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Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Background Systemic inflammatory response syndrome (SIRS) is associated with an increased risk of hepatic encephalopathy, renal failure, and poor outcome in patients with cirrhosis; however, there is a paucity of studies on this entity for severe alcoholic hepatitis (SAH). Aim To evaluate SIRS at baseline as a predictor of development of acute kidney injury (AKI) and mortality in patients with SAH. Methods Consecutive in-patients with SAH (discriminant function ≥ 32) without AKI at baseline were followed up for the development and progression of AKI (AKIN criteria). Results Of the 365 patients (mean age 45.5 ± 9.5, 356 males), SIRS at baseline was present in 236 (64.6 %). AKI developed in 122 (33.4 %), of which 50 (40.9 %) had progression of AKI. SIRS was associated with bacterial infections in 96 (40.6 %) and in 140 (59.3 %) occurred in the absence of proven infection microbiologically. The presence of SIRS predicted both AKI development ( p  < 0.001, OR 2.9, 95 % CI 1.7–4.8) and AKI progression ( p  = 0.002, OR 3.27, 95 % CI 1.48–7.21). Resolution of AKI also had a significant inverse association with SIRS ( p  = 0.001). High MELD score ( p  = 0.002, HR 1.1, 95 % CI 1.02–1.09), in-hospital progression of AKI ( p  = 0.04, HR 1.54, 95 % CI 1.003–2.38), and SIRS ( p  = 0.004, HR 1.98, 95 % CI 1.25–3.1) were significant predictors of 90-day mortality (model 1), while high MELD score ( p  < 0.001, HR 1.1, 95 % CI 1.04–1.12) and bacterial infections ( p  = 0.001, HR 1.8, 95 % CI 1.27–2.6) were independent predictors of mortality in the second multivariate model (model 2). Conclusion SIRS at admission predicts both the development of AKI and 90-day mortality in patients with SAH. This could definitely have a therapeutic and prognostic implication.

Bone marrow stem cells (BM-SCs) and their progeny play a central role in tissue repair and regeneration. In patients with chronic liver failure, bone marrow (BM) reserve is severally compromised and they showed marked defects in the resolution of injury and infection, leading to liver failure and the onset of decompensation. Whether BM failure is the cause or consequence of liver failure during cirrhosis is not known. In this study, we aimed to determine the underlying relationship between BM failure and regeneration failure in cirrhosis. C57Bl/6(J) mice were used to develop chronic liver injury through intra-peritoneal administration of carbon tetrachloride (CCl4) for 15 weeks (0.1-0.5 ml/kg). Animals were sacrificed to study the transition of cirrhosis and BM defects. To restore the BM-SC reserve; healthy BM cells were infused via intra-BM infusion and assessed for changes in liver injury, regeneration, and BM-SC reserve. Using a CCl4-induced animal - model of cirrhosis, we showed the loss of BM-SCs reserve occurred before regeneration failure and the onset of non-acute decompensation. Intra-BM infusion of healthy BM cells induced the repopulation of native hematopoietic stem cells (HSCs) in cirrhotic BM. Restoring BM-HSCs reserve augments liver macrophage-mediated clearance of infection and inflammation dampens neutrophil-mediated inflammation, accelerates fibrosis regression, enhances hepatocyte proliferation, and delays the onset of non-acute decompensation. These findings suggest that loss of BM-HSCs reserve underlies the compromised innate immune function of the liver, drives regeneration failure, and the onset of non-acute decompensation. We further provide the proof-of-concept that rejuvenating BM-HSC reserve can serve as a potential therapeutic approach for preventing regeneration failure and transition to decompensated cirrhosis.

Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay. A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001). Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

Problems of search optimization in a discrete space, particularly, in a binary space where a variable can take only two values, are of great practical importance. This paper proposes a new population-based discrete optimization algorithm that uses probability distributions of variables. The distributions determine the probability of taking one or another discrete value and are generated by transforming target values of solutions into their weight coefficients. The performance of the algorithm is evaluated using unimodal and multimodal test functions with binary variables. The experimental results demonstrate the high efficiency of the proposed algorithm in terms of convergence rate and stability.

Metastasis-associated protein 1 (MTA1), a master chromatin modifier, has been shown to regulate cancer progression and is widely upregulated in human cancer, including hepatitis B virus-associated hepatocellular carcinomas (HCCs). Here we provide evidence that hepatitis B virus transactivator protein HBx stimulates the expression of MTA1 but not of MTA2 or MTA3. The underlying mechanism of HBx stimulation of MTA1 involves HBx targeting of transcription factor nuclear factor (NF)-κB and the recruitment of HBx/p65 complex to the NF-κB consensus motif on the relaxed MTA1 gene chromatin. We also discovered that MTA1 depletion in HBx-expressing cells severely impairs the ability of HBx to stimulate NF-κB signaling and the expression of target proinflammatory molecules. Furthermore, the presence of HBx in HBx-infected HCCs correlated well with increased MTA1 and NF-κB-p65. Collectively, these findings revealed a previously unrecognized integral role of MTA1 in HBx stimulation of NF-κB signaling and consequently, the expression of NF-κB targets gene products with functions in inflammation and tumorigenesis.

The hepatic venous pressure gradient (HVPG) clearly reflects portal pressure in cirrhotic portal hypertension. Its relation with variceal bleeding has been well studied. We undertook to study the relation of HVPG to variceal size, Child's status, and etiology of cirrhosis. Patients with cirrhotic portal hypertension with esophageal varices underwent HVPG measurement as part of a prospective evaluation. One hundred seventy-six cirrhotics with varices (M:F, 140:36; mean age, 42.6 +/- 13.4 years), 104 with CLD related to viral etiology, 40 with alcoholic liver disease, 26 cryptogenic with cirrhosis, and 6 with miscellaneous causes of CLD underwent HVPG measurement. The mean HVPG was lower in patients with small varices (n = 77; 14.6 +/- 5.9 mm Hg) than in patients with large varices (n = 99; 19.2 +/- 6.6 mm Hg; P < 0.01). In patients with large varices, the mean HVPG in bleeders (n = 37) was higher than in nonbleeders (n = 62) (21.7 +/- 7.2 vs 17.9 +/- 6.2 mm Hg; P < 0.01). The mean HVPG was significantly higher in Child's B (n = 97; 17.4 +/- 6.9 mm Hg) and C (n = 56; 19.0 +/- 5.7 mm Hg) compared to Child's A cirrhotics (n = 23; 12.2 +/- 5.9 mm Hg; P < 0.01), and Child's C compared to Child's B cirrhotics (P = 0.05). HVPG was higher in alcoholic compared to nonalcoholic cirrhotics (20.8 +/- 7.3 vs 16.4 +/- 6.3 mm Hg; P < 0.05), but this was not significant in multivariate analysis. The HVPG was comparable between hepatitis B- and hepatitis C virus-related cirrhotics (P = 0.8). Cirrhotics with ascites had a higher HVPG than those without ascites (18.5 +/- 5.6 vs 16.6 +/- 7.6 mm Hg; P = 0.02). In multivariate analysis, only Child's status, size of varices, and variceal bleed predicted higher HVPG. HVPG is higher in cirrhotics with large varices and a history of bleed. There is a good correlation between HVPG and large varices, bleeder status, and ascites. A higher HVPG reflects more severe liver disease. The etiology of liver disease did not influence the portal pressure.

Abstract Renal cell cancinoma (RCC) is a unique malignancy with features of late recurrences, metastasis to any organ, and frequent association with second malignancy. It most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain although metastases can occur anywhere. RCC metastatic to the duodenum is especially rare, with only few cases reported in the literature. Herein, we review literature of all the reported cases of solitary duodenal metastasis from RCC and cases of neuroendocrine tumor (NET) as synchronous/metachronous malignancy with RCC. Along with this, we have described a unique case of an 84-year-old man who had recurrence of RCC as solitary duodenal metastasis after 37 years of radical nephrectomy and metachronous pancreatic NET.

Bleeding from esophageal varices is associated with mortality rates ranging from 30 to 70 percent. 1 , 2 Many therapies have been evaluated for primary prophylaxis against bleeding in people with cirrhosis and large varices. 3 – 5 The most effective therapy is the use of nonselective beta-blockers, which reduce the incidence of a first bleeding episode and, to some extent, reduce bleeding-related mortality. 5 , 6 However, beta-blockers have unpredictable effects on the hepatic venous pressure gradient, which is used to assess their efficacy. 7 , 8 Measurement of this gradient requires an invasive technique in which a catheter is passed through the femoral or jugular vein . . .

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.