Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors.

Hepatitis E virus (HEV) usually causes self-limiting acute hepatitis, but the disease can become chronic in immunocompromised individuals. HEV infection in pregnant women is reported to cause up to 30% mortality, especially in the third trimester. Additionally, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection. The mechanism of HEV pathogenesis remains poorly understood. Innate immunity is the first line of defense triggered within minutes to hours after the first pathogenic insult. Growing evidence based on reverse genetics systems, in vitro cell culture models, and representative studies in animal models including non-human primates, has implicated the role of the host's innate immune response during HEV infection. HEV persists in presence of interferons (IFNs) plausibly by evading cellular antiviral defense. This review summarizes our current understanding of recognizing HEV-associated molecular patterns by host cell Pattern Recognition Receptors (PRRs) in eliciting innate immune response during HEV infection as well as mechanisms of virus-mediated immune evasion.

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

INTRODUCTION: Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. METHODS: The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. RESULTS: Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. CONCLUSION: Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

Pancreatico-pleural and bronchial fistulae and associated pseudocysts: case series.

CONTEXT: Pancreatico-pleural fistula is rare complication of chronic or acute pancreatitis. Previous studies have reported imaging features and various management options of this condition including conservative/medical management, endoscopic treatments and surgery.This article reviews the myriad of imaging appearances of this condition in multimodality imaging and different strategies for the successful management in a short case series. METHODS: After obtaining the institutional ethics committee approval, retrospective review of the medical records of five patients of pancreatico-pleural fistulae who were diagnosed and successfully managed in our hospital in 2012 and 2013 was done. Follow up with out patient records of these patients was also included.Findings were compared with the current available literature on this entity. RESULTS AND DISCUSSION: Pancreatico-pleural fistulae presents with massive pleural effusion.A high index of suspicion is essential for accurate diagnosis. Demonstration of the fistulous tracts requires cross sectional imaging with contrast enhanced CT being most commonly used and affords accurate diagnosis. MRI demonstrates the tracts and ductal disruptions with greater detail and are helpful in confirming the CT findings. Endoscopic ultrasound and ERCP also offer potential of diagnosis, although being technically demanding and invasive is reserved for interventions. Management of these conditions should be initially conservative with endoscopic stenting being offered in selected cases with favourable anatomy and not responding to conservative management. Surgery is reserved for cases not responding to conservative and endoscopic management. CONCLUSION: In conclusion this case series highlights the clinical and imaging spectrum of pancreatico-pleural fistulae and provides insight into the different management strategies that can be adopted for this condition.

Role of Endoscopic Ultrasound in the Management of Pancreatic Cancer.

Pancreatic cancer is one of the common causes of cancer-associated mortality with a dismal overall prognosis which has remained virtually unchanged over decades. In the present era, the management of patients with pancreatic cancer involves a multi-disciplinary team of radiologists, gastroenterologists, surgical oncologists, medical oncologists, radiation oncologists and other specialists. The advancement of interventional endoscopy has made a significant impact in the management of pancreatic cancers. Since the inception of endoscopic ultrasound, it has evolved over the last few decades in the management of pancreatic malignancies and its role in staging and tissue acquisition is well established. There is an emerging role of endoscopic ultrasound in the treatment and palliation of unresectable pancreatic cancer. The aim of this article is to review the role of endoscopic ultrasound in diagnostic and therapeutic interventions in the current era.

Biomarker in Hepatocellular Carcinoma.

Liver cancer is one of the most prevalent types of cancer and a major contributor to the socioeconomic burden worldwide. The pathogenesis of hepatocellular carcinoma (HCC) is contributed by various etiological factors like virus infection, excessive alcohol consumption, exposure to toxins, or metabolic disorders. Majority of patients are diagnosed with late-stage HCC, which restricts its management to only palliative care. HCC, if diagnosed early, increases the survival and quality of life. Currently available biomarker (alpha-fetoproteins) have several limitations, that impede the early diagnosis and staging of cancer. This warrants the continous search in pursuit of a novel biomarker. Several research works in diverse areas have contributed to the identification of various novel biomarkers that have shown multifaceted application in early disease diagnosis, which further aid in targeted and effective therapy that can prevent cancer progression. This improves the overall health status of the patient along with significant reduction in caretaker's burden. With the aid of novel technologies, several biomarkers have been investigated and validated in mutliple preliminary research works. Therefore in this review, we have outlined various novel biomarkers that showed promising outcomes in their trials and we have highlighted the developing areas that act as game changers in cancer diagnosis and management.

Health-related Quality of Life in Patients With Liver Cirrhosis: A Randomized Study.

Background/Aims: Health-related quality of life (HRQoL) relates to how people perceive illness and treatment affects their physical health, emotional health, functional status, and social position. Along with clinical goals, HRQoL is significant. Therefore, the present study evaluates the effect of patient counseling and education on HRQoL of cirrhotic patients. Methods: This prospective study was conducted in a tertiary care center of coastal Karnataka, Kasturba Medical College, Manipal, Karnataka from October 2022 with a three-month follow-up. Patients with a confirmed diagnosis of liver cirrhosis visiting the outpatient department of age ≥18 were enrolled in the study and divided on the basis of compensated and decompensated cirrhosis. Patients were randomized into two groups i.e., case and control in compensated and decompensated group through the envelop method of randomization. The case group received patient education and counseling along with standard medical therapy. CLDQ was used to evaluate HRQoL scores on baseline and after the third month. Results: A total of 104 patients were enrolled with a mean age of 53.49 ± 11.25, with most being male (80.7%). Out of 104, 60 and 44 had compensated and decompensated cirrhosis. Case and control groups did not differ significantly on baseline. However, on follow-up, the compensated group showed significant improvement in abdominal symptoms, fatigue, and emotional functions. Meanwhile, the decompensated group showed significant improvement in activity, emotional function, and worry domain of CLDQ. Higher MELD scores were the significant factor associated with lower HRQoL scores. Conclusion: Patient education and counseling positively impacted the fatigue, emotional, and worry domain of the CLDQ. Hence, the present study recommends making an effort to promote patient counseling and education via leaflets or videos.

Factors Affecting and Promoting Health-related Quality of Life in Patients With Liver Cirrhosis: An Underestimated Domain in Patient Care.

Cirrhosis patients have poor health-related quality of life (HRQoL). To enhance medical care and therapeutic approaches, it is crucial to identify factors that alter HRQoL in patients with cirrhosis. The present study aims to identify the potential factors affecting and promoting HRQoL in patients with liver cirrhosis. Four databases were extensively searched, including PubMed, Scopus, Embase, and Google Scholar. All original articles with liver cirrhosis and factor-altering HRQoL were included. The present study showed that elderly age, female gender, low family income, low body mass index (BMI), presence of anxiety and depression, presence of cirrhosis complications including ascites, hepatic encephalopathy (HE), and abnormal endoscopic findings, high disease severity score, presence of sarcopenia, disturbed sleep pattern, muscle cramps, poor sexual health, and increased levels of bilirubin, prothrombin time, and albumin-bilirubin ratio were the significant factors associated with lower HRQoL scores. Meanwhile, physical exercise, liver transplant, stem cell therapy, mindfulness, and the use of probiotics, rifaximin, and lactulose were associated with increased HRQoL scores. The present study recommends more prospective or randomized control trials with interventions including health education, yoga, psychotherapy, and other potential factors promoting HRQoL in patients with liver cirrhosis. The present study also emphasizes that the treating physician should consider taking HRQoL into account when prescribing medical therapy.

Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients.

INTRODUCTION: Acute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients. METHODOLOGY: In the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis. RESULTS: Of 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001). CONCLUSION: AKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Role of granulocyte colony stimulating factor in the treatment of cirrhosis of liver: a systematic review.

OBJECTIVE: We performed a systematic review to analyze the benefits of and risk factors associated with granulocyte colony stimulating factor (GCSF) in patients with liver cirrhosis. METHODS: PubMed, Scopus, and Embase were searched for randomized controlled trials and case-control studies that compared the use of GCSF with another treatment or control group. The Jadad and Newcastle-Ottawa scales were used to assess the risk of bias in the included studies. The primary outcome studied was mortality; and the secondary outcomes were the disease severity score, liver transplantation criteria, complications, CD34+ cell count, adverse events, and health-related quality of life (HRQOL). PROSPERO registration number CRD42023416014. RESULTS: The initial search yielded 2,235 studies, of which seven studies of 670 patients with liver cirrhosis were included. Multiple cycles of GCSF significantly improved the survival rate, disease severity score, CD34+ cell count, and HRQOL; and significantly reduced the incidences of liver transplantation, ascites, infection, and hepatic encephalopathy. Fatigue and backache were the most commonly reported adverse events. CONCLUSION: GCSF significantly improves the survival rate and disease severity scores, and reduces the incidence of complications in patients with liver cirrhosis. The administration of GCSF is likely to be effective in patients awaiting liver transplantation.

Exosomes in chronic liver disease.

Chronic liver disease (CLD) is the major cause of mortality and morbidity, particularly in developing countries. Although there has been a significant advancement in the identification and treatment of liver diseases over time, clinical results are not satisfactory in advanced liver disease. Thus, it is crucial to develop certain technology for early detection, and curative therapies and to investigate the molecular mechanisms behind CLD's pathogenesis. The study of exosomes in CLD is a rapidly developing field. They are structurally membrane-derived nano vesicles released by various cells. In CLD, exosomes released from injured hepatic cells affect intercellular communication, creating a microenvironment conducive to the illness's development. They also carry liver cell-specific proteins and miRNAs, which can be used as diagnostic biomarkers and treatment targets for various liver diseases. End-stage liver disease can only be treated by a liver transplant, however, the low availability of compatible organs, high expenses of treatment, and surgical complications significantly lower patient survival rates. Early diagnosis and therapeutic intervention of CLD positively affect the likelihood of curative treatment and high patient survival rates. Considering the possibility that exosomes could be employed as tools for disease diagnostics and clinical intervention, The current study briefly summarizes the roles of exosomes and their cargo in diagnosing and treating liver diseases.

Indigenous technique to develop sponge for endo vaccum therapy in post-operative anastomotic leak: A case report.

Oesophageal anastomotic leaks are serious complications with high mortality (20-50%)1 especially in the post-operative setting of malignant disease. They occur in 5-30% of cases,1 usually presenting with severe mediastinal sepsis. Revision surgery has been replaced by the use of endoscopic stents, clips, glue and vacuum therapy. The latter is the simplest and least liable to further complication. As an endo sponge was not commercially available, we introduced a self-made bed-side endo sponge, with evident success.

Thiopurine therapy in inflammatory bowel disease in the pandemic era: Safe or unsafe?

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Crohn's disease (CD) and Ulcerative colitis (UC) are the two major types affecting millions across the globe. Various immunomodulatory drugs consisting of small molecules (thiopurines, methotrexate and tofacitinib) and biologics are used to treat IBD. Thiopurines (TP) are widely used in the treatment of IBD and it plays an important role both alone and in combination with anti-TNF agents as IBD maintenance therapy. Although the advent of biologics therapy has significantly advanced the management of IBD, TP remains the mainstay of treatment in resource-limited and low economic settings. However, the recently commenced pandemic has raised uncertainty over the safety of the use of immunosuppressant drugs such as TP among healthcare care providers and patients, as there is a scarcity of data on whether IBD patients are at higher risk of COVID-19 infection or more prone to its severe outcomes. AIM: This review aims to encapsulate evidence on the risk of COVID-19 infection and its severe prognosis in IBD patients on TP. Additionally, it also evaluates the role of TP in inhibiting the viral protease, a potential drug target, essential for the replication and pathogenesis of the virus. CONCLUSION: Emerging evidence suggests that TP therapy is safe during the current pandemic and does not carry an elevated risk when used as monotherapy or in combination with other IBD drugs. In-vitro studies demonstrate that TP is a potential therapeutic for present and future betacoronavirus pandemics.

Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation.

Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.

A perplexing cause of upper GI Bleed.

Valleculae is one of a potential source of GI bleed. The lesions in the valleculae may potentially be missed during the routine endoscopies and due diligence is required especially among patients with GI bleed where no source of bleed could be identified.

Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel.

Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-l-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data.

Colonoscopy induced ischemic colitis: An endoscopic and histological assay.

Colonoscopy is a safe and effective diagnostic modality for various ileo-colonic diseases. Though the procedure itself is a rare cause of ischaemic colitis. Fewer than 30 cases of ischaemic colitis caused by colonoscopy procedure have been reported in the literature to date. The colon is susceptible to ischemia due to its minor blood flow compared to other organs in the abdomen. The etiology of colon ischemia after colonoscopy is multifactorial. Endoscopists must be aware of this condition and its risk factors for risk minimization, early diagnosis and proper treatment.

Profile of patients with hepatocellular carcinoma: An experience from a tertiary care center in India.

BACKGROUND: The prevalence of hepatocellular carcinoma (HCC) is increasing worldwide and it is now the third most common cause of cancer-related death. HCC is becoming a major health burden with steadily increasing incidence globally. METHODS: This is an observational study over a 3-year period in a tertiary care center in India. Three hundred and thirty-nine patients diagnosed to have HCC were included in this study. Patients' clinical, etiological, radiological and cytohistological data and therapy offered were recorded and analyzed. RESULTS: Cirrhosis of the liver was seen in 73.2% of the patients. 16.8% of patients were asymptomatic at the time of presentation. Ascites (57.2%) and jaundice (22.4%) were the most common signs of hepatic decompensation. The most common etiology of HCC was cryptogenic/non-alcoholic fatty liver disease (NAFLD) in 51% of the patients, while hepatitis B and C were seen in 17.4% and 5.8% of the patients, respectively. Advanced and end-stage disease with Barcelona Clinic Liver Cancer (BCLC) stages C and D were seen in 62.4% of patients. 56.6% had Albumin-bilirubin (ALBI) score of 2, while 62.8% had Okuda stage II disease. High alpha-fetoprotein (AFP) levels (>400 ng/mL) were seen in 48.9% of patients. Macrovascular invasion and metastases were seen in 45.9% and 22.2% of the patients, respectively. 17.6% of patients had evidence of tumor thrombus. 14.5% of biopsy specimens showed associated steatosis/steatohepatitis along with confirmation of HCC. Only 26.6% of the cirrhotic HCC patients were diagnosed during surveillance. CONCLUSIONS: HCC due to unknown cause/NAFLD appears to be overtaking hepatitis B as the commonest cause for HCC. Despite the advances in diagnostic methods and surveillance, most cases of HCC tend to be diagnosed at advanced stages.

Liquid chromatographic methods in the determination of inosine monophosphate dehydrogenase enzyme activity: a review.

Inosine monophosphate dehydrogenase (IMPDH) is a crucial enzyme involved in the de novo synthesis of purine nucleotides. IMPDH activity is used to evaluate the pharmacodynamics/pharmacokinetics of immunosuppressant drugs such as mycophenolic acid and thiopurines. These drugs are often used to prevent organ transplant rejection and as steroid-sparing agents in autoinflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis. Numerous analytical techniques have been employed to evaluate IMPDH activity in biological matrices. However, hyphenated LC techniques were most widely used in the literature. This review focuses on hyphenated LC methods used to measure IMPDH activity and provides detailed insight into the sample preparation techniques, chromatographic conditions, enzymatic assay conditions, detectors and normalization factors employed in those methods.

Evaluation of subclinical left ventricular systolic dysfunction using two-dimensional speckle-tracking echocardiography in patients with Child-Pugh A and B cirrhosis: A case-control study.

BACKGROUND: Although studies have proven that liver cirrhosis affects cardiac hemodynamics by means of circulatory overload, they present with definite cardiac functional alteration mostly with end-stage disease. There is limited data on relationship between progression of cirrhosis, cardiac mechanics and sub-clinical dysfunction. This study was done to assess ventricular myocardial mechanics using speckle tracking and deformation imaging among Child-Turcotte-Pugh (CTP) classification A and B cirrhosis. METHOD: Seventy patients with cirrhosis of Child-Pugh A/B class and sixty-two healthy subjects were prospectively evaluated by standard conventional echocardiography and deformation imaging with rotational echocardiography. Clinical stage of liver cirrhosis was assessed by model for end-stage liver disease (MELD) scores and CTP classification. RESULTS: Mean ages of patients with cirrhosis and controls were 55.64±14 years and 52.24±12 years, respectively. Though left ventricular (LV) dimensions (end diastolic dimension: 47.27±4.6 mm vs. 45.03±3.8 mm, p = 0.003; end systolic dimension: 30.33±4.9 mm vs. 28.40±2.91 mm, p = 0.006) and volumes (end diastolic volume: 82.08±22.53 mL vs. 68.18±15.75 mL, p = 0.001; end systolic volume: 28.60±8.42 mL vs. 22.18±7.48 mL, p = 0.001) were significantly higher in patients with cirrhosis, mean ejection fraction (EF) by Simpsons method was higher among controls (65.83±5.79% vs. 68.35±5.79%, p = 0.009). Left atrial volume was higher in cirrhosis group indicating presence of diastolic dysfunction (41.24±14.10 mL vs. 26.08±6.4 mL, p = 0.001). Global longitudinal strain as assessed by speckle tracking echocardiography did not show statistical significant difference between two groups (-22.35±4.08% vs. -21.80±2.54%, p = 0.348). Median value of torsion parameters in patients with cirrhosis did not differ compared to controls (torsion in degrees: 2.46 vs. 2.79, p = 0.268). CONCLUSION: Patients with Child-Pugh A and B stages of cirrhosis present with preserved longitudinal strain, normal torsion but with subtle diastolic dysfunction. Higher MELD score may correlate with increased longitudinal strain possibly due to hyperdynamic state.

Predictors for oesophageal candidiasis in patients with liver cirrhosis.

Background and aim: Oesophageal candidiasis (OC) is one of the most common infections among patients with liver cirrhosis. The present study evaluates the potential predictors for OC among liver cirrhosis patients. Methodology: This retrospective study was conducted in the tertiary care centre of coastal Karnataka from January 2016 to April 2022. Patients aged 18 and above with a confirmed diagnosis of liver cirrhosis were selected. Patients were equally divided into two groups, i.e., case and control, based on the presence and absence of OC. Results: A total of 1513 patients with cirrhosis underwent upper gastrointestinal endoscopy. Of these, 50 (3.3%) were diagnosed with OC and taken into case group. An equal number of patients were selected in control group and matched for gender, age and etiology. Most participants were male (94%), with a mean age of 48.46±11.82 years. A lower serum creatinine value was noted among patients with OC. Binary logistic regression identified serum creatinine as an independent predictor for OC (OR: 7.65, 95% CI: 2.012-29.08; p-value: 0.003). The receiver operating characteristic curve for serum creatinine showed the highest significance with a cut-off of <0.86 mg/dL (AUC: 0.722). Conclusion: Serum creatinine is the independent predictor for OC among liver cirrhosis patients. The possible mechanism is that cirrhosis is a catabolic state in which muscle protein breakdown exceeds synthesis, resulting in decreased muscle mass and low creatinine levels. However, more prospective studies are required to evaluate the role of sarcopenia with OC among liver cirrhosis patients.