malformation is rare; this report describes two such cases. In one case the intervening septum could be incised endoscopically and in the other case the duplicated urethra was excised.

Symptomatic hepatic hemangioendothelioma in a newborn.

A case of hepatic hemangioendothelioma presenting as congestive cardiac failure in a neonate is reported. There was also evidence of platelet consumption. The case was managed successfully with oral prednisolone, resulting in improvement of symptoms and tumor regression over 3 months.

Management of hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management. METHODS: Literature search for publications especially over the last decade, which has changed the paradigm on the management of HCC. RESULTS: Hepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control. CONCLUSIONS: In spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.

Cimetidine in the treatment of non-ulcer dyspepsia: results of a randomized double-blind, placebo-controlled study.

A randomized double-blind, placebo-controlled study was carried out in 56 patients with essential dyspepsia to investigate the therapeutic efficacy of cimetidine in providing symptomatic relief. Patients received either 1 tablet of cimetidine (400 mg) or identical looking placebo twice daily for a period of 4 weeks. A detailed symptomatic assessment was made at weekly intervals. Abdominal pain, the primary symptom, was relieved in a higher proportion of cimetidine-treated patients compared to placebo group (67% versus 40%, p less than 0.05). Most of the secondary gastro-intestinal symptoms also improved in a higher proportion of patients in the cimetidine group although the difference was statistically not significant. The outcome of treatment was not influenced by factors such as duration of disease, initial severity of pain and smoking habits of the patient.

Splenoportovenography: safety, success rate and hemodynamic changes, and incidence and natural history of splenic hematoma.

Forty-five non-cirrhotic patients undergoing splenoportovenography (SPV) were studied. SPV was performed successfully in 43 (95.5%) patients. Local pain was encountered in 12 (26.6%) and lasted for a mean (+/- SD) of 7 +/- 3.8 hours. Local tenderness was noted in 17 (37.7%) and lasted for 6.8 +/- 3.7 hours. The mean rise in the pulse rate after the procedure was 6.5 +/- 4.7 beats per minute and the fall in the systolic and diastolic blood pressures was 3.4 +/- 2.5 and 0.8 +/- 1.7 mmHg respectively. Post-SPV splenic hematoma was noted in 3 (6.6%) patients. All were subcapsular, at the site of puncture, and disappeared by the seventh day. There was no difference in the age, change in the pulse rate, and fall in systolic or diastolic blood pressures between those who developed and those who did not develop hematoma. One patient required one unit of blood transfusion. There were no deaths. SPV was noted to be a simple and safe procedure with a high success rate with minimal morbidity and no mortality.

Traveler's diarrhea-I. Definition, etiology and epidemiology.

With the development of rapid and convenient means of transportation, several million persons travel from industrialized countries to developing countries every year. From USA alone, approximately 4 million persons visit Mexico annually. These travelers are at risk to develop several infections during their stay abroad, but the most commonly experienced illness is diarrhea. The attack rate of diarrhea in travelers may be as high as 25 to 50 percent; 30 percent of those who get diarrhea are ill enough to be confined to bed and another 40% have to change their scheduled travel plans. The disease affects all ranks and it has achieved worldwide fame by its several euphemisms. Various epithets used to describe this illness include GI trots, Aden gut, Barsa belly, Turkey trot, Delhi belly, Hongkong dog, Montezuma's revenge, gyppsy tummy and turista. There have been considerable advances in our understanding about the etiology and epidemiology of this disease in the last two decades and the purpose of this review is to highlight some of this new information.

Diffuse intra-abdominal fibromatosis-report of a new entity with review of literature.

Fibromatosis, arare non-neoplastic spindle cell proliferation of unknown aetiology, can occur anywhere in the body. Though extra-abdominal sites are commonly involved, intra-abdominal fibromatosis has also been described. Described herein is an unusual case of diffuse intra-abdominal fibromatosis in a 9-year-old boy, who could not be salvaged despite extensive medical management.

Prevalence and in-hospital mortality trends of infections among patients with cirrhosis: a nationwide study of hospitalised patients in the United States.

BACKGROUND: Data on bacterial infections in hospitalised patients in the US with cirrhosis are derived largely from single centre data. Countrywide data in this population are lacking. AIM: To assess prevalence of infections among hospitalised patients in the US and examine their impact on in-hospital mortality and health care resources utilisation. METHODS: Nationwide Inpatient Sample (1998-2007) was queried for hospitalisations with cirrhosis and examined for infections including spontaneous bacterial peritonitis (SBP), urinary tract infection (UTI), skin and soft tissue infections, pneumonia and Clostridium difficile infections (CDI). In-hospital mortality, length of stay (LOS) and total charges were analysed. RESULTS: Of 742,391 admissions with cirrhosis, 168,654 (23%) had discharge diagnosis of any infection. Between 1998 and 2007, there was a trend towards increasing prevalence of infections (21-25%). Higher rates of infection were associated with ascites (22-25%) and renal insufficiency (RI) (38-43%). Infection with RI increased from 13% in 1998 to 27% in 2007. UTI was the most common infection (9-12%) followed by subcutaneous tissue infections (5-6%) and SBP (2-3%, around 12% in patients with ascites). Infection rate was similar among teaching and nonteaching hospitals with CDI and SBP being more common in teaching hospitals. In-hospital mortality was about 5%, over fivefold higher in infected cirrhotics, and associated with higher LOS and charges. Sepsis (38-42%), pneumonia (23-30%), SBP (16-23%) and CDI (11-16%) contributed most to in-hospital mortality. CONCLUSIONS: The prevalence of infections among hospitalised patients with cirrhosis in the US is increasing and is associated with in-hospital mortality, renal insufficiency and costs.

Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B.

BACKGROUND: Five oral nucleos(t)ide analogues are available to treat chronic hepatitis B (CHB). With the availability of newer agents, their efficacy on incidence of hepatocellular carcinoma (HCC) is not well described. AIM: To determine the efficacy of oral anti-viral agents in reducing HCC risk in relationship with other known factors. METHODS: Published studies of at least 20 CHB patients treated with an oral anti-viral agent and followed for >2 years were analysed for incidence of HCC per 100 person years follow-up. RESULTS: Pooled homogeneous data from six studies showed lamivudine (LAM) treatment (n = 3306) to reduce HCC risk by 51% compared with no treatment (n = 3585) (3.3 vs. 9.7 per 100 person years, P < 0.0001). Pooled data from 49 studies (23 with LAM; 16 with adefovir; and 10 with entecavir, tenofovir or telbivudine) of 10 025 treated patients showed HCC incidence of 1.3 per 100 person years, independent of the agent used. Patient age >50 years and hepatitis B virus-DNA detectability at HCC diagnosis increased risk of HCC by twofold with a 10-fold higher risk among patients with cirrhosis compared with chronic hepatitis. Meta-regression showed patient age, study location (Eastern vs. Western) and type of study (randomised or not) contributed to heterogeneity. CONCLUSIONS: Lamivudine treatment significantly reduces the incidence of HCC compared with no treatment. However, HCC still develops at a rate of 1.3 per 100 patient years in CHB patients receiving an oral anti-viral agent. This finding highlights the need for continued HCC surveillance, particularly in CHB patients with inadequate viral suppression, older age and cirrhosis.

Meta-analysis: oral anti-viral agents in adults with decompensated hepatitis B virus cirrhosis.

BACKGROUND: The optimal oral anti-viral agent to use in patients with decompensated HBV cirrhosis remains unclear. AIM: We performed a meta-analysis of the oral nucleos(t)ide analogues in patients with decompensated HBV cirrhosis. METHODS: One year efficacy and safety outcomes in 22 studies published in English between '95 and 2010 were analysed. RESULTS: Substantial heterogeneity was noted in the inclusion/exclusion criteria, controls, and sensitivity of the HBV DNA assay used. Pooled 1-year data showed benefit favouring lamivudine (LAM) vs. untreated controls for Child-Turcotte-Pugh (CTP) score improvement by ≥2 (OR: 117 (15 921), P ≤ 0.0001) and transplant-free survival (OR: 3.2 (1.2, 9), P = 0.022). Adefovir (ADV) led to undetectable HBV DNA at 1-year in 41% compared to 83% with LAM and 80% with entecavir (ETV). Overall, 1-year transplant-free survival rates varied from 78% with LAM to 95% and 94% with Tenofovir (TDF) and Telbivudine (TBV), respectively. The 1-year incidence of drug resistant HBV was 0% with ADV, ETV and TDF and 11% with LAM although TBV was associated with a 29% incidence at 2 years. Drug-related adverse events were infrequently reported. CONCLUSIONS: All the oral anti-viral agents were associated with improved virological, biochemical and clinical parameters at 1-year. However, the efficacy of lamivudine and telbivudine is limited by drug resistance, and adefovir is limited by its potency and slower onset of action. Additional studies of tenofovir and entecavir are needed to determine the optimal agent(s) for treatment naïve patients and in those with drug-resistant decompensated HBV cirrhosis.

Natural history of small duct primary sclerosing cholangitis: a case series with review of the literature.

BACKGROUND AND AIMS: Information about the natural history of small duct primary sclerosing cholangitis (SDPSC) remains scant despite literature suggesting that it constitutes 6-16% of all cases of primary sclerosing cholangitis (PSC). We combined clinical data on SDPSC cases from two tertiary care institutions with liver transplantation programs with the aim of studying the natural history of SDPSC. METHODS: Medical records of 25 individuals with SDPSC were reviewed. Diagnosis of SDPSC was based on liver biopsy findings consistent with PSC, a normal cholangiogram, and elimination of known causes of secondary sclerosing cholangitis. Demographic information, symptoms, past medical history, laboratory values, and histologic data were evaluated. Our primary outcome measure was liver transplantation or death. Secondary outcome measures included evidence of end-stage liver disease, development of cholangiocarcinoma, and/or the development of classic PSC on a repeat cholangiogram. RESULTS: Data on 25 individuals (13 males, 12 females; mean age 40 ± 15 years) diagnosed with SDPSC were analyzed. Upon presentation, 11 patients had symptoms including abdominal pain, fatigue, and pruritus. Inflammatory bowel disease was present in 14 patients (56%) at diagnosis. On initial liver biopsy, 60% had early-stage disease (I or II) and none had cirrhosis. On follow-up (1-168 months, median 17 months), malignancy or progression to classic large duct PSC was not noted. Two (8%) patients had evidence of varices and one of the two also developed ascites; one of these patients underwent liver transplantation and the other one died due to sepsis. CONCLUSIONS: SDPSC, a mild disease at presentation typically runs a benign course and likely is not an early stage of classic PSC. Further studies with a control group of classic PSC and longer follow-up are needed to study the natural history of SDPSC.

Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is third most common cause of tumour-related death in the US with hepatitis C virus (HCV) the most common aetiology. Surgical resection and tumour ablation are curative in patients who cannot be transplanted. With native liver having cirrhosis, HCC recurrence is a potential problem. AIM: To perform a systematic review and meta-analysis of studies evaluating efficacy of IFN to prevent HCC recurrence after its curative treatment in HCV-related cirrhosis. METHODS: Ten studies (n = 645, 301 treated with IFN) on the use of IFN after resection or ablation of HCV-associated HCC were analysed. RESULTS: Pooled data showed benefit of IFN for HCC prevention with OR (95% CI) of 0.26 (0.15-0.45); P < 0.00001. The proportion of patients surviving at 5 years (n = 505 in 6 studies) was in favour of IFN with OR of 0.31 [(95% CI 0.21-0.46); P < 0.00001]. Data were homogeneous for HCC recurrence (chi(2) 12.05, P = 0.21) and survival (chi(2) 6.93, P = 0.44). The benefit of IFN was stronger with sustained virological response compared with nonresponders for HCC recurrence [0.19 (0.06-0.60); P = 0.005] and survival [0.31 (0.11-0.90); P = 0.03]. CONCLUSION: Interferon treatment after curative resection or ablation of HCC in HCV-related cirrhotics prevents HCC recurrence and improves survival.