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.

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.

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.

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.

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.

Laparoscopic management of neonatal gastric volvulus: a case report and review of the literature.

We report a neonate who presented with failure to thrive, non-bilious vomiting and upper abdominal distension starting at one week of age. A barium upper GI study confirmed the diagnosis of organoaxial volvulus of the stomach, and the child underwent a successful laparoscopic gastropexy. At one year of follow-up the child is asymptomatic. We discuss the technique and review the literature.

Antenatally diagnosed ovarian cyst with torsion managed laparoscopically.

Ovarian cyst are the most common intra-abdominal cyst in female neonate. With the help of ultrasound one can make an antenatal diagnosis. We present one such neonate, she was managed by laparoscopic excision. We conclude that neonatal laparoscopy is technically feasible for management of such cysts.

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol.

BACKGROUND: Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS). AIM: To evaluate whether OSPS is associated with changes in renal function. METHODS: A chart review performed on 311 patients who had colonoscopy at the James J. Peters VA Medical Centre prepared with either OSPS (n = 157) or polyethylene glycol (PEG) (n = 154). Patients had a baseline serum creatinine or=50% increase above their baseline creatinine was similar (OSPS vs. PEG, 5% vs. 3%, P = 0.77). CONCLUSIONS: Oral sodium phosphate solution was associated with a slight increase in serum creatinine, which was not clinically significant. Renal toxicity from OSPS appears to be minimal when used in patients with serum creatinine value <1.5 mg/dL.

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.

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.

Bronchopulmonary foregut malformation in association with diaphragmatic eventration.

Bronchopulmonary foregut malformations are uncommon anomalies, and their association with diaphragmatic eventration is rare. This report presents 2 cases with this association. Embryologically, a simultaneous disturbance in the development of pulmonary vessels and developing esophagotracheal septum may explain the etiopathogenesis of this association. Abnormal budding along the developing foregut tube may lead to foregut cysts. In both cases, the bronchopulmonary foregut malformations were excised, and the diaphragm was repaired. The results of surgery were gratifying in both cases.