Beyond the Liver: Unveiling Rhabdomyolysis as a Rare Complication of Hepatitis A.

Hepatitis A is a mild self-limiting infection of the liver with spontaneous resolution of symptoms in most cases. However, clinicians should be aware of some commonly encountered complications and extrahepatic manifestations associated with hepatitis A for timely diagnosis and treatment. Rhabdomyolysis, an exceedingly rare complication of hepatitis A, is scarcely documented. We present a case of a 64-year-old man with symptoms consistent with rhabdomyolysis and an evanescent rash secondary to acute hepatitis A. He eventually recovered with conservative management. This case emphasizes the importance of recognizing and treating atypical presentations of acute hepatitis A infection. LEARNING POINTS: Recognition of atypical presentations: The case underscores the importance of recognizing and treating atypical presentations of acute hepatitis A infection. Clinicians should be vigilant for unusual manifestations of common infections, facilitating timely diagnosis and appropriate management.Understanding rare complications: Rhabdomyolysis is identified as an exceedingly rare complication of hepatitis A infection, which is scarcely documented in the literature. This case contributes to the growing understanding of extrahepatic manifestations associated with hepatitis A, emphasizing the importance of considering uncommon complications in the differential diagnosis, especially when typical clinical presentations are observed.Management strategies: The article discusses the treatment approach for rhabdomyolysis secondary to acute hepatitis A, which involves aggressive fluid resuscitation to prevent kidney damage from myoglobinuria, correction of electrolyte imbalances, and metabolic abnormalities. Additionally, vaccination against hepatitis A and advocating for sanitation measures are highlighted as important preventive strategies.

Evidence to Date: Clinical Utility of Tremelimumab in the Treatment of Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and is associated with significant health care costs and burden. Management of HCC is guided based on the Barcelona Clinic Liver Cancer (BCLC) system and includes liver transplantation, surgical resection, and liver-directed and systemic therapies. In recent years, there have been significant advancements in understanding the immunogenicity of HCC and this has led to approval of different targeted agents as well as immunotherapy for advanced HCC. Tremelimumab is a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody and has recently been approved in combination with durvalumab (a programmed death-ligand 1 [PDL1] inhibitor) as first-line therapy for advanced (Barcelona Clinic Liver Cancer Stage C) HCC. In this article, we review the different available systemic therapies for advanced HCC with special focus on the clinical utility of tremelimumab for the treatment of unresectable HCC.

Polyarteritis Nodosa Associated With Hepatitis C Virus Infection.

Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis that affects medium-sized arteries. The association of hepatitis B virus (HBV)and HIV with PAN is well documented. Although there are documented cases of PAN in patients with hepatitis C virus (HCV) infection, the connection between PAN and HCV is not well established. We report a case of PAN in a patient with HCV infection who failed treatment with interferon.

Combined Hepatocellular Neuroendocrine Carcinoma: A Rare Tumor.

Neuroendocrine tumors originate from neuroendocrine cells primarily located in the gastrointestinal tract. These tumors often metastasize to the liver. Primary hepatic neuroendocrine carcinomas are uncommon, and combined hepatocellular neuroendocrine carcinomas are exceedingly rare. There is a lack of data on the management of these rare tumors. Most cases have very poor prognosis secondary to aggressive behavior of the neuroendocrine tumor component. It is important for clinicians to be aware of this rare carcinoma to allow for early diagnosis and optimize potential treatment options.

Hepatocellular Carcinoma Recurrence as Isolated Adrenal Metastasis.

Hepatocellular carcinoma is the sixth most common cancer in the Western world. The most frequent sites of metastasis are lungs, lymph nodes, and bones. Risk factors for extrahepatic metastasis are advanced intrahepatic lesions, vascular invasion, elevated tumor markers, and viral hepatitis. Isolated metachronous adrenal metastasis occurring after liver transplantation is exceedingly rare.

Polypoid Gastric Adenomyoma: A Rare Cause of Bleeding Treated With Polypectomy.

Gastric adenomyoma is a rare tumor composed of smooth muscle fibers and glandular tissue. Usual presentations include nausea, bloating, and gastric outlet obstruction. We describe a case of a 60-year-old woman who presented with abdominal pain and melena. Endoscopy showed a 1.5 cm polyp in the stomach body that was resected using snare polypectomy. Biopsy showed glands mixed with fibromuscular tissue consistent with gastric adenomyoma. We conclude that gastric adenomyoma, although rare, may present as a bleeding polyp in the stomach body and may be treated with excisional polypectomy.

Safety of Percutaneous Endoscopic Gastrostomy Placement in Patients With SARS-CoV-2 Infection.

Background: Coronavirus disease 2019 (COVID-19) can lead to ventilator-dependent chronic respiratory failure and a need for tube feeding. Percutaneous endoscopic gastrostomy (PEG) placement provides more sustainable longer-term enteral access with fewer side effects compared to the long-term nasogastric tube placement. Bleeding is a recognized complication of PEG placement, and many COVID-19 patients are on antiplatelets/anticoagulants, yet minimal data exist on the safety of PEG tube placement in this context. Methods: A retrospective chart review identified patients who underwent PEG placement between January 2020 and January 2021 at a single institution. Success was defined as PEG placement and use to provide enteral nutrition with no complications requiring removal within 4 weeks. Results: Thirty-six patients with and 104 age- and sex-matched patients without COVID-19 infection were included. More COVID-19 patients were obese, on anticoagulants, had low serum albumin levels and had a tracheostomy in place. Of those patients, 8.3% with COVID-19 developed PEG-related complications compared to 16.3% without (P = 0.28). PEG success rates in patients with and without COVID-19 were similar at 97.2% and 92.3%, respectively (P = 0.44). Conclusion: PEG tube placement is comparatively safe in COVID-19 patients who need long-term enteral access.

Bariatric surgery, obesity and liver transplantation.

The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.

Posterior Reversible Encephalopathy Syndrome (PRES) and Takotsubo: A Heart and Brain Affair!

Takotsubo cardiomyopathy (TC) is characterized by reversible left ventricle systolic dysfunction usually associated with stressors (physiological, psychological) being triggering factors. The increase in sympathetic activity, along with a subsequent surge of catecholamines, has been hypothesized as a possible etiology of TC. Posterior reversible encephalopathy syndrome (PRES), a relatively rare and recently recognized reversible clinico-radiological syndrome, is thought to share the same pathophysiology as TC. We present a case of an 83-year-old female who presented with seizures and was found to have PRES. Within three days of hospitalization, she developed takotsubo. She endorsed being under significant emotional stress that was thought to be the common culprit for both of her syndromes, i.e., PRES and TC.

Hospitalizations for Acute on Chronic Liver Failure at Academic Compared to Non-academic Centers Have Higher Mortality.

BACKGROUND AND AIM: Acute on chronic liver failure (ACLF) in patients with cirrhosis has high short-term mortality. Data comparing ACLF admissions to academic centers (AC) and non-academic centers (NAC) are scanty. METHODS: National Inpatient Sample (2006-2014) was queried for admissions with cirrhosis and ACLF using the ICD-09 codes, and was stratified to AC or NAC. RESULTS: Of 1,928,764 admissions with cirrhosis (2006-2014), 112,174 (5. 9%) had ACLF. 6.7% of 1,018,568 cirrhosis admissions to AC had ACLF versus 5% of 910,196 admissions to NAC, P < 0.0001. Proportion of ACLF admissions to AC increased from 49% during 2006-2008 to 59% during 2012-2014. In a cohort of 73,630 ACLF admissions (36,615 each to AC and NAC) matched for patient demographics, cirrhosis etiology, number of comorbidities, elective versus emergent admission, ACLF grade, and type of organ failure. In-hospital mortality declined by 7% over the study period, but remained higher in AC (46% vs. 42%, P < 0.001), with 11% increased odds for in-hospital mortality compared to admission to NAC. Further admissions to AC versus NAC had higher median (IQR) length of stay at 13 (6-25) versus 11 (5-20) days, with higher median (IQR) hospital charges: 138,239 (66,772-275,603) versus 116,209 (55,767-232,699) USD, P < 0.001 for both. CONCLUSION: Patients with ACLF have high in-hospital mortality. Further, this is higher among admissions to AC. Although the in-hospital mortality is improving, strategies are needed on early identification of patients with futility of care for early discussion on goals of care, and optimal utilization of hospital resources among admissions with ACLF.

Association Between Serological Markers and Crohn's Disease Activity.

BACKGROUND: The aim was to study the association between six serological markers and Crohn's disease (CD) activity at an inflammatory bowel disease (IBD) referral center. METHODS: We designed a retrospective cohort study using adults (> 18 years) with CD followed for at least 1 year at University of Alabama at Birmingham. Baseline serological markers ASCA-IgA, ASCA-IgG, anti-OmpC IgA, anti-CBir1 IgG, anti-A4Fla2 IgG and anti-FlaX IgG were drawn at initial visit. Poisson regression was used to assess the longitudinal relationship between these markers drawn at baseline and rate of active clinical disease during follow-up. RESULTS: Each marker, from 135 patients, was categorized into high vs. low. A Poisson regression model adjusted for age, gender, race, duration of disease, obesity, proton pump inhibitor; steroid and thiopurine use, and disease location demonstrated that CD patients with high anti-CBir1 IgG at baseline were approximately twice more likely to have active clinical disease (incidence rate ratio (IRR) 2.06, 95% confidence interval (CI) 1.28 - 3.33, P = 0.0032). The unadjusted Poisson regression model for A4Fla2 IgG antibody level did suggest that a high A4Fla2 IgG at baseline was associated with a higher likelihood of active CD (IRR 1.64, 95% CI 1.07, 2.53, P = 0.0238) which however, upon adjustment based on effect size, was not significant. The other four antibodies did not appear to predict clinical course. CONCLUSIONS: High levels of anti-CBir1 IgG appear to be associated with a greater likelihood of active CD. Whether routine baseline testing for anti-CBir1 IgG to predict a more active clinical course is warranted needs more research.

Comparative Effectiveness of Ustekinumab Versus Adalimumab in Induction of Clinical Response and Remission in Crohn's Disease: Experience of a Real-World Cohort at a Tertiary Care Inflammatory Bowel Disease Referral Center.

BACKGROUND: There is paucity of head-to-head studies comparing the effectiveness of ustekinumab (UST) and adalimumab (ADA) in Crohn's disease (CD). Here we provide a real-world comparison of these two agents. METHODS: We conducted an ambidirectional cohort study. Each patient included had moderate to severe active CD. Clinical response and remission were assessed between 4 and 16 weeks after induction. RESULTS: Of a total of 163 patients, 97 were induced with ADA and 66 were induced with UST. Logistic regression model analysis adjusted based on effect size showed that ADA when compared to UST induced clinical response (73.2% vs. 50% (odds ratio (OR): 2.40; 95% confidence interval (CI): 1.14 - 5.07; P = 0.02)) and remission (44.3% vs. 27.7% (OR: 2.35; 95% CI: 1.07 - 5.16; P = 0.034) in a statistically significantly higher proportion of patients. Among tumor necrosis factor (TNF)-naive patients, when comparing ADA vs. UST, ADA was superior in inducing clinical response (69/89 (77.5%) vs. 4/10 (40%) (OR: 4.26; 95% CI: 1.08 - 16.84; P = 0.04)), but not remission (41/89 (46%) vs. 3/9 (33%) (OR: 1.64; 95% CI: 0.39 - 6.97; P = 0.503)). Among TNF-experienced patients, ADA was numerically inferior in inducing clinical response (2/8 (25%) vs. 29/56 (52%) (OR: 0.38; 95% CI: 0.07 - 1.94; P = 0.24)) and remission (2/8 (25%) vs. 15/56 (27%) (OR: 1.22; 95% CI: 0.22 - 6.81; P = 0.82)), but neither of these differences were statistically significant. CONCLUSIONS: In a real-world setting, the rate of clinical response and remission was higher among patients with CD who received ADA compared to UST. Of note, however, despite the small sample sizes of TNF-experienced patients who received ADA and TNF-naive patients who received UST, the higher effectiveness of ADA in inducing clinical response and indeed remission among patients with CD with active disease appears to primarily be driven by those who are TNF-naive. Among TNF-experienced patients, UST may be superior in inducing clinical response and equally effective in inducing clinical remission when compared to ADA. Based on this study, one may infer that among TNF-experienced patients with CD with active disease, one could consider switching to an agent such as UST instead of a second approved TNF blocker. However, larger studies comparing the two agents are required.

NASH Is the Most Rapidly Growing Etiology for Acute-on-Chronic Liver Failure-Related Hospitalization and Disease Burden in the United States: A Population-Based Study.

Acute-on-chronic liver failure (ACLF) is characterized by multiple organ failure (OF) with high short-term mortality. There is lack of population-based data on trends on etiology specific ACLF related burden. National Inpatient Sample (2006-2014) was queried using ICD-09 codes for admissions with cirrhosis and ACLF (≥2 extrahepatic OF). Of 1,928,764 admissions for cirrhosis between 2006 and 2014, 112,174 (5.9%) had ACLF (4.5%, 1.2%, and 0.2% with ACLF 1, 2, and 3, respectively). The brain was the most common OF in 11.9%, followed by respiratory failure in 7.7%, cardiac failure in 6.3%, and renal failure in 5.6%. ACLF increased by 24% between 2006 and 2014 with a 63% increase in 179,104 patients with nonalcoholic steatohepatitis (NASH) cirrhosis (3.5% to 5.7%); a 28% increase in patients with 429,306 alcoholic cirrhosis (5.6% to 7.2%); a 25% increase in patients with 1,091,053 with other etiologies (5.2% to 6.5%); and no significant change in 229,301 patients with viral hepatitis (VH) (4.0% to 4.1%). In-hospital mortality was higher among ACLF patients compared with patients without ACLF (44% versus 4.7%; P < 0.0001). Each NASH-related ACLF patient compared with other etiologies had a longer mean length of stay (14 versus 12 days), was associated with higher median total charges (US $151,196 versus US $134,597), and had more frequent use of dialysis (45% versus 36%) and longterm care (32% versus 26%; P < 0.0001 for all). Results remained similar in a subgroup analysis after including half of admissions with cryptogenic cirrhosis as NASH. In conclusion, NASH cirrhosis is the most rapidly growing indication for ACLF-related hospitalization and use of hospital resources. In the setting of improved treatment options for chronic hepatitis, the health care burden of chronic viral-related liver disease remains stable. Population-based strategies are needed to reduce the health care burden of cirrhosis, particularly related to NASH.

Decreasing frequency and improved outcomes of hepatitis C-related liver transplantation in the era of direct-acting antivirals - a retrospective cohort study.

Benefit of direct-acting antivirals (DAA) for hepatitis C virus (HCV) on clinical outcomes is unclear. We examined temporal trends in liver transplant (LT) listings, receipt of LT, re-LT, and survival between pre-DAA (2009-2012) and DAA era (2013-2016) using UNOS database. Of 32 319 first adult LT, 15 049 (47%) were performed for HCV. Trends on listing, first LT, and of re-LT for HCV showed 23%, 20%, and 21% decrease in DAA compared to pre-DAA era (P < 0.0001). One-year liver graft and patient survival among HCV LT improved in DAA era (90% vs. 86% and 92% vs. 88%, respectively, P < 0.0001). Non-HCV LT showed no improvement in survival (89% vs. 89% and 92% vs. 92.4%, P = NS). On cox regression, compared to non-HCV LTs in DAA era, LT for HCV in pre-DAA era had worse patient survival (HR 1.56 [1.04-2.35]). The outcome was similar when compared to LTs for HCV in DAA era and for non-HCV in pre-DAA era. Burden of HCV-related LT waitlist and LT is declining in DAA era, with improved post-transplant outcomes, more so in later than earlier DAA era. Our findings negate recent Cochrane meta-analysis on DAA therapy and encourage studies to examine HCV clinical outcomes outside LT setting.

Autoimmune Enteropathy: An Updated Review with Special Focus on Stem Cell Transplant Therapy.

Autoimmune enteropathy (AIE) is a complex disease affecting both children and adults. Although associated with significant morbidity and mortality, the pathophysiology of the disease and its treatment have not been well characterized. This study aims to review the medical literature available on this rare but clinically significant ailment, to help establish a better understanding of its pathophysiology and enumerate the available diagnostic and treatment modalities. A literature search was conducted on PubMed using key terms related to autoimmune enteropathy and intractable diarrhea, with no restrictions on the date of publication or language. We found a total of 98 reports of AIE published in the form of case reports and case series. The evidence reviewed suggests that AIE is a multifaceted disorder that requires a high index of suspicion in the appropriate clinical setting to be able to make an early diagnosis. Current evidence supports the use of supportive care to correct nutritional and metabolic deficiencies, and immunosuppressives and immunomodulators as directed therapies. Hematopoietic stem cell transplant is an aggressive, but successful curative modality for patients with AIE as part of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Cumulative clinical experience with management of AIE has allowed improved outcomes in transplanted and non-transplanted AIE patients even though morbidity and mortality with are still high in patients with this condition. More research is needed to further define the role of new therapies for AIE, and a central registry with participation of multiple institutions might help share and standardize care of patients with this rare but serious condition.

Value-Based Health Care in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with significant resource utilization and health care burden. It is emerging as a global disease affecting an increasing proportion of the population. Along with evolving epidemiological trends, the paradigm of managing IBD has also changed. With a burgeoning repertoire of therapeutic options, improved use of health informatics, and emphasis on health care value, the treatment paradigm for IBD has experienced seismic shifts. In this review, we focused on value-based health care (VBHC)-a health care model that emphasizes monitoring outcomes to emphasize patient-centered, cost-effective IBD patient care. Several quality initiatives have been developed worldwide, and successful models of care were created for proper implementation of these initiatives. Although there are significant challenges to scale these models to a national level, it is still possible to successfully implement VBHC models within health systems to improve the quality of care provided to patients with IBD.

Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review.

Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.