Management of occult hepatitis B virus infection:An update for the clinician

Occult hepatitis B virus(HBV) infection(OBI) is defined by the presence of HBV DNA in the liver tissue of individuals who test negative for hepatitis B surface antigen(HBsAg).Patients who have recovered from acute hepatitis B can carry HBV genomes for a long time and show histological patterns of mild necro-inflammation,even fibrosis,years after the resolution of acute hepatitis,without showing any clinical or biochemical evidence of liver disease.At least in conditions of immunocompetence,OBI is inoffensive itself,but when other relevant causes of liver damage are present it might make the course of the liver disease worse.The risk of HBV transmission through transfusion is related to blood donations negative for HBsAg that have been collected during the pre-seroconversion period or during chronic OBI.Use of HBV nucleic acid amplification testing and multivalent anti-HBs antibodies in the HBsAg assays is recommended for detection of true and false OBI,respectively.It is not known if prior hepatitis B immunization with an optimal anti-HBs response in cases of HBV transmission through organ transplantation can effectively modulate or abort the infection.Use of anti-viral agents as prophylaxis in patients with serological evidence of past HBV infection prevents reactivation of OBI after transplantation in most cases.Reactivation of OBI has been observed in other conditions that cause immunosuppression,in which antiviral therapy could be delayed until the HBV DNA or HBsAg becomes detectable.OBI might contribute to the progression of liver fibrosis and hepatocellular carcinoma development in patients with chronic liver disease.

Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases

Bacterial translocation(BT) has been impeccably implicated as a driving factor in the pathogenesis of a spectrum of chronic liver diseases(CLD). Scientific evidence accumulated over the last four decades has implied that the disease pathologies in CLD and BT are connected as a loop in the gut-liver axis and exacerbate each other. Pregnane X receptor(PXR) is a ligandactivated transcription factor and nuclear receptor that is expressed ubiquitously along the gut-liver-axis. PXR has been intricately associated with the regulation of various mechanisms attributed in causing BT. The importance of PXR as the mechanistic linker molecule in the gutliver axis and its role in regulating bacterial interactions with the host in CLD has not been explored. Pub Med was used to perform an extensive literature search using the keywords PXR and bacterial translocation, PXR and chronic liver disease including cirrhosis. In an adequate expression state, PXR acts as a sensor for bile acid dysregulation and bacterial derived metabolites, and in response shapes the immune profile beneficial to the host. Activation of PXR could be therapeutic in CLD as it counter-regulates endotoxin mediated inflammation and maintains the integrity of intestinal epithelium. This review mainly focuses PXR function and its regulation in BT in the context of chronic liver diseases.

Malnutrition negatively impacts the quality of life of patients with cirrhosis: An observational study

AIM To verify how malnutrition is related to health-related quality of life(HRQL) impairment in patients with cirrhosis.METHODS Data was retrospectively abstracted from medical records and obtained by direct interview. We included patients with cirrhosis from any etiology, evaluated at the Liver Clinic from Gastroenterology Department in a tertiary healthcare center, from June 2014 to June 2016. Child-Pugh score, data about complications, and demographic, clinical and anthropometric characteristics of patients were obtained. Nutritional status was evaluated by the Subjective Global Assessment(SGA). HRQL was evaluated through the Chronic Liver Disease Questionnaire. Patients were requested to assess their global HRQL with the following code: 0 = impairment of HRQL, when it was compared with other healthy subjects; 1 = good HRQL, if it was similar to the quality of life of other healthy subjects. To compare the primary outcome between malnourished and well-nourished groups, the χ~2 test, Fisher's exact test or Student's t-test were used, based on the variable type. Associations between predictor variables and deterioration of HRQL were determined by calculating the hazard ratio and 95% confidence interval using Cox proportional hazards regression. RESULTS A total of 127 patients with cirrhosis were included, and the mean age was 54.1 ± 12.3 years-old. According to Child-Pugh scoring, 25(19.7%) were classified as A(compensated), 76(59.8%) as B, and 26(20.5%) as C(B/C = decompensated). According to SGA, 58(45.7%) patients were classified as well-nourished. Sixty-nine patients identified HRQL as good, and 76 patients(59.8%) perceived impairment of their HRQL. Multivariate analysis to determine associations between predictor variables and self-perception of an impairment of HRQL found strong association with malnutrition(P < 0.0001). The most important impaired characteristics in malnourished patients were: Presence of body pain, dyspnea on exertion with daily activities, decreased appetite, generalized weakness, trouble lifting or carrying heavy objects, and decreased level of energy(P < 0.0001).CONCLUSION Malnutrition is a key factor related to impairment of HRQL in patients with cirrhosis.

Evolving strategies for liver fibrosis staging: Non-invasive assessment

Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either noninvasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change- even in the event of fibrosis regression. Therefore, future studies are needed to validate noninvasive methods in predicting the different phases of liver cirrhosis.

Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis:A prospective study

AIM To assess the vitamin D(VD) deficiency as a prognostic factor and effect of replenishment of VD on mortality in decompensated cirrhosis. METHODS Patients with decompensated liver cirrhosis were screened for serum VD levels. A total of 101 VD deficient patients(< 20 ng/mL) were randomly enrolled in two groups: Treatment group(n = 51) and control group(n = 50). Treatment group received VD treatment in the form of intramuscular cholecalciferol 300000 IU as loading dose and 800 IU/d oral as maintenance dose along with 1000 mg oral calcium supplementation. The VD level, clinical parameters and survival of both the groups were compared for 6-mo.RESULTS Prevalence of vitamin D deficiency(VDD) in decompensated CLD was 84.31%. The mean(SD) age of the patients in the treatment group(M:F: 40:11) and control group(M:F: 37:13) were 46.2(± 14.93) years and 43.28(± 12.53) years, respectively. Baseline mean(CI) VD(ng/mL) in control group and treatment group were 9.15(8.35-9.94) and 9.65(8.63-10.7), respectively. Mean(CI) serum VD level(ng/mL) at 6-mo in control group and treatment group were 9.02(6.88-11.17) and 29(23-35), respectively. Over the period of time the VD, calcium and phosphorus level was improved in treatment group compared to control group. There was nonsignificant trend seen in greater survival(69% vs 64%; P > 0.05) and longer survival(155 d vs 141 d; P > 0.05) in treatment group compared to control group. VD level had no significant association with mortality(P > 0.05). In multivariate analysis, treatment with VD supplement was found significantly(P < 0.05; adjusted hazard ratio: 0.48) associated with survival of the patients over 6-mo. CONCLUSION VD deficiency is very common in patients of decompensated CLD. Replenishment of VD may improve survival in patients with decompensated liver cirrhosis.

Chronic liver disease is universal in children with biliary atresia living with native liver

AIM To examine the medical status of children with biliary atresia(BA) surviving with native livers.METHODS In this cross-sectional review,data collected included complications of chronic liver disease(CLD)(cholangitis in the preceding 12 mo,portal hypertension,variceal bleeding,fractures,hepatopulmonary syndrome,portopulmonary hypertension) and laboratory indices(white cell and platelet counts,total bilirubin,albumin,international normalized ratio,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transpeptidase). Ideal medical outcome was defined as absence of clinical evidence of CLD or abnormal laboratory indices. RESULTS Fifty-two children [females = 32,62%; median age 7.4 years,n = 35(67%) older than 5 years] with BA(median age at surgery 60 d,range of 30 to 148 d) survived with native liver. Common complications of CLD noted were portal hypertension(40%,n = 21; 2 younger than 5 years),cholangitis(36%) and bleeding varices(25%,n = 13; 1 younger than 5 years). Fifteen(29%) had no clinical complications of CLD and three(6%) had normal laboratory indices. Ideal medical outcome was only seen in 1 patient(2%). CONCLUSION Clinical or laboratory evidence of CLD are present in 98% of children with BA living with native livers after hepatoportoenterostomy. Portal hypertension and variceal bleeding may be seen in children younger than 5 years of age,underscoring the importance of medical surveillance for complications of BA starting at a young age.

Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver disease

AIM To investigate the relationship between 25-hydroxyvitamin D(25-OHD) deficiency and hepatic encephalopathy(HE) in patients with chronic liver disease(CLD).METHODS A retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHDmeasurement were excluded from the analysis. RESULTS One hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic(P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease(r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE(P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE(OHE) at a significantly lower model for end stage liver disease(MELD) score than individuals without OHE(P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38.CONCLUSION25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.