Obstructive Jaundice with skin involvement - An unusual presentation of Myeloid Sarcoma.

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to leukemia, and obstructive jaundice in these patients usually presents late in the course of the disease. We present a rare case of a patient who presented with fever, jaundice, and pruritus with multiple nodular swellings in the left shoulder, left thigh, and lower back. Magnetic resonance cholangiopancreatography (MRCP) revealed periampullary mass lesion causing dilated common bile duct (CBD) and intrahepatic bile ducts; hence, endoscopic retrograde cholangiography with plastic stenting was done. Biopsy from the shoulder lesion revealed a mesenchymal tumor, and immunohistochemistry (IHC) confirmed the lesion as myeloid sarcoma. Myeloid sarcoma is an extramedullary tumor, a subtype of acute myeloid leukemia, and presentation as biliary lesions with multiple anatomical sites is very rare. The patient was started on chemotherapy after the normalization of bilirubin. The patient showed improvement of skin lesions and normalization of liver function test (LFT) after 3 weeks of chemotherapy.

Role of endoscopic ultrasound-guided tissue acquisition for the diagnosis of gastric wall thickening: a retrospective study with meta-analysis.

Background: Tissue acquisition from a thickened gastric wall using biopsy forceps may not always lead to diagnosis, given the submucosal location of the pathology. Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) may serve as a minimally invasive diagnostic tool in such cases. Hence, we aimed to assess the diagnostic outcome and safety of EUS-TA from thickened gastric walls. Methods: Data from patients with gastric wall thickening undergoing EUS-TA at 5 tertiary care centers from August 2020 to August 2022 were retrospectively analyzed. These data were pooled with studies obtained from a comprehensive search of Medline, Embase and Scopus from January 2000 to November 2022 and a meta-analysis was performed. Pooled event rates were calculated using an inverse variance model. Results: The search strategy yielded 13 studies that were combined with data from 30 patients from our centers; a total of 399 patients were included in the analysis. The pooled rate of sample adequacy was 94.1% (95% confidence interval [CI] 90.0-98.2), while the pooled rate of diagnostic accuracy was 91.3% (95%CI 87.0-95.5). The pooled sensitivity and specificity for diagnosing malignant lesions with EUS-TA from gastric wall thickening were 94.8% (95%CI 91.3-97.2) and 100% (95%CI 93.6-100), respectively. There were no reported adverse events in any of the studies. Conclusions: EUS-TA offers a safe and accurate diagnostic modality for the etiological diagnosis of thickened gastric walls. Further research is required to identify the needle type and optimal technique for improving outcomes.

Prevalence and predictors of functional evacuation disorder in patients with chronic constipation

Background: Functional evacuation disorder (FED) is the second most common cause of functional constipation (FC) after constipation-predominant irritable bowel syndrome. However, the data on FED is relatively scanty in our region. Hence, the present study was performed to evaluate the demographics of FED and to find out the predictors of FED in patients with chronic constipation. Methods: A total of 134 patients with chronic constipation diagnosed according to the Rome IV criteria who were referred for high-resolution anorectal manometry (HRAM) were retrospectively enrolled in the present study. All FC patients who underwent HRAM were asked to fill a questionnaire and underwent anorectal manometry and were submitted to the balloon expulsion test (BET). Results: The mean age of patients was 43.09 ± 9.32 years old, with a total of 76 (54%) males. The most common symptom was straining during defecation (87%) followed by incomplete evacuation (86%). The prevalence of FED, diagnosed by HRAM and by the BET was 39%. Patients with FED had a significantly higher percentage of straining and sensation of anorectal blockade compared with those without FED (96 versus 82%; p < 0.01; 81 versus 44%; p < 0.001, respectively). On the multivariate regression analysis, straining > 30 minutes (odds ratio [OR] = 3.63; p = 0.03), maximum squeeze pressure (OR = 1.05; p < 0.001), and balloon volume at maximal sensation (OR = 1.06; p < 0.001) were found to be significant independent predictors of FED. Conclusion: Prolonged straining and sensation of anorectal blockade were significant indicators of FED in patients with chronic constipation. (AU)

Tenofovir is Superior to Entecavir in Patients with Treatment-naïve Hepatitis B e-Antigen-Positive Chronic Hepatitis B.

BACKGROUND AND AIM: Chronic Hepatitis B (CHB) is a global health problem affecting around 400 million of people worldwide. Two available first-line antiviral drugs are tenofovir disoproxil fumarate (TDF) and Entecavir (ETV). Till date,there are few published reports from India comparing efficacy of TDF and ETV in CHB cases. Therefore, this present study was carried out with an aim to compare the efficacy of ETV and TDF in patients with nucleos(t)ide naïve CHB. MATERIALS AND METHODS: This retrospective cohort study was carried out in 192 treatment naïve CHB cases, who completed 24 months of treatment with either TDF or ETV between March 2015 and August 2017. The primary end point of the study was undetectable hepatitis B virus DNA after 24 months of therapy. RESULTS: Of total 192 patients with CHB, 38 hepatitis B e-antigen (HBeAg)-positive and 53 HBeAg-negative patients were treated with tenofovir, whereas 40 HBeAg-positive and 61 HBeAg-negative patients were treated with ETV. Pretreatment characteristics at baseline were not statistically different between the TDF and ETV groups. Patients treated with TDF achieved significantly higher complete viral suppression as compared with ETV-treated patients (Log rank: 7.04, P = 0.008) in HBeAg-positive CHB during the 24 months follow-up time; whereas no significant difference in viral suppression rate could be noticed in HBeAg-negative patients (Log rank: 0.98, P = 0.38). Both univariate and multivariate analysis by cox proportional hazard model confirmed that tenofovir had significant rate of complete viral suppression in comparison with ETV in HBeAg-positive patients (P < 0.05); whereas complete viral suppression rates were similar in HBeAg-negative patients. CONCLUSION: In our study, tenofovir had more effective antiviral suppressive effect compared with ETV in HBeAg-positive, nucleos(t)ide-naïve CHB cases.

Fatty changes associated with N-Nitrosodiethylamine (DEN) induced hepatocellular carcinoma: a role of sonic hedgehog signaling pathway.

BACKGROUNDS AND AIMS: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality across the world. Non-viral etiological factors including obesity and metabolic syndrome have now become prevalent cause of hepatocellular carcinoma. Sonic Hedgehog (SHH) pathway is activated in hepatocellular carcinoma but its role in regulation of lipogenic molecules during the hepatocarcinogenesis is not known. The aim of present study is to explore the role of SHH pathway in fatty changes associated with hepatocarcinogenesis at different stages and to further correlate the expression of SHH with lipogenic pathways. RESULTS: Our results demonstrated significant increase in lipidosis and fibrosis in DEN+CCl4 treated animals. It was simultaneously associated with the enhanced expression level of SHH, E2F1, adiponectin, and lipogenic molecules in DEN+CCl4 treated animals. These results were also corroborated with the similar findings in higher stage patients' biospecimens. METHODS: N-Nitrosodiethylamine (DEN) and Carbon TetraChloride (CCl4) induced hepatocellular acrcinoma model in male Wistar rats were established to study the expression level of SHH pathway and associated fatty changes during different stages of hepatocarcinogenesis. The expression levels of SHH, E2F1, and lipogenic molecules were checked at different stages of hepatocellular carcinoma. These results were further compared with biospecimens of hepatocellular carcinoma patients of different stages. CONCLUSIONS: Our results revealed an unknown aspect of SHH pathway in hepatocarcinogenesis via its control over lipogenesis. It gives insight into the lipogenic properties of DEN+CCl4 induced rodent hepatocarcinogenesis model and how SHH pathway operate to arbitrate this response.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Anti-hepatitis B virus (HBV) response of imiquimod based toll like receptor 7 ligand in hbv-positive human hepatocelluar carcinoma cell line.

BACKGROUND: Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. METHODS: The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837. Cell cycle analysis was performed using flow-cytometry. Expression of TLR7 and chief cell cycle regulator governing G1/S transition, p53 was also seen in liver biopsysss samples of CHB patients. HBV induced alteration in histone modifications in HepG2 cells and its restoration on TLR7 activation was determined using western blot. RESULTS: The TLR7 expression remains downregulated in HepG2.2.15 cells and in liver biopsy samples from CHB patients. Interestingly HBV DNA viral load showed an inverse relationship with the TLR7 expression in the biopsy samples. We also evaluated the anti-viral activity of R837, an agonist of TLR7. It was observed that there was a suppression of HBV replication and viral protein production upon TLR7 stimulation. R837 triggers the anti-viral action probably through the Jun N-terminal Kinase (JNK) pathway. We also observed a downregulation of histone H3K9Me3 repression mark upon R837 treatment in HBV replicating HepG2.2.15 cells, mimicking that of un-infected HepG2 cells. Additionally, the G1/S cell cycle arrest introduced by HBV in HepG2.2.15 cells was released upon ligand treatment. CONCLUSION: The study thus holds a close insight into the changes in hepatocyte micro-environment on TLR7 stimulation in HBV infection.

A 10-year-old child presenting with syndromic paucity of bile ducts (Alagille syndrome): a case report.

BACKGROUND: Alagille syndrome, a rare genetic disorder with autosomal dominant transmission, manifests with five major features: paucity of interlobular bile ducts, characteristic facies, posterior embryotoxon, vertebral defects, and peripheral pulmonary stenosis. Globally, only 500 cases have so far been reported, with only five cases reported in the Indian subcontinent. Rarely, Alagille syndrome also presents with skin manifestations and early-onset chronic liver disease, which was found in our case. We believe that we report what could be the first case of Alagille syndrome presenting with café au lait spots, as no such published case report could be found in the literature. CASE PRESENTATION: We report an unusual case of childhood cholestatic jaundice with neonatal onset of jaundice. A 10-year-old boy from the Indian subcontinent presented with obstructive jaundice from early infancy. He also had recurrent fractures of his upper limb bones, intermittent bleeding from his nose, productive cough, decreased night vision, hyperpigmented spots over his skin, and progressive enlargement of his abdomen. Histological examination of a liver biopsy specimen revealed a paucity of bile ducts and changes suggestive of chronic liver disease. Our patient was diagnosed with Alagille syndrome and managed conservatively but died 1 year after the final diagnosis. CONCLUSIONS: This particular syndromic form of paucity of bile duct disorder has been rarely reported in the Indian literature so far. Our case is notable because the child had café au lait spots and very early onset of chronic liver disease, which is quite rare in Alagille syndrome. We believe this to be the first case report on Alagille syndrome manifesting with café au lait syndrome and such early onset of chronic liver disease.

Socioeconomic impact of alcohol in patients with alcoholic liver disease in eastern India.

AIM: The aim of this study is to estimate the socioeconomic impact of alcohol use on patients with alcoholic liver disease (ALD) and their families. METHODS: The demographic and socioeconomic data were collected from hospitalized ALD patients and attendants using a self designed non validated questionnaire and analyzed. RESULTS: Study subjects included 100 consecutive ALD patients (all males). Sixty percent were between 30 and 50 years. Most were married (96 %), literate (63 %), either businessmen (37 %) or employed (30 %) and belonged to middle socioeconomic class. Ninety percent started alcohol use before age 30 years and half during teenage. Mean alcohol intake was 190 mL/day (mean duration 23 years); 60 % consumed alcohol daily. Concomitant tobacco abuse was noted in 79 %. Average expenditure on alcohol was Rs 3800/month. Average hospitalizations for ALD related problems was 2.6 times/year with average expenditure of INR 30,000 (~440 US$) during each hospitalization. For treatment expenses, 86 % of patients borrowed money from friends/relatives, 36 % used saving deposits, and 4 % sold personal belongings. Eleven percent lost their job, and 7 % sold immovable property. In 43 % of cases, children were deprived of education. Besides, 52 % had disturbed social and family life, 34 % abused their spouse, 20 % suffered accidents, and 37 % indulged in physical violence. CONCLUSION: Majority of ALD patients and their families had disturbed social and family life and incurred severe financial loss arising of alcohol use.

Anti-viral role of toll like receptor 4 in hepatitis B virus infection: An in vitro study.

AIM: Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4 (TLR4) in hepatitis B virus (HBV) infection. METHODS: Real time PCR was used to analyze the transcription of TLR4 signaling molecules, cell cycle regulators and HBV DNA viral load after triggering the HepG2.2.15 cells with TLR4 specific ligand. Nuclear factor (NF)-κB translocation on TLR4 activation was analyzed using microscopic techniques. Protein and cell cycle analysis was done using Western Blot and FACS respectively. RESULTS: The present study shows that TLR4 activation represses HBV infection. As a result of HBV suppression, there are several changes in host factors which include partial release in G1/S cell cycle arrest and changes in host epigenetic marks. Finally, it was observed that anti-viral action of TLR4 takes place through the NF-κB pathway. CONCLUSION: The study shows that TLR4 activation in HBV infection brings about changes in hepatocyte microenvironment and can be used for developing a promising therapeutic target in future.