Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals.

BACKGROUND: Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited. OBJECTIVES: We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders. DESIGN: Retrospective cohort study. SETTING: Tertiary care centers. PATIENTS AND METHODS: This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up. MAIN OUTCOME MEASURES: Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up. SAMPLE SIZE AND CHARACTERISTICS: 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females. RESULTS: Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%). CONCLUSIONS: Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality. LIMITATIONS: Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen. CONFLICT OF INTEREST: None.

HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alfa-2a to ongoing tenofovir treatment: A randomized controlled study.

BACKGROUND/AIMS: The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance. PATIENTS AND METHODS: In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups. One group (add-on therapy) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir. Patients in the other group received only tenofovir 300 mg orally on a daily basis. Patients in both groups were followed up for a total of two years, and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance. RESULTS: Twenty-three patients were allocated to the PEG IFN and tenofovir (add-on therapy) group, and another 25 patients were recruited to the tenofovir monotherapy group. Before randomization, patients had received tenofovir for 1135 mean days (range203 to 1542 days). One patient (4.3%) in add-on therapy lost HBsAg and seroconverted. Within two years, mean HBsAg decreased significantly with add-on therapy (from 4753 IU/ml to 2402; P= 0.03); and it decreased from 5957 IU/ml to 4198; P= 0.09 in tenofovir monotherapy group. More patients in the add-on group developed serious side effects, with treatment discontinuation, and dose reductions (P = 0.3). CONCLUSION: PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3% of the patients. Add-on therapy patients had a significant decrease in HBsAg levels in two years; and no significant decrease in HBsAg levels with the tenofovir monotherapy. With no significant HBsAg clearance, the utility of this combination regimen is questionable.

Clinical, endoscopic, and radiologic features of three subtypes of achalasia, classified using high-resolution manometry.

BACKGROUND/AIMS: High-resolution manometry (HRM) has improved the accuracy of manometry in detecting achalasia and determining its subtypes. However, the correlation of achalasia subtypes with clinical, endoscopic, and radiologic findings has not been assessed. We aimed to evaluate and compare the clinical, endoscopic, and fluoroscopy findings associated with three subtypes of achalasia using HRM. PATIENTS AND METHODS: The retrospective clinical data, HRM, endoscopy, and radiologic findings were obtained from the medical records of untreated achalasia patients. RESULTS: From 2011 to 2013, 374 patients underwent HRM. Fifty-two patients (14%) were diagnosed with achalasia, but only 32 (8.5%) of these patients had not received treatment and were therefore included in this study. The endoscopy results were normal in 28% of the patients, and a barium swallow was inconclusive in 31% of the achalasia patients. Ten patients (31%) were classified as having type I achalasia, 17 (53%) were classified as type II, and 5 (16%) were classified as type III. Among the three subtypes, type I patients were on average the youngest and had the longest history of dysphagia, mildest chest pain, most significant weight loss, and most dilated esophagus with residual food. Chest pain was most common in type III patients, and frequently had normal fluoroscopic and endoscopic results. CONCLUSION: The clinical, radiologic, and endoscopic findings were not significantly different between patients with type I and type II untreated achalasia. Type III patients had the most severe symptoms and were the most difficult to diagnose based on varied clinical, radiologic, and endoscopic findings.

Pancreatic metastasis arising from a BRAF(V600E)-positive papillary thyroid cancer: the role of endoscopic ultrasound-guided biopsy and response to sorafenib therapy.

BACKGROUND: Lungs and bones are the most common sites for distant metastases from papillary thyroid cancer (PTC). Metastases to the pancreas are extremely rare. Here we present a man with pancreatic metastases from PTC, report our experience with sorafenib therapy, and discuss the role of endoscopic ultrasound (EUS)-guided biopsy in its diagnosis. PATIENT FINDINGS: A 56-year-old man underwent total thyroidectomy, right-modified neck dissection, and radioactive iodine (RAI) remnant ablation for PTC at age 47 years (in 2002). Between 2002 and 2007, he had three more neck surgeries, two RAI therapies, and external beam radiotherapy for persistent and subsequently metastatic PTC. In 2008, a computed tomography/positron emission tomography (CT/PET) scan showed an 18F-fluorodeoxyglucose (FDG)-avid pancreatic focus. Magnetic resonance imaging (MRI) revealed a pancreatic nodule at the same location. An EUS-guided biopsy confirmed the diagnosis of pancreatic metastasis from PTC, and molecular studies showed positive BRAF(V600E) mutation. He was treated with sorafenib for 6 months. Although a lung CT scan done 2 months after initiation of sorafenib suggested stability of the disease, MRI studies done at 3 and 6 months showed clear progression with an increase in the size of the lung and pancreatic metastases. Subsequently, he developed liver, bone, and omental metastases. He died in July 2011, 9 years and 8 months after the initial diagnosis of PTC and 20 months after discovery of the pancreatic metastasis. SUMMARY: A middle-aged man with PTC developed lung metastases despite multiple surgeries and RAI therapies. Seven years after the initial diagnosis, a pancreatic metastasis was accidentally discovered. Both the metastasis and the primary thyroid tumor are positive for BRAF(V600E) mutation. The lung and pancreatic metastases progressed while the patient was receiving sorafenib for 6 months, and the patient died 20 months after diagnosis of pancreatic metastasis. CONCLUSION: PTC rarely metastasizes to the pancreas. In this patient, an FDG PET scan and EUS-guided biopsy played important roles in the diagnosis. PTC metastases to the pancreas usually occur in otherwise advanced disease. In the patient presented here, sorafenib may have slowed disease progression but the overall utility of tyrosine kinase inhibitors in pancreatic metastases from PTC is not clear.