ACUTE VENOUS THROMBOEMBOLISM IS COMMON FOLLOWING ACUTE NECROTIZING PANCREATITIS AND IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES.

OBJECTIVES: While splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extra-splanchnic VTE (ESVT) is inadequately studied. Here, we aim to explore the incidence of VTE in acute necrotizing pancreatitis (ANP) and the associated mortality. METHODS: This is a retrospective cohort study utilizing an electronic health record database. Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate ICD-10-CM codes. The primary outcome was development of acute ESVT within one month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities. RESULTS: 17,942 (7.11%) patients were diagnosed with ANP during the study period and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTE, 61% were ESVT with or without SVT, and 63% (N = 1,799) were SVT. 90-day mortality (16.3% vs. 5.7%, risk ration, RR 2.86 [95% CI 2.29-3.56]) and 30-day rehospitalization (31% Vs 19%, RR 1.63 [95% CI 1.49-1.79]) were higher in patients with ESVT compared to non-VTE patients. 60% of patients with ESVT were on OAC and OAC use was associated with lower 90-day mortality (8.9% vs. 19.4%, RR 0.46) without increased risk of adverse events, like - acute gastrointestinal bleeding, intracranial bleeding, or need for packed red cell transfusion. CONCLUSIONS: Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay, and in the immediate ambulatory period.

Improving prognostication in patients with hepatocellular carcinoma undergoing loco-regional therapy using pre- and post-locoregional therapy scores.

BACKGROUND: Many scoring systems have been proposed for predicting survival in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT). We aimed to study the role of the NIACE score, hepatoma arterial embolization prognostic score (HAP), and ABCR score in predicting transplant-free survival (TFS) in these patients. METHODS: In this retrospective multicenter study of a United States Veteran cohort who underwent LRT, NIACE, HAP, and ABCR scores were calculated, and their predictive accuracy for TFS within different modified BCLC (mod-BCLC) stages was analyzed. RESULTS: 180 subjects underwent LRT between January-2012 and March-2019 were followed till January-2022, mean age 65.6 ± 6.3 years, model for end-stage liver disease -sodium (MELD-Na) score (at first LRT) 14.1 ± 6.7. A total of 43.9%, 35%, and 21.1% of patients had mod-BCLC A, B, and C stage disease, respectively. A total of 76.7% underwent transarterial embolization (TAE), 6.1% underwent ablation, and 17.2% underwent transarterial radioembolization (TARE) as the first intervention and were followed for a median of 576.5 patient-years. The NIACE score, HAP score, and ABCR scores differentiated patients within mod-BCLC stages A and B into groups with significant differences in TFS. In the stratified analysis of those undergoing only TAE, all three scores identified subgroups with significantly different TFS. CONCLUSION: In patients with HCC undergoing LRT, the mod-BCLC stages have subgroups with variable overall TFS. The NIACE score, HAP score, and ABCR score identified differential prognoses is within mod-BCLC stages and characterized subgroups with different TFS following LRT (TAE). Integration of these scoring systems into treatment decisions would help to improve prognostication within respective mod-BCLC groups, which may help with more customized treatment allocation.

A global multicenter propensity-matched analysis of mortality risk and palliative care referral due to cirrhosis in hospitalized patients with COVID-19.

Background and Aim: A few recent studies identified cirrhosis as a risk factor for high mortality in patients with coronavirus disease-19 (COVID-19). Palliative care is less often involved in the management of cirrhosis. We analyzed a global multicenter database to study the risk of mortality and palliative care referrals in patients with COVID-19 and cirrhosis. Methods: A federated cloud-based network (TriNetX) data from 50 health-care organizations across the globe were analyzed retrospectively. Patients with COVID-19 aged from 18 years to 90 years were identified between January 20, 2020, and November 16, 2020. Results: A total of 1969 patients (Group A) with COVID-19 and cirrhosis and 169,257 patients with COVID-19 alone (Group B) were studied. The two groups had a similar occurrence of other comorbid diseases. In a propensity-matched analysis, the mortality rate in Group A (8.9%) was significantly higher than Group B (5.6%), hazard ratio (95% confidence interval) for mortality with cirrhosis was 1.59 (1.26-1.99) (P = 0.01). The occurrence of palliative care referrals in Group A (4.1%) was significantly higher than Group B (2.0%), hazard ratio (95% confidence interval) with cirrhosis was 2.02 (1.39-2.94) (P = 0.01). Conclusion: Mortality rate and palliative care referrals were higher in patients with cirrhosis and COVID-19 compared to those with COVID-19 alone. This increased occurrence of palliative care referrals compared to the general trend in cirrhotic patients probably indicates increased awareness of COVID-19 as a life-threatening condition. Relevance for Patients: Cirrhosis should be identified as a high-risk condition that may require palliative care referral in hospitalized patients with COVID-19. Hospital resource utilization and cost-analysis modeling should anticipate the need for palliative care referrals as a significant outcome in patients with cirrhosis who are hospitalized with COVID-19.

COVID-19 and the liver: a narrative review of the present state of knowledge.

Novel corona virus disease (COVID-19) is an ongoing pandemic that has spread across the globe. The virus primarily infects type-2 pneumocytes in alveoli and causes lung disease, with severity ranging from mild pneumonia to acute respiratory distress syndrome. The virus also invades gastrointestinal epithelial cells, hepatocytes, and biliary epithelial cells. Derangement of liver function tests is noted in about one third of patients and appears to correlate with more severe disease. There are multiple mechanisms by which the virus can cause liver injury; immune-mediated inflammation and direct viral cytotoxicity are believed to be the predominant mechanisms. Liver injury appears to be transient, usually recovering with resolution of illness. Limited available studies and experience from prior corona virus pandemics seem to suggest that immunosuppressed patients have similar outcomes compared to non-immunosuppressed patients. Age and comorbid conditions seem to influence outcome, irrespective of immune status. Additionally, patients with preexisting comorbid conditions are more prone to acquire infection and should strictly adhere to travel and social distancing advisories. Telemedicine should be utilized to provide uninterrupted care for patients with liver disease, and clinic or hospital visits should be advised only in sick patients with advanced liver disease. In conclusion, liver dysfunction is not uncommon in COVID-19, it generally improves with resolution of disease, and patients with chronic liver disease (CLD) need continued follow up, uninterrupted by the ongoing pandemic, preferably in virtual clinic settings.

Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements.

Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.

Hereditary Hemorrhagic Telangiectasia and Refractory Ascites.

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disease that can involve the liver. The presence of arteriohepatic venous shunts can lead to high output cardiac failure and biliary ischemia, whereas arterioportal venous shunts can result in portal hypertension. Cirrhosis and nodular regenerative hyperplasia are also reported in these patients. Management of these patients in the setting of symptomatic liver disease is challenging. Transarterial embolization and hepatic artery ligation are usually considered palliative options. In selected cases, orthotopic liver transplantation can cure both liver disease and heart failure.

Acute Liver Failure due to Miliary Liver Metastasis.

Acute liver failure (ALF) is a medical emergency with high mortality. Accurate etiological diagnosis, intensive liver support, and liver transplantation are critical for the management of these patients. Malignant infiltration of the liver uncommonly results in ALF. Diffuse infiltration can be missed by imaging, particularly in early stages, and biopsy is often required to clinch the diagnosis. We report a case of ALF due to diffuse liver metastasis.

Targeting Hepatic Fibrosis in Autoimmune Hepatitis.

Hepatic fibrosis develops or progresses in 25 % of patients with autoimmune hepatitis despite corticosteroid therapy. Current management regimens lack reliable noninvasive methods to assess changes in hepatic fibrosis and interventions that disrupt fibrotic pathways. The goals of this review are to indicate promising noninvasive methods to monitor hepatic fibrosis in autoimmune hepatitis and identify anti-fibrotic interventions that warrant evaluation. Laboratory methods can differentiate cirrhosis from non-cirrhosis, but their accuracy in distinguishing changes in histological stage is uncertain. Radiological methods include transient elastography, acoustic radiation force impulse imaging, and magnetic resonance elastography. Methods based on ultrasonography are comparable in detecting advanced fibrosis and cirrhosis, but their performances may be compromised by hepatic inflammation and obesity. Magnetic resonance elastography has excellent performance parameters for all histological stages in diverse liver diseases, is uninfluenced by inflammatory activity or body habitus, has been superior to other radiological methods in nonalcoholic fatty liver disease, and may emerge as the preferred instrument to evaluate fibrosis in autoimmune hepatitis. Promising anti-fibrotic interventions are site- and organelle-specific agents, especially inhibitors of nicotinamide adenine dinucleotide phosphate oxidases, transforming growth factor beta, inducible nitric oxide synthase, lysyl oxidases, and C-C chemokine receptors types 2 and 5. Autoimmune hepatitis has a pro-fibrotic propensity, and noninvasive radiological methods, especially magnetic resonance elastography, and site- and organelle-specific interventions, especially selective antioxidants and inhibitors of collagen cross-linkage, may emerge to strengthen current management strategies.

Role of Nutrition and Muscle in Cirrhosis.

OPINION STATEMENT: Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, malnutrition and muscle wasting (sarcopenia) constitute common complications which negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Despite the important role that malnutrition and sarcopenia play in the prognosis of patients with cirrhosis, they are frequently overlooked, in part because nutritional assessment can be a difficult task in patients with cirrhosis due to fluid retention and/or overweight. Moreover, patients with cirrhosis may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of "sarcopenic obesity." In addition, muscle depletion is characterized by both a reduction in muscle size and increased proportion of intermuscular and intramuscular fat-denominated "myosteatosis." Sarcopenia in cirrhotic patients has been associated with increased mortality, sepsis complications, hyperammonemia, overt hepatic encephalopathy, and increased length of stay after liver transplantation. Muscularity assessment with cross-sectional imaging studies has become an attractive index of nutritional status evaluation in cirrhosis, as sarcopenia reflects a chronic detriment in general physical condition, rather than acute severity of the liver disease. In this review, we discuss the current diagnostic methods to evaluate malnutrition and muscle abnormalities in cirrhosis and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and muscle abnormalities in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduce morbidity related to cirrhosis. Finally, we analyze new studies including sarcopenia with the MELD score that seems to allow better prediction of mortality among cirrhotic patients waiting for liver transplantation.

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

BACKGROUND AND AIM: Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. MATERIALS AND METHODS: From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. RESULTS: The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10(9)/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. CONCLUSIONS: King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Renal dysfunction in cirrhosis: pathophysiology, diagnosis, and management.

The development of decompensation in patients with cirrhosis is associated with increased mortality. Renal function gradually deteriorates with significant hemodynamic changes associated with decompensated liver disease, but may also rapidly decrease in response to precipitating events. Newer definitions of renal dysfunction may result in early diagnosis, this along with the use of sensitive markers helps in accurate determination of renal function in cirrhosis. Although renal dysfunction progresses slowly in cirrhotic patients, it is associated with increased mortality. Prompt intervention with appropriate management reduces the risk of renal dysfunction, as well as improving survival and quality of life. Appropriate management may include the removal of precipitating causes and use of pharmacological agents supporting circulatory dysfunction. Outcomes following treatment of this condition remain a major concern, especially in patients who develop hepatorenal syndrome. Transplantation of the liver or kidney and liver may be the only option when other modalities of treatment fail. Early transplantation may benefit these patients.

Role of local ablative therapy for hepatocellular carcinoma.

Percutaneous local ablation (PLA) techniques are currently considered as the best treatment option for patients with early-stage hepatocellular carcinoma (HCC) who are not candidates for surgical resection. They are safe, minimally invasive, efficacious and cost-effective. Radiofrequency ablation (RFA) is considered as the first line treatment in some centers, though most of the guidelines recommend it for small HCCs, where surgical resection is not feasible. In developing countries percutaneous ethanol injection (PEI) and percutaneous acetic acid injection (PAI) may be used instead of RFA. For large HCCs, advances in electrode designs and newer techniques of ablation, including microwave ablation, are increasingly been used. Combination treatment modalities have shown promising results as compared to single modality for large tumors. The selection of the most appropriate modality depends on the size, number of lesions, the liver function status, patient's financial resources, availability of a particular technique and the expertise available.

The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

Melanoma of stomach.

INTRODUCTION: Melanoma of gastrointestinal tract can be either primary or secondary to metastases from other sites like skin, mucous membranes, and uvea. Primary gastrointestinal melanoma is rare and still rarer is stomach involvement. CASE REPORT: We report a case of primary malignant melanoma of stomach in a 50-year-old female who presented with an axillary lymphadenopathy. CONCLUSION: Melanoma of stomach is rare. It has characteristic endoscopic appearance. Differentiation of primary from secondary melanoma is possible on clinical behavior and histological characteristics.