Acalculous Cholecystitis in COVID-19 Patients: A Narrative Review.

Acute acalculous cholecystitis (AAC) represents cholecystitis without gallstones, occurring in approximately 5-10% of all cases of acute cholecystitis in adults. Several risk factors have been recognized, while infectious diseases can be a cause of cholecystitis in otherwise healthy people. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has spread worldwide, leading to an unprecedented pandemic. The virus enters cells through the binding of the spike protein to angiotensin-converting enzyme 2 (ACE2) receptors expressed in many human tissues, including the epithelial cells of the gastrointestinal (GI) tract, and this explains the symptoms emanating from the digestive system. Acute cholecystitis has been reported in patients with COVID-19. The purpose of this review is to provide a detailed analysis of the current literature on the pathogenesis, diagnosis, management, and outcomes of AAC in patients with COVID-19.

Acalculous Cholecystitis as a Complication of Primary Epstein-Barr Virus Infection: A Case-Based Scoping Review of the Literature.

Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively.

Acute acalculous cholecystitis due to hepatitis B virus reactivation: A case report and review of the literature.

We report a 52-year old man presenting with acute acalculous cholecystitis triggered by hepatitis B virus infection. The patient developed protective antibodies and cleared the infection. The relevant data is also discussed.

[Genome-wide Mendelian randomization study of the pathogenic role of gut microbiota in benign biliary tract diseases].

Objective: To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization. Methods: This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests. Results: Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.012) and cholecystitis (IVW OR=0.88,95%CI:0.80 to 0.97,P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95%CI:1.02 to 1.30,P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95%CI: 1.08 to 2.04,P=0.016) and cholecystitis (IVW OR=1.17, 95%CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95%CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95%CI:1.02 to 1.13,P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95%CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95%CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95%CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95%CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95%CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions: Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Current status and therapeutic strategy of acute acalculous cholecystitis: Japanese nationwide survey in the era of the Tokyo guidelines.

PURPOSE: This study aimed to clarify the incidence, therapeutic modality, and prognosis of acute acalculous cholecystitis and to reveal its optimal treatment strategy. METHODS: As a project study of the Japanese Society for Abdominal Emergency Medicine, we performed a questionnaire survey of demographic data and perioperative outcomes of acute acalculous cholecystitis treated between January 2018 and December 2020 from 42 institutions. RESULTS: In this study, 432 patients of acute acalculous cholecystitis, which accounts for 7.04% of acute cholecystitis, were collected. According to the Tokyo guidelines severity grade, 167 (38.6%), 202 (46.8%), and 63 (14.6%) cases were classified as Grade I, II, and III, respectively. A total of 11 (2.5%) patients died and myocardial infarction/congestive heart failure was the only independent risk factor for in-hospital death. Cholecystectomy, especially the laparoscopic approach, had more preferable outcomes compared to their counterparts. The Tokyo guidelines flow charts were useful for Grade I and II severity, but in the cases with Grade III, upfront cholecystectomy could be suitable in some patients. CONCLUSIONS: The proportions of severity grade and mortality of acute acalculous cholecystitis were found to be similar to those of acute cholecystitis, and laparoscopic cholecystectomy is recommended as an effective treatment option. (UMIN000047631).

Is conservative management a safe approach for patients with acute acalculous cholecystitis presenting with an acute abdomen?

Patients with acute acalculous cholecystitis (AAC) often present with acute abdominal symptoms. However, recent clinical studies have suggested that some patients with AAC and an acute abdomen, especially when caused by viruses or rheumatic disease, may not require cholecystectomy and that conservative treatment is adequate. Whether cholecystectomy is superior to conservative treatment for patients with AAC presenting with a severe acute abdomen is still uncertain. This was a case series study of AAC-related literature published between 1960 and 2022. In total, 171 cases (104 viral infection-associated AAC and 67 rheumatic disease-associated AAC) were included. The prognoses of patients receiving cholecystectomy or conservative treatment were compared. To account for confounding factors, etiological stratification and logistic regression were performed. The prognosis was similar for patients undergoing cholecystectomy and conservative treatment (P value .364), and virus infection-associated AAC had a better prognosis than rheumatic disease-associated AAC (P value .032). In patients with AAC caused by viruses or rheumatic disease, the acute abdomen can be adequately managed by conservative treatment of the underlying etiology and does not mandate surgical intervention.

Percutaneous cholecystostomy as a definitive treatment for acute acalculous cholecystitis: clinical outcomes and risk factors for recurrent cholecystitis.

OBJECTIVE: To investigate the outcomes of percutaneous cholecystostomy (PC) as a definitive treatment for acute acalculous cholecystitis (AAC) and to identify the risk factors for cholecystitis recurrence after catheter removal. METHODS: Between January 2008 and December 2017, 124 patients who had undergone PC as definitive treatment for moderate or severe AAC. The initial clinical success, complications, and recurrent cholecystitis after PC removal were retrospectively assessed. Twenty-one relevant variables were analyzed to identify risk factors for recurrent cholecystitis. RESULTS: Clinical effectiveness was achieved in 107 patients (86.3%) at 3 days and in all patients (100%) at 5 days after PC placement. Six Grade 2 adverse events occurred, including catheter dislodgement (n = 3) and clogging (n = 3), which required catheter exchange. The PC catheter was removed in 123 patients (99.2%), with a median indwelling duration of 18 days (range 5-116 days). During the follow-up period (median, 1624 days; range, 40-4945 days), five patients experienced recurrent cholecystitis (4.1%). The cumulative recurrence rates were 3.3%, 4.1%, and 4.1% at 6 months, 1 year, and 5 years, respectively. Multivariate analysis revealed that an age-adjusted Charlson comorbidity index (aCCI)≥7 positively correlated with recurrence (OR, 1.97; 95% confidence interval, 1.07-3.64; p = 0.029). CONCLUSIONS: Definitive PC is a safe and effective treatment option for patients with AAC. The PC catheters can be safely removed in most patients. An aCCI≥7 was a risk factor for cholecystitis recurrence after catheter removal. ADVANCES IN KNOWLEDGE: 1. Percutaneous cholecystostomy (PC) is a safe and effective as a definitive treatment in patients with acute acalculous cholecystitis (AAC).2. PC can be safely removed after recover from AAC in the majority of patients (99.2%) with low rate of recurrence of cholecystitis (4.1%).3. Age-adjusted Charlson comorbidity index ≥7 was a risk factor for recurrence of cholecystitis after PC removal.

Cholecystoenteric Stent-Related Complications: Rendering the Inoperable Patient Operable.

INTRODUCTION: Cholecystoenteric stenting is an alternative treatment for cholecystitis. However, complications with this approach can render a need for surgical intervention. METHODS: A case series of three patients undergoing surgery for a cholecystoenteric stent-related complication. RESULTS: Patient 1 was a 42-year-old male with history of lung transplant who had a cholecystoenteric stent placed for acalculous cholecystitis. One year later the stent became occluded with return of symptoms. Endoscopic replacement failed. A laparoscopic cholecystectomy with modified Graham patch was performed. Patient 2 is a 73-year-old female with acalculous cholecystitis in the setting of metastatic colon cancer on FOLFOX. Antibiotic treatment failed. A cholecystoenteric stent was attempted, but the stent dislodged during deployment. The fistula tract was clipped, and a percutaneous cholecystostomy drain was placed, which noted a leak at the gallbladder infundibulum. The patient deteriorated clinically and was taken emergently for an open cholecystectomy. Patient 3 was a 71-year-old male with history of ischemic cardiomyopathy who had a cholecystogastric stent placed for necrotizing gallstone pancreatitis. The stent migrated into the gastrointestinal tract and he developed post-prandial pain. A cholecystectomy and modified Graham patch repair of the gastrotomy was performed. This failed as the gastrotomy was too close to the pylorus. He underwent re-operation with Heineke-Mikulicz pyloroplasty. All patients recovered without any cardiopulmonary complications. CONCLUSION: With the increasing utility of cholecystoenteric stents, surgeons should be aware of the complications and have a plan for managing the duodenotomy or gastrotomy. Shared-medical decision-making involving surgeons should be applied when placing these stents.

Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition.

BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 ± 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 ± 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.

Cyclophilin D Regulates Oxidative Stress and Apoptosis via Mitochondrial Permeability Transition Pore in Acute Acalculous Cholecystitis.

OBJECTIVE: Acute acalculous cholecystitis (AAC) is characterized by acute onset, rapid progression, high mortality, and various complications. Cyclophilin D (CypD) regulates the mitochondrial permeability transition pore (MPTP) and is involved in the occurrence of ischemia-reperfusion injury and inflammation; however, the role of CypD in AAC remains unclear. METHODS: Guinea pigs of 300-350 g were randomly divided into three groups, namely the sham group, the common bile duct ligation-24h group (CBDL-24h group), and the CBDL-48h group. Western blot and qRT-PCR were applied to analyze the differential expression of CypD in each group, and transmission electron microscopy was employed to detect changes in mitochondrial structure. Inhibiting the activity of CypD by Cyclosporine A (CsA), we evaluated the difference of mitochondrial utilizing mitochondrial swelling, reactive oxygen species (ROS) detection and mitochondrial membrane potential. RESULTS: Compared with the sham group, the prolongation of obstruction aggravated gallbladder inflammation and upregulated CypD expression in the CBDL-24h and CBDL-48h groups. The degree of mitochondrial swelling was increased, and the opening of MPTP was prolonged in the CBDL-24h and 48h groups. Decreasing the expression of CypD could repress the opening of MPTP, prevent manipulation of the mitochondrial membrane potential, and ultimately diminish the levels of intracellular ROS and apoptosis. CONCLUSION: CypD plays a proinflammatory role in the development of AAC by regulating the opening of MPTP. Inhibiting the activity of CypD could reduce the levels of ROS and apoptosis, rescue the function of mitochondria and finally alleviate AAC. Therefore, CypD might serve as a potential therapeutic target for ACC.

PARAMETERS OF CENTRAL AND INTRACARDIAC HAEMODYNAMICS IN WOMEN WITH THYROID HYPERPLASIA AND ACALCULOUS CHOLECYSTITIS.

OBJECTIVE: Aim: The study aimed to investigate some parameters of functional status of central and intracardiac haemodynamics in women with thyroid hyperplasia and acalculous cholecystitis. PATIENTS AND METHODS: Materials and Methods: Functional changes of haemodynamic status in women with thyroid hyperplasia and acalculous cholecystitis were investigated. All data are obtained through general and special clinical methods, standard and special laboratory methods of examination, physiological, biochemical and statistical methods. Parameters of central and intracardiac haemodynamics have been recorded by the method of two-dimensional M-mode echocardiography in the echo chamber "Toshiba-140" (Japan) at the resting state. RESULTS: Results: An increase in heart rate (by 45.6%) was observed in patients, which led to decreased duration of cardiac cycle and ejection time. Statistically significant (p<0.05, 11.7% on average) increase in total peripheral vascular resistance was indicated. Dynamics of changes of parameters of central and intracardiac haemodynamics indicates different parallel existing pathways of secondary disturbances in the part of cardiovascular system. A significant increase in peripheral vascular resistance associated with decreased elasticity (increased vascular rigidity) of the arteries is the element of concentric type of left ventricular hypertrophy. The increase in volume in the absence of vasospastic reactions and increasing venous tone is an element of eccentric hypertrophy. CONCLUSION: Conclusions: It is possible to talk about the presence of systolic dysfunction in patients, which, however, is predominantly of functional character. The revealed specific changes in homeostatic haemodynamic characteristics in the women's body with thyroid hyperplasia and acalculous cholecystitis require the development of new, more effective and preferably drug-free (due to liver pathology and detoxification dysfunction) approaches to medical treatment of such patients.

Safe and effective short-time percutaneous cholecystostomy: A retrospective observational study.

The introduction of percutaneous cholecystostomy (PCT) has shifted the paradigm in treatment of acute calculous and acalculous cholecystitis. PCT has high success and low complication rates, but there are still unresolved issues regarding the duration of the procedure. The aim of our study is to determine the characteristics and outcome of patients treated with short-term PCT drainage. Patients who were admitted to the Department of gastroenterology and the Department of Abdominal Surgery at the University Hospital Center Split under the diagnosis of acute cholecystitis and who were treated with the PCT, in a period between January 2015 and January 2020, were retrospectively included in the study. During that timeframe we identified 92 patients and have analyzed their characteristics and clinical outcomes. The statistical analysis included the Kaplan-Meier method for calculating survival curves for grades 2 and 3, the log-rank test for testing the difference between survival rates of grade 2 and 3 patients, and logistic regression to determine variables that affected the outcome of our patients. According to the Tokyo guidelines, most of the patients (74, 80.43%) met the criteria for grade 2 cholecystitis, and the minority had grade 1 (9, 9.78%) and grade 3 (9, 9.78%) cholecystitis. The average drainage duration was 10.1 ±â€…4.8 (3-28) days. We identified mild complications in 6 cases. Nine patients (10%) had lethal outcome. The mortality in the largest group of patients with grade 2 cholecystitis was 5.48% and as high as 71.43% in patients with grade 3 cholecystitis. The complication rate was 6.5%. One quarter of gallbladder aspirates showed a ciprofloxacin resistance. Short-time PCT lasting approximately 10 days can be used safely and effectively for the treatment of patients with acute cholecystitis.

A rare case of acute acalculous cholecystitis secondary to hantavirus infection with renal syndrome.

Hantaviruses are single-stranded RNA viruses. They are transmitted to humans by rodents and insectivore hosts. Some Hantavirus subtypes are the causative agents of haemorrhagic fever with renal syndrome (HFRS), which is characterized by fever, thrombocytopenia, and acute kidney injury. Hantavirus infection is difficult to diagnose due to its non-specific clinical symptoms. Causes of acalculous cholecystitis are severe trauma or burn, surgery, long-term starvation and some viral infections. It is very rare for Hantavirus to cause acute acalculous cholecystitis. The treatment of acute acalculous cholecystitis is usually directed towards its symptoms. A 22-year-old male forest worker was admitted to our emergency outpatient clinic with the complaints of fatigue, oliguria, fever, abdominal pain and vomiting. After the clinical and laboratory examinations, HFRS and acute cholecystitis secondary to Hantavirus infection were diagnosed. The patient's condition and clinical findings improved after supportive treatment. Hantavirus infection should be considered in patients with acute kidney injury, cholecystitis and thrombocytopenia (Fig. 2, Ref. 10). Keywords: Hantavirus, acute kidney injury, acalculous cholecystitis, thrombocytopeni.

Acute acalculous cholecystitis following COVID-19 vaccination: a case report.

Acute acalculous cholecystitis is an acute inflammation of the gallbladder in the absence of stones, usually occurring in elderly and critically ill patients with underlying conditions. A 29-year-old man presented to the hospital complaining of abdominal pain in the right hypochondrium with permanent fever three days after Janssen COVID-19 vaccine inoculation. Abdominal ultrasound revealed a thickened gallbladder wall without evidence of gallstone consistent of an acute acalculous cholecystitis. Blood analyses revealed thrombocytopenia, eosinophilia and liver dysfunction. The Polymerase Chain Reaction (PCR) COVID-19 test was negative. As treatment, the patient benefited of pain management, antibiotic and fluid. In the evolution, there was a regression of clinical signs with persistence of liver dysfunction. The patient was discharged ten days after hospitalization. The Janssen COVID-19 vaccine is likely to induce acute acalculous cholecystitis as adverse event following vaccination.

A rare case of acute abdomen in a child with scrub typhus.

Acalculous cholecystitis and pancreatitis are rare complications of scrub typhus in children. In febrile patients from an endemic area with multisystem involvement, scrub typhus should be a differential diagnosis. Scrub typhus patients who develop abdominal pain, acute cholecystitis or pancreatitis should be suspected.