Empirical planning target volume modeling for high precision MRI guided intracranial radiotherapy.

Purpose: Magnetic resonance image-guided radiotherapy for intracranial indications is a promising advance; however, uncertainties remain for both target localization after translation-only MR setup and intrafraction motion. This investigation quantified these uncertainties and developed a population-based planning target volume (PTV) model to explore target and organ-at-risk (OAR) volumetric coverage tradeoffs. Methods: Sixty-six patients, 49 with a primary brain tumor and 17 with a post-surgical resection cavity, treated on a 1.5T-based MR-linac across 1329 fractions were included. At each fraction, patients were setup by translation-only fusion of the online T1 MRI to the planning image. Each fusion was independently repeated offline accounting for rotations. The six degree-of-freedom difference between fusions was applied to transform the planning CTV at each fraction (CTVfx). A PTV model parameterized by volumetric CTVfx coverage, proportion of fractions, and proportion of patients was developed. Intrafraction motion was quantified in a 412 fraction subset as the fusion difference between post- and pre-irradiation T1 MRIs. Results: For the left-right/anterior-posterior/superior-inferior axes, mean ± SD of the rotational fusion differences were 0.1 ± 0.8/0.1 ± 0.8/-0.2 ± 0.9°. Covering 98 % of the CTVfx in 95 % of fractions in 95 % of patients required a 3 mm PTV margin. Margin reduction decreased PTV-OAR overlap; for example, the proportion of optic chiasm overlapped by the PTV was reduced up to 23.5 % by margin reduction from 4 mm to 3 mm. Conclusions: An evidence-based PTV model was developed for brain cancer patients treated on the MR-linac. Informed by this model, we have clinically adopted a 3 mm PTV margin for conventionally fractionated intracranial patients.

Significance of Age-Spleen-Platelet Ratio Index (ASPRI) to Exclude Cirrhosis in Patients with Chronic Hepatitis B.

Liver biopsy is an integral part of management of patients with Chronic Hepatitis B (CHB), which is helpful in confirming diagnosis, assessing grade of inflammation and stage of fibrosis and also in guiding treatment strategy. Although liver biopsy is relatively safe, morbidity occurs in 0.2-2% of patients. Hence various non-invasive markers, like AST-ALT Ratio (AAR), Age-Platelet Index (API), AST to Platelet Ratio Index (APRI), Fibroscan etc. have been developed worldwide to asses liver histology. Age-Spleen-Platelet Ratio Index (ASPRI) is new in this series. In this cross sectional study 51 (fifty one) patients with CHB, attending at Hepatology ward in Bangabandhu Sheikh Mujib Medical University, Dhaka, from January 2006 to May 2006, were studied. They were divided into two groups: Group I patients with ASPRI<5 and Group II patients with ASPRI>5. Clinical, serological, biochemical, virological parameters were analyzed and following liver biopsy, correlation of liver fibrosis with ASPRI was evaluated. Among 51 patients of CHB, 30 patients Group I with ASPRI<5 (mean 3.4) had mean fibrosis 1.3 using Knodell scoring system; while mean age, spleen size and platelet count were 23.2 years, 8.6cm and 278?109/L accordingly. In Group II, 21 patients with ASPRI>5 (mean 5.8) had mean fibrosis 1.8; mean age was 30.6 years, spleen size 9.5cm and platelet count 195?109/L. Mean liver fibrosis was significantly increased in Group II patients. In Group I patients, liver fibrosis showed significant correlation with platelet count (p=0.03) and ASPRI (p= 0.011), while none was observed in Group II patients. Age-Spleen-Platelet Ratio Index ASPRI can be used as a good tool for diagnosis of liver fibrosis in chronic hepatitis B. However, further study with larger study population is required to assess its validity.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

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.

Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

Increased survival of patients with end-stage hepatocellular carcinoma due to intake of ONCOXIN®, a dietary supplement.

BACKGROUND AND AIMS: Treatment and management of patients with end-stage hepatocellular carcinoma (HCC) represents a formidable challenge to contemporary branches of medical sciences. The study presented here was conducted to assess the utility of nutrient supplement, if any, for management of patients with end-stage HCC. MATERIALS AND METHODS: A total of 19 patients with end-stage HCC (Barcelona Clinic Liver Cancer [BCLC] staging D) were provided with ONCOXIN® for 3 months. Another 10 patients with end-stage HCC (BCLC stage D) with similar clinical conditions received conservative management, but they did not give consent for taking ONCOXIN® (non-ONCOXIN® group). All patients of both groups were followed on regular basis until their death. STATISTICAL ANALYSIS: The results were expressed as mean and standard deviation. Comparison between groups was performed using Student's t-test or the Mann-Whitney U test. For categorical data, Chi-square or Fisher exact test was applied. RESULTS: All patients of the control group (non-ONCOXIN® group) (10 of 10 patients) died within 2 months after study commencement. On the other hand, 10 of 19 patients receiving ONCOXIN® died within 2 months (less than 53% patients) after the start of taking ONCOXIN® (P < 0.05, compared with patients of non-ONCOXIN® group). Five more patients died within 5 months after the start of intake of ONCOXIN®. Four patients receiving ONCOXIN® survived for more than 6 months after study commencement. CONCLUSIONS: Although this is a preliminary report, it inspires considerable optimism about safety and efficacy of a food supplement for management of patients with end-stage HCC.

Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase.

Both consensus and controversy remains regarding surrogacy of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and alanine aminotransferase (ALT), however, these markers are used to ascertain the extent of liver damages and to guide therapeutic options in patients with chronic hepatitis B. However, little is known about liver histology of patients with chronic hepatitis B with undetectable HBV DNA and persistently normal ALT. Thirty-five incidentally-detected patients with chronic HBV infection (assessed by expression of hepatitis B surface antigen for more than 6 months) with undetectable HBV DNA and normal serum ALT were enrolled in this study. Liver biopsy specimens were taken from all patients and the extent of hepatic necroinflammation and liver fibrosis were evaluated. Moderate degree of hepatic necroinflammation was detected in 2 of 35 patients and severe hepatic fibrosis was seen in 6 of 35 patients. Two patients with undetectable HBV DNA and sustained normal ALT had moderate hepatic necroinflammation and severe hepatic fibrosis. In spite of undetectable HBV DNA for prolonged period and persistently normal ALT, some patients with chronic hepatitis B express evidences of progressive liver diseases. Large scale studies in different races and geographical regions should be accomplished to develop insights about management of these patients. Studies about extent of liver diseases in these patients should be accomplished in Treatment recommendation and management strategies should be developed for these patients.

Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh.

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh.

Hepatitis B among pregnant women attending health care facilities in rural Bangladesh.

This study assessed hepatitis B prevalence among pregnant women attending health care facilities in rural Bangladesh. Blood samples were collected from 480 participants. HBsAg was positive in 0.4% of subjects, anti-HBc was positive in 21.5% and anti-HBs was positive in 8.5% of subjects. HBsAg was more prevalent among the older age group. Hepatitis B has a low prevalence among pregnant women in rural Bangladesh. Existing hepatitis B vaccination schedule in the Expanded Program on Immunization (EPI) to vaccinate the children in rural Bangladesh is appropriate.

Combination therapy of lamivudine and interferon-alpha in pediatric patients with chronic hepatitis B in Bangladesh: a safe and effective therapeutic approach for pediatric CHB patients in developing countries.

Hepatitis B virus (HBV) is mainly transmitted during birth or perinatal period, however, treatment is not usually recommended for pediatric patients with chronic hepatitis B (CHB). Twelve pediatric patients with CHB in Bangladesh were treated with both lamivudine and interferon. Lamivudine was given at a dose of 3 mg/kg, daily for 12 months. Two months after commencement of lamivudine therapy, all patents were given interferon-alpha (3 million IU/square meter of body surface area) three times weekly, subcutaneously for 10 months. Combination therapy was safe for all pediatric CHB patients. The levels of serum HBV DNA became undetectable (less than 500 copies/ml) in 8 patients and reduced in 4 patients after the end of therapy. Anti-HBe was detected in 10 of 12 patients at this time point. The levels of serum alanine aminotransferase (ALT) were significantly reduced in these patients (p less than 0.05) due to therapy. Neither flare of HBV DNA nor elevation of serum ALT were detected during follow-up. In conclusion, combination therapy with lamivudine and interferon-alpha represents a new and novel therapeutic option for treatment of pediatric CHB patients.

Swine influenza (H1N1) pandemic: developing countries' perspective.

Since the first case of the current pandemic (H1N1) 2009 virus reported to WHO on 24 April 2009 on the American continent, the virus has spread in 160 countries and territories. By mid-2009, there were 135,000 cases and 816 deaths recorded. Pandemic preparedness is not advanced in most developing countries. Effective and essential measures include heightened surveillance, early detection and appropriate medical care. The use of local resources and capacity building with the assistance of developed nations will reduce the impact of this pandemic in the developing world.