Metformin as adjuvant treatment in hepatitis C virus infections and associated complications.

Hepatitis C virus is an important global cause of hepatitis and subsequently cirrhosis and hepatocellular carcinoma. These infections may also cause extrahepatic manifestations, including insulin resistance and type 2 diabetes mellitus. These two complications can potentially reduce sustained virologic responses (SVR) in some drug regimens for this infection. Metformin has important biochemical effects that can limit viral replication in cellular cultures and can improve the response to antiviral drug therapy based on ribavirin and interferon. Clinical studies comparing treatment regimens with interferon, ribavirin, metformin with these regimens without metformin have demonstrated that metformin increases viral clearance, establishes higher rates of SVRs, and increases insulin sensitivity. Metformin also reduces the frequency of hepatocellular carcinoma in patients who have had SVRs. Larger treatment trials are needed to determine metformin's short-term and long-term treatment effects in patients with diabetes using newer antiviral drugs. In particular, if metformin reduces the frequency of cirrhosis and hepatocellular carcinoma, this would significantly reduce the morbidity and mortality associated with this infection.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Granulomatous Hepatitis Treated With Certolizumab Pegol.

Idiopathic granulomatous hepatitis is a rare condition characterized by hepatic granulomas with constitutional symptoms such as recurrent fevers, myalgias, and hepatosplenomegaly in the absence of infection or inflammatory disorder. Typical treatment and course of this disease consist of a course of steroids with rapid symptom resolution. However, symptoms may recur when steroids are tapered. In these circumstances, azathioprine, methotrexate, infliximab, and adalimumab have demonstrated good response. In this case, we present a patient who developed antidrug antibodies to infliximab and adalimumab and was the first documented case of this disease to be treated with certolizumab pegol. Our case highlights the novel efficacy of certolizumab pegol for idiopathic granulomatous hepatitis and its role in treating idiopathic granulomatous hepatitis with antidrug antibodies.

Esophageal Stent in Acute Refractory Variceal Bleeding: A Systematic Review and a Meta-Analysis.

Background: Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. Aim: To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Results: Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, I2 = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, I2 = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, I2 = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, I2 = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, I2 = 34). Conclusions: SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.

The Utility of Fecal Calprotectin in the Diagnosis and Management of Microscopic Colitis.

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn's disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis. Methods: The medical records of patients who have been diagnosed with collagenous colitis and lymphocytic colitis aged 18-89 years old were retrospectively reviewed. Patient characteristics were recorded in those who had fecal calprotectin measured. Results: There were 198 patients who were diagnosed with collagenous colitis and lymphocytic between October 1, 2015, and July 31, 2022. Twenty-three patients had fecal calprotectin levels measured and were included in this study. The mean age was 51.7 ± 7.8 years in all groups. Thirteen patients were female. Six patients (26.1%) were diagnosed with collagenous colitis, and 17 patients (73.9%) were diagnosed with lymphocytic colitis. The fecal calprotectin cut-off in this lab is 50 µg/g stool. Median fecal calprotectin levels were 30.1 µg/g (15.6, 122.5), 19.5 µg/g (16.5, 64.6), and 33.2 µg/g (15.6, 134.9) in all groups, collagenous colitis, and lymphocytic colitis, respectively. Conclusion: The utility of fecal calprotectin in diagnosing microscopic colitis is limited. Our study suggests the diagnosis should be based on histopathology tissue obtained during colonoscopy.

Lupus Pancreatitis Masquerading as Pancreatic Cancer: A Rare Clinical Presentation.

Systemic lupus erythematosus (SLE) is an autoimmune multisystemic inflammatory disease. SLE-associated pancreatitis is uncommon, and pancreatic cancer in SLE is very rare. Imaging findings in SLE with pancreatitis can mimic malignancy. Endoscopic ultrasound with fine-needle aspiration/biopsy can guide in the accurate diagnosis and management of SLE-associated pancreatitis.

Fecal calprotectin level in microscopic colitis: a systematic review and meta-analysis.

Background: There are no specific biomarkers for microscopic colitis (MC), and the diagnosis depends on histopathological tissue obtained during colonoscopy. Studies on the role of fecal calprotectin (FCP) in MC are limited. A literature search of PubMed, Embase, and Scopus was conducted from each database's inception through September 2022. Methods: A DerSimonian-Liard random-effects meta-analysis was performed to examine the standardized mean difference (SMD) in FCP levels between patients with MC and control patients with chronic diarrhea. Results: Six studies with 96 active MC patients and 200 controls were included in the meta-analysis. Random effects meta-analysis revealed that FCP was significantly and moderately elevated in patients with MC compared to the control group (SMD = 0.6 [95% CI 0.3, 1.0], P = 0.001). Imputing one effect size confirmed the observation that FCP is significantly higher in patients with MC than control subjects with chronic diarrhea (SMD = 0.5 [95% CI 0.2, 0.9], P = 0.004). Study heterogeneity between the SMDs was not significant (I2 = 41%, P = 0.1). Conclusion: These results indicate that FCP levels in patients with chronic diarrhea can help identify patients with MC. More studies with serial measurements of FCP would provide a better understanding of its utility in MC.

Diagnostic performance of contrast-enhanced ultrasound in diagnosing hepatic artery occlusion after liver transplantation: A systematic review and meta-analysis.

INTRODUCTION: Hepatic artery occlusion (HAO) is a significant complication post-liver transplantation. Doppler ultrasound (DUS) has been widely used as an initial screening test for detecting HAO; however, its performance is often not sufficient. Although other diagnostic tests such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), and angiogram are more accurate, they are invasive and have several limitations. Contrast-enhanced ultrasound (CEUS) is an emerging tool for detecting HAO; however, the results from previous studies were limited due to a small number of patients. Therefore, we aimed to evaluate its performance by performing a meta-analysis. METHOD: We performed a systemic review and meta-analysis of studies evaluating the performance of CEUS for the detection of HAO in an adult population. A literature search of EMBASE, Scopus, CINAHL, and Medline was conducted through March 2022. Pooled sensitivity, specificity, log diagnostic odd ratio (LDOR), and area under summary receiver operating curve (AUC) were calculated. Publication bias was assessed by Deeks' funnel plot. RESULT: Eight studies were included, with 434 CEUS performed. Using a combination of CTA, MRA, angiography, clinical follow-up, and surgery as the gold standard, the sensitivity, specificity, and LDOR of CEUS for detection of HAO were .969 (.938, .996), .991 (.981, 1.001), and 5.732 (4.539, 6.926), respectively. AUC was .959. The heterogeneity between studies appeared universally low, and no significant publication bias was found (p = .44). CONCLUSION: CEUS appeared to have an excellent performance for the detection of HAO and could be considered as an alternative when DUS is non-diagnostic or when CTA, MRA, and angiogram are not feasible.

Viral Triggered Celiac Disease: A Case Report.

Celiac disease (CD) is an autoimmune condition presenting with a wide variety of nonspecific gastrointestinal symptoms. It can be difficult to diagnose due to the vagueness of complaints such as diarrhea, anemia due to malabsorption, vitamin or electrolyte deficiencies, and/or failure to thrive. This condition is characterized by a sensitivity to ingested gluten-containing compounds. Blood tests can be used for screening, though confirmatory testing by a small intestine biopsy is needed for diagnosis. Viral infections can trigger autoimmune conditions in individuals. It is possible that viral infections, such as Ebsetein-Barr virus(EBV) or Cytomegalovirus (CMV), can trigger the clinical presentation of celiac disease in certain individuals with genetic predispositions. Early recognition of celiac disease is important to prevent both short and long-term complications and improve the quality of life for the individual. Here, we discuss a case where the patient developed celiac disease only months after a diagnosis of mononucleosis.

Microscopic Colitis: Pathogenesis and Diagnosis.

Microscopic colitis is a type of inflammatory bowel disease and is classified as either collagenous colitis or lymphocytic colitis. The typical presentation is chronic watery diarrhea. The disease occurs more frequently in women aged 60-65 years and is increasing in incidence. The pathophysiology of microscopic colitis remains poorly understood and has not been well-described with possible several pathogeneses. To date, the diagnosis of microscopic colitis depends on histological tissue obtained during colonoscopy. Other non-invasive biomarkers, such as inflammatory markers and fecal biomarkers, have been studied in microscopic colitis, but the results remains inconclusive. The approach to chronic diarrhea is important and being able to differentiate chronic diarrhea in patients with microscopic colitis from other diseases, such as inflammatory bowel disease, functional diarrhea, and malignancy, by using non-invasive biomarkers would facilitate patient management. The management of microscopic colitis should be based on each individual's underlying pathogenesis and involves budesonide, bile acid sequestrants, or immunosuppressive drugs in refractory cases. Cigarette smoking and certain medications, especially proton pump inhibitors, should be eliminated, when possible, after the diagnosis is made.

Hepatitis E Virus Infections: Epidemiology, Genetic Diversity, and Clinical Considerations.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are four main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans via undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection, and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Utility of repeat colonoscopy within 1 year: a patient-level analysis.

Patients undergo colonoscopies for colorectal cancer screening and for the evaluation of gastrointestinal symptoms. Analysis of large administrative databases has demonstrated that some patients undergo repeat colonoscopies at intervals inconsistent with current recommendations, but these studies do not provide patient-level details. The medical records of 110 patients undergoing repeat colonoscopies within 1 year of their index colonoscopies at a tertiary care hospital-based endoscopy center were retrospectively reviewed to determine patient demographics, gastrointestinal symptoms, and endoscopic findings. Thirty-five patients had poor bowel preparations, and 11 patients had a history of colorectal cancer. Thirty-four patients had polyps identified during their index colonoscopies, and 28 patients had no polyps identified during their index colonoscopies. Eleven patients in the nonpolyp group had new endoscopic findings identified during the repeat colonoscopies. Twenty patients who had polyps identified on their index colonoscopies had 44 polyps identified on repeat colonoscopies. Repeat colonoscopies within 1 year occurred relatively infrequently in this endoscopy center. Indications included poor bowel preparation with incomplete studies, colonic polyps with incomplete resection, multiple polyps resulting in the possibility of missed polyps, and new gastrointestinal symptoms.

Prolapsed anorectal malignant melanoma presenting as hemorrhoids.

Rectal bleeding in a patient with a history of hemorrhoids should not be ignored. It is often benign and resolves spontaneously without treatment. Here we present a case of anorectal malignant melanoma that presented with rectal bleeding and a prolapsed rectal mass.

Mycobacterium goodii central venous catheter-related bloodstream infection.

Mycobacterium goodii is a rapidly growing nontuberculous mycobacterium that was first described in 1999. Previous case reports of M. goodii have been associated with prosthetic tissue infection or soft tissue infection. To our knowledge, there is only one previous case report on M. goodii catheter-related infection. Here we report a case of central venous catheter infection with M. goodii complicated by bacteremia.