Real-World Evidence to Evaluate the Efficacy and Safety of Vonoprazan in Gastrointestinal Disorders in the Pakistani Population.

BACKGROUND AND AIM: While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population. METHODS: This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA. RESULTS: Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the second week of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients. CONCLUSIONS: The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

Correction: Real-World Evidence to Evaluate the Efficacy and Safety of Vonoprazan in Gastrointestinal Disorders in the Pakistani Population.

[This corrects the article DOI: 10.7759/cureus.48994.].

IL28B rs12980275 polymorphism shows association with response to treatment in Pakistani patients with chronic hepatitis C.

The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients.

Comparison of the histological and serological parameters of patients with hepatitis delta virus in active and inactive hepatitis B virus carriers.

OBJECTIVE: To assess the histological and serological parameters of patients with hepatitis delta virus (HDV) in active HBV versus inactive HBV carriers. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Medical Unit IV at Liaquat University Hospital, Jamshoro, Sindh, from June 2008 to September 2011. METHODOLOGY: This study included 49 consecutive inactive HBV carriers who were HBsAg-positive, HBV DNA-negative, anti-D antibody-positive, and HDV RNA-positive, as well as 277 patients with active HBV who were HBsAg-positive, anti- HDV antibody-positive, HDV RNA-positive, and demonstrated > 20,000 IU/mL HBV DNA and > 2 (ULN) serum glutamic pyruvic transaminase (SGPT). Informed consent was obtained from each patient. Liver biopsies were obtained and the staging of fibrosis was performed according to the METAVIR scoring system. Continuous variables such as age, SGPT, platelet count, and the HBV DNA level were computed as the mean ± standard deviation. Categorical variables such as gender and stage of fibrosis are expressed as percentages. All data were processed using SPSS version 16. RESULTS: This study included 49 patients in an inactive HBV group. Fibrosis stage 0 was observed in 37 (75.5%) patients and 12 (24.5%) were stage 1. Among the 277 patients with active disease, fibrosis stage 0 was present in 7 (2.5%) patients, stage 1 in 31 (11.2%) patients, stage 2 in 172 (62.1%) patients, stage 3 in 44 (15.9%) patients and stage 4 in 23 (8.3%) patients. CONCLUSION: HDV in active HBV carriers is severe on its initial presentation and requires prompt treatment whereas in inactive HBV carriers demonstrates an indolent course.

Efficacy of PEG-interferon based treatment in patients with hepatitis C refractory to previous conventional interferon-based treatment.

OBJECTIVE: To determine the efficacy of peg-interferon-based therapy in patients refractory to previous conventional interferon-based treatment and factors predicting sustained viral response (SVR). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Medical Unit IV, Liaquat University Hospital, Jamshoro, from July 2009 to June 2011. METHODOLOGY: This study included consecutive patients of hepatitis C who were previously treated with conventional interferon-based treatment for 6 months but were either non-responders, relapsed or had virologic breakthrough and stage ≥ 2 with fibrosis on liver biopsy. All eligible patients were provided peg-interferon at the dosage of 180 µg weekly with ribavirin thrice a day for 6 months. Sustained Viral Response (SVR) was defined as absence of HCV RNA at 24th week after treatment. All data was processed on SPSS version 16. RESULTS: Out of 450 patients enrolled in the study, 192 were excluded from the study on the basis of minimal fibrosis (stage 0 and 1). Two hundred and fifty eight patients fulfilled the inclusion criteria and 247 completed the course of peg-interferon treatment. One hundred and sixty one (62.4%) were males and 97 (37.6%) were females. The mean age was 39.9 ± 6.1 years, haemoglobin was 11.49 ± 2.45 g/dl, platelet count was 127.2 ± 50.6 103/mm3, ALT was 99 ± 65 IU/L. SVR was achieved in 84 (32.6%). The strong association was found between SVR and the pattern of response (p = 0. 001), degree of fibrosis and early viral response (p = 0.001). CONCLUSION: Peg-interferon based treatment is an effective and safe treatment option for patients refractory to conventional interferon-based treatment.

MELD era: is this time to replace the original Child-Pugh score in patients with decompensated cirrhosis of liver.

OBJECTIVE: To compare the predictive value of MELD (Model of end stage liver disease) and Child-Pugh (CP) scores in patients with decompensated cirrhosis of liver. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Medical Department, Liaquat University of Medical and Health Sciences, Jamshoro/ Hyderabad, from August 2006 to October 2007. METHODOLOGY: This study included 110 consecutive patients with decompensated cirrhosis of liver diagnosed either clinically or radiologically were followed-up during hospital stay. Studied variables included demographic data, cirrhosis related complications and investigations. Patients were classified according to original CP classification into A, B and C. MELD score was estimated from serum bilirubin, serum creatinine and INR (International normalized ratio) of the patients. Duration of hospitalization and in-hospital mortality were made as the end points of the study. T-test and Chi-square test were done for continuous and categorical data. Original CP and MELD score were compared by the ROC curve. 0.05 was kept as the level of significance. RESULTS: There were 110 patients with decompensated cirrhosis of liver. Mean age was 46.76+12.93 years. There were 72 (65%) male and 38 (35%) females patients. Hepatitis C was the most prevalent cause of cirrhosis of liver present in 60/110 (60%) cases. Ascites was present in 93/110 (83%) patients. The mean MELD scores were 2.23+0.712 (95% CI 2.09 - 2.36) and for CTP 2.52+0.586 (95%; CI 2.41-2.63). The outcome of the patients were 12 deaths (11%); 54 (49%) remained hospitalized for up to 14 days and 44 (40%) for > 14 days. The majority of deaths and prolong hospitalization were found in patients with MELD score > 15 as well as with Child-Pugh grade C. The c-statistic was 0.726 (p=0.001) for CP score, and 0.642 for MELD score (p=0.021). CONCLUSION: The MELD score was not found to be superior to CTP score for short-term prognostication of patients with cirrhosis in this study.

Frequency of hyponatraemia and its influence on liver cirrhosis-related complications.

OBJECTIVE: To evaluate the frequency, clinical associations and prognostic impact of hyponatraemia on cirrhosis related complications in patients with cirrhosis of liver. METHODS: In this case control study 217 cirrhotic patients consecutively admitted to our department from September 2006 to November 2007 were studied. Serum sodium levels were determined in all patients admitted. The cutoff level of 130 meq/l was chosen because it is widely accepted to define hyponatraemia in patients with cirrhosis while the level of 135 meq/L is the lower normal value. Patients were grouped on the basis of serum sodium concentration into (1) serum sodium <130 meq/L (Group 1) (2) serum sodium between 131 - 135 meq/l (Group 2), and (3) serum sodium >135 meq/l (Group 3). P values of less than 0.05 were considered as significant. The patients with hyponatraemia Group 1 (<130 meq/l) and group 2 (131-135 meq/l) were compared with group 3 (>135 meq/l) for the severity of liver disease, degree of ascites and other cirrhosis related complications such as hepatorenal syndrome, spontaneous bacterial peritonitis and hepatic encephalopathy. RESULTS: This case control study constituted 217 consecutive cirrhotic patients of which 141 (65%) were male and 76/217 (35%) were female. Hyponatraemia (sodium <130 meq/l) was found in 58/217 (26.7%) patients and 54/217 (24.9%) had serum sodium from 131-135 meq/l whereas 105/217 (48.4%) patients had serum sodium >135. Out of 58 patients with hyponatraemia, 48 were in Child-Pugh C class (p=0.001). Patients with serum sodium <130 meq/l had more severe ascites (p = 0.001) requiring frequent paracentesis and higher dosages of diuretics. Hepatic encephalopathy was more frequent in patients with serum sodium <130 meq/l (p= 0.001). The cirrhosis related complications were also significantly increased in patients with mild hyponatraemia (131-135 meq/l) than in patients with normal serum sodium (>135 meq/l). CONCLUSION: Hyponatraemia is frequent in cirrhotic patients. It is seldom spontaneous and has a negative influence on cirrhosis related complications.

Validation of three non-invasive markers in assessing the severity of liver fibrosis in chronic hepatitis C.

OBJECTIVE: To compare various biochemical markers i.e. APRI (AST to platelet ratio index), aspartate aminotransferase (AST) alanine aminotransferase (ALT) ratio, FIB-4 (AST, platelet, AST and age) with biopsy for assessing the severity of hepatic fibrosis in patients with hepatitis C. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Medical Department, Liaquat University of Medical and Health Sciences, Jamshoro, from July 2005 to March 2007. METHODOLOGY: Consecutive hepatitis C virus RNA positive and previously untreated patients were studied. Liver biopsy with histological evaluation and AST/ALT ratio, AST to platelet ratio index and FIB-4 were assessed in all patients. Receiver operative curves were developed. RESULTS: There were 158 patients (109 males, 49 females). On histological grounds non-advanced fibrosis (F0-1) was present in 74 (46.5%) of cases, whereas 84 (53.5%) patients had advanced (F2-4) fibrosis. The area under the receiver operating characteristic curves of APRI < 0.05-1 and FIB-4 < 1.45 were 0.7 and 0.74 respectively, which means that APRI < 1 and FIB-4 < 1.45 will exclude advanced fibrosis in 70% and 74% of patients respectively. An APRI of > 1 and FIB-4 will predict advanced fibrosis in 87% and 98% of patients respectively. AST/ALT ratio was inferior to both of these biomarkers. CONCLUSION: Both APRI and FIB-4 not only exclude minimal fibrosis but can predict advanced fibrosis in the majority of the patients. The simultaneous use of several indirect markers of liver fibrosis does not improve their diagnostic accuracy.