Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics.

BACKGROUND: Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients. AIM: To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP. METHODS: In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance. RESULTS: The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% (n = 175) of all patients, 100.0% (n = 74) of patients with portal vein thrombus, and 87.4% (n = 111) of patients with multicentric HCC. AFP was elevated in 64.3% (n = 130) of all the patients, 74% (n = 55) of the patients with portal vein thrombus, and 71.6% (n = 91) of the patients with multicentric HCC (P = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size (n = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients (P = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger (P < 0.001); however, the pairing among tumors < 2 cm size was not significant (P = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP. CONCLUSION: DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Point of Care Testing for SARS-COV-2 Antibodies before doing Endoscopy.

Objectives: COVID-19 has taken the world by storm, creating much disparity among both healthcare and non-healthcare centres regarding the provision of services. The purpose of our study was to see the prevalence of the SARS-COV-2 exposure in the asymptomatic patients undergoing the endoscopic procedure, already triaged based on history and examination. Methods: Total 207 patients were enrolled during a time period of five months during October 2020 to April 2021 at Dr. Ziauddin Hospital Clifton campus, Karachi. In this prospective observational study patients undergoing endoscopic procedures were included after taking informed consent. The patients who already tested positive for COVID-19 by PCR were excluded. Patients were tested for Covid serology by immunochromatographic rapid serology test (ICT). Standard Operating Procedures for dealing with endoscopy patients during the COVID era were followed in all patients irrespective of antibody status. Result: Total number of patients included was 207; males were 121 (58.5%). The mean age was 48.5 ± 17.55 (range 13 to 92). Forty eight patients (23.2%) were positive for either antibody suggesting exposure to the COVID-19 virus. Out of these combined IgM and IgG positivity was seen in 24 (11.5%), IgM mono antibody positivity was seen in 7 (3.38%) and 17 (8.21%) of the study population tested positive for IgG only. 15 out of 46 (32.6%) patients with chronic liver disease in the cohort were seropositive for COVID antibodies. Conclusion: About one-fourth of the patients undergoing the endoscopic procedure were tested positive for COVID antibodies of which a significant percentage had chronic liver disease. It stresses the need of observing standard precautions to prevent the spread of infection during these procedures, especially in the vulnerable population.

Incidence and predisposing factors for de novo post-COVID-19 irritable bowel syndrome.

OBJECTIVE: Postinfectious irritable bowel syndrome (IBS) is a known entity. We evaluated the incidence of post-COVID-19 IBS in patients discharged from the hospital and analyzed its correlation with the clinical and laboratory parameters, and treatment during the hospital stay. METHODS: Three hundred three COVID-19 hospitalized patients without prior history of IBS were prospectively followed after their discharge and were evaluated as per Rome-IV criteria for IBS. RESULTS: One hundred seventy-eight patients were males (58.7%). The age range was 17-95 years (mean ± SD, 55.9 ± 15.8). A total of 194 (64%) had mild COVID-19, 74 (24.4%) had moderate COVID-19, whereas 35 (11.6%) had severe COVID-19 infection. Sixteen (5.3%) patients had concomitant GI symptoms during COVID-19 infection. IBS symptoms were found to be present in 32 (10.6%) patients, out of which 17 (53.13%) had diarrhea-predominant, 10 (31.25%) had constipation-predominant, and five (15.62%) had mixed-type IBS. Post-COVID-19 IBS was more common in the female sex (P < 0.001), concomitant GI symptoms with COVID-19 (P < 0.001), oxygen requirement (P = 0.015), deranged liver function tests at the time of admission (P = 0.002), high procalcitonin (P = 0.013), high C-reactive protein levels (P = 0.035); whereas negative correlation was found with remdesivir treatment (P = 0.047). After performing regression analysis, female sex (P < 0.001), oxygen requirement during hospital stay (P = 0.016), GI symptoms during COVID-19 infection (P < 0.001), and high procalcitonin levels (P = 0.017) were independently associated with post-COVID-19 IBS. CONCLUSION: GI symptoms during active COVID-19 infection increase the chances of developing post-COVID-19 IBS. The risk of developing post-COVID-19 IBS increases in female patients, those requiring oxygen and having high procalcitonin levels during COVID-19 infection.

Patients visiting gastroenterology clinics avoid giving honest history for COVID-19 related symptoms in the pre-clinic triage.

OBJECTIVE: To assess the discrepancy in terms of history related to coronavirus disease-2019 and symptoms given in the pre-clinic triage and to the doctor attending the patient in a gastroenterology clinic. METHODS: The observational study was conducted from September 2020 to January 2021 at the Gastroenterology outpatient department of Dr Ziauddin Hospital's Clifton unit in Karachi, and comprised all patients visiting the facility regardless of age and gender. Data was collected using a questionnaire that was first filled up by the receptionist outside the clinic and was then administered again once the patient entered the clinic. Discrepancy on the answers was then checked and associations were determined with clinical assessment. Data was analysed using SPSS 20. RESULTS: Of the 300 patients, 184(61.3%) were males and 116(38.6%) were females. The overall mean age was 55 ± 16.98 (range: 18-92 years). Discrepancy between pre-clinic and in-clinic self-reported data was significant for fever, cough, fatigue, headache, body ache, diarrhoea, sore throat, loss of sense of smell/taste, shortness of breath, and contact with someone positive for coronavirus disease-2019 was significant (p<0.05). CONCLUSIONS: Patients were found to be afraid of getting barred from seeing a consultant, had fear of hospital-based isolation or were in denial regarding the pandemic.

Severe COVID-19 Associated With Liver Injury in Patients Without Preexisting Liver Disease.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is known to disturb liver function tests (LFTs). Not much literature is available regarding the effect of COVID-19 on LFTs in patients without preexisting liver disease. The study aimed to find the effect of COVID-19 in these patients. METHODS:  This was a single-center, observational study with 142 patients who were admitted with COVID-19 during three months. Seven patients were excluded due to the presence of chronic liver disease.  Results: A total of 135 patients were included in the study aged between 18 and 95 years (mean 57.7 ± 15.6); among them, 93 were males (68.9%). Hypertension was present in 74 patients (54.8%), and diabetes was present in 48 patients (35.6%). Fever was the chief complaint in 112 patients (83%), followed by dyspnea in 93 patients (68.9%) and cough in 79 patients (58.5%). Elevated aspartate aminotransferase (AST) was seen in 35 patients (26%), gamma-glutamyl transferase (GGT) in 43 patients (32%), alanine transaminase (ALT) in 18 patients (24%), alkaline phosphatase in 19 patients (14%), bilirubin in six patients (4%), and low albumin in 27 patients (20%). Severe COVID-19, when compared with mild to moderate disease, was associated with elevated AST > two-time upper limit normal (2ULN) (p = 0.002), GGT > 2ULN (0.026), and lower albumin (p = 0.020), higher systemic inflammatory response syndrome (SIRS) (0.045), raised procalcitonin (p = 0.045), higher ferritin (p = 0.005), lower pO2 (p = 0.044), and higher Sequential Organ Failure Assessment score (SOFA) (p = 0.002) pointing to the inflammatory response as cause of liver injury. Factors predicting mortality with COVID-19 were assessed, which showed that direct bilirubin (p = 0.001), low albumin (p = 0.013), tachypnea (0.002), and leukocytosis (<0.001) were independently associated with increased COVID-19-related mortality. CONCLUSION:  Patients suffering from COVID-19 have evidence of liver injury, which appears to be secondary to an inflammatory response that correlates with the severity of COVID-19.