A look inside the gut as a clue to nutritional status.

PURPOSE OF REVIEW: Malabsorption and malnutrition are common gastrointestinal manifestations clinicians face, requiring diagnostic workup for effective diagnosis and management of the underlying cause. This review discusses recent advances in diagnostic approaches to malabsorption and maldigestion of macronutrients - lipids, proteins, and carbohydrates. We highlight underrecognized causes, available testing modalities, and ongoing diagnostic unmet needs. RECENT FINDINGS: Innovations in the diagnostic landscape are enhancing our understanding of malabsorption syndromes. Stool collection and handling is uncomfortable and commonly avoided. The objective quantification of stool lipids, bile acids, and gut enzymes is therefore underused in the diagnosis and management of common disorders such as exocrine pancreatic insufficiency, bile acid diarrhea, protein-losing enteropathy, and more. We review the recent advancements in spot quantification of stool fat and bile acid content, endoscopic imaging techniques such as endocytoscopy, confocal laser endomicroscopy, and optical coherence tomography and the future place in clinical practice. SUMMARY: Malabsorption and maldigestion represent significant challenges in clinical nutrition and gastroenterology. Through the integration of advanced diagnostic techniques, clinicians will be better equipped to tailor therapy and monitor treatment response, ultimately improving patient health outcomes. This review underscores the critical role of innovative diagnostic tools in accurately detecting and effectively managing gastrointestinal disorders linked to nutritional status.

Large-Caliber Empiric Esophageal Dilation Results in Sustained Improvement for Selected Patients With Nonobstructive Dysphagia.

INTRODUCTION: Empiric esophageal dilation (EED) remains a controversial practice for managing nonobstructive dysphagia (NOD) secondary to concerns about safety and efficacy. We examine symptom response, presence of tissue disruption, and adverse events (AEs) after EED. METHODS: We examined large-caliber bougie EED for NOD at 2 tertiary referral centers: retrospectively evaluating for AEs. Esophageal manometry diagnoses were also reviewed. We then prospectively assessed EED's efficacy using the NIH Patient-Reported Outcomes Measurement Information System disrupted swallowing questionnaire to assess dysphagia at baseline, 1, 3, and 6 months after EED. Treatment success was defined by improvement in patient-reported outcome scores. RESULTS: AE rate for large-caliber dilation in the retrospective cohort of 180 patients undergoing EED for NOD was low (0.5% perforations, managed conservatively). Visible tissue disruption occurred in 18% of patients, with 47% occurring in the proximal esophagus. Obstructive motility disorders were found more frequently in patients with tissue disruption compared with those without (44% vs 14%, P = 0.05). The primary outcome, the mean disrupted swallowing T -score was 60.1 ± 9.1 at baseline, 56.1 ± 9.5 at 1 month ( P = 0.03), 57 ± 9.6 at 3 months ( P = 0.10), and 56 ± 10 at 6 months ( P = 0.02) (higher scores note more symptoms). EED resulted in a significant and durable improvement in dysphagia and specifically solid food dysphagia among patients with tissue disruption. DISCUSSION: EED is safe in solid food NOD and particularly effective when tissue disruption occurs. EED tissue disruption in NOD does not preclude esophageal dysmotility.

Age, Race, Ethnicity, and Sex of Participants in Clinical Trials Focused on Chronic Pain.

There is limited data on equitable inclusion in chronic pain trials. We aimed to 1) identify the frequency of reporting age, race, ethnicity, and sex in clinical trials targeting chronic pain, and 2) compare sociodemographic representation to the United States (US) population. We examined US-based intervention trials for chronic pain initiated between 2007 and 2021 and registered on ClinicalTrials.gov. We 1) assessed the frequency of reporting each demographic variable, 2) compared representation with US population estimates, and 3) explored change in reporting over time. Of 501 clinical trials, the frequency of reporting was as follows: 36.9% reported older adults, 54.3% reported race, 37.4% reported ethnicity, and 100% reported sex. Rates of race and ethnicity reporting increased, but older adult age reporting decreased over time (ps < .00001). Compared to 2020 US population estimates, there was an equitable representation of older adults, under-representation of individuals identifying as American Indian or Alaska Native (.8% vs .6%), Asian (5.6% vs 2.9%), Black or African American (12.6% vs 12.2%), with more than one race (2.9% vs 1.2%), and Hispanic/Latino (16.9% vs 14.1%). There was an over-representation of individuals identifying as Native Hawaiian or Pacific Islander (.2% vs .5%) or White (70.4% vs 72.9%), and of females (50.8% vs 68.4%). Some representation rates varied by chronic pain condition. Reporting of older adult age, race, and ethnicity was low in chronic pain trials in ClinicalTrials.gov, reinforcing the need for adhering to reporting guidelines. Representation varied across trials compared with US population data, particularly among those identifying as Hispanic/Latino and certain minority racial groups. PERSPECTIVE: Despite initiatives to increase the reporting of demographic information, doing so in clinical pain trials is far from ubiquitous. Moreover, efforts to improve diversity in these trials continue to be insufficient. Indeed, Black, Indigenous, and People of Color (BIPOC) remain under-represented in clinical pain trials.

Safety of Pneumatic Dilation in Older Adults with Achalasia: An International Multicenter Cross-Sectional Study.

BACKGROUND: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. METHODS: An international real world cross-sectional study of patients undergoing PD between 2006-2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. RESULTS: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. CONCLUSIONS: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions.

Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life.

INTRODUCTION: Fabry disease is a rare multisystemic lysosomal disease resulting in variable manifestations of the gastrointestinal (GI), neurologic, cardiac, and renal systems. Whether GI manifestations are a result of gut dysmotility is undetermined. We aimed to explore GI manifestations in depth and their effect on patients with Fabry disease and to characterize gut motility. METHODS: We recruited adult patients with Fabry disease reporting GI manifestations. All patients answered a battery of questionnaires covering symptom severity, GI-specific quality of life, and effects of work/productivity and underwent a wireless motility capsule test to measure pan-gut motility. RESULTS: In 48 patients with Fabry disease, abnormal bowel habits and abdominal pain were the most common symptoms. Bloating, nausea, vomiting, and reflux were also prevalent. Neurologic manifestations were found in 95.8% of patients, along with their GI manifestations. Dysmotility was found in less than 35% of wireless motility capsule tests. Colon transit time was associated with constipation severity and Bristol Stool Scale. Several GI symptoms were associated with reduced quality of life, anxiety, and work/productivity, but not Fabry severity score. DISCUSSION: This is the largest study of GI manifestations in patients with Fabry disease that characterizes gut motility. We found little association between GI manifestations and motility indices, suggesting that visceral hypersensitivity may be a major driver of symptoms. GI symptoms affect different aspects of patients' lives, yet are not always well-discussed or optimally managed in Fabry disease. Disease severity scores when used for therapeutic decision making do not often include GI symptoms or their impact.

Esophagogastroduodenal Findings in Patients with Intraductal Papillary Mucinous Neoplasms.

The association between intraductal papillary mucinous neoplasms (IPMNs) and extra-pancreatic malignancies is controversial. This cross-sectional study compared esophagogastroduodenal findings in 340 IPMN patients to those of age- and gender-matched controls without known IPMNs who underwent esophagogastroduodenoscopies (EGDs) for similar clinical reasons. The presence of gastric and esophageal cancer, Barrett's esophagus, neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), gastric adenomas, and ampullary tumors was assessed. The results showed that 4/340 (1.2%) of the IPMN patients had gastric cancer and 1/340 (0.3%) had esophageal cancer. The matched control group had a similar incidence of gastric cancer (5/340) (1.5%), with no esophageal cancer cases (p > 0.999). The overall incidence of other esophagogastroduodenal conditions did not significantly differ between the IPMN patients and the controls. However, the incidence of gastric cancer in the IPMN patients was higher than expected based on national cancer registry data (standardized incidence ratio of 31.39; p < 0.001; CI 8.38-78.76). In conclusion, IPMN patients have a significantly higher incidence of gastric cancer compared to the general population. However, the incidence of esophagogastroduodenal findings, including gastric and esophageal cancer, is similar between IPMN patients and those who undergo an EGD for similar clinical indications. Further research is needed to determine optimal surveillance strategies for IPMN patients regarding their risk of developing gastric cancer.

Psychological Factors Associated With Adherence to Oral Treatment in Ulcerative Colitis.

INTRODUCTION: Medication nonadherence in patients with ulcerative colitis (UC) can result in frequent relapses, severe disease, and higher risk of colorectal cancer. Behavioral models relying on motivation and perceived competence, like the self-determination theory (SDT), have been implicated in nonadherence; however, the SDT has not been evaluated in the adult UC population. We sought to examine the association between adherence to oral medications in patients with UC and psychological distress, relationship with health care providers, motivation, and competence. METHODS: We performed a cross-sectional study within the Inflammatory Bowel Disease (IBD) Partners online registry in which participants completed a baseline survey including demographic information, IBD history, symptoms, medication adherence, and psychosocial factors. Members of the registry with a diagnosis of UC received an online follow-up survey that included baseline questionnaires and assessment of competence, motivation, and patient-physician relationship. Logistic regression models were performed to determine the relationship between psychosocial factors, adherence modifiers, and medication adherence. RESULTS: Of the 410 UC patients included, 29% had low adherence to their medications, 36% had medium adherence, and 34% had high adherence. In the multivariable analysis, younger patients, those with a lower perceived competence, and those with worse relationship with their providers were more likely to have lower adherence to their medications. CONCLUSIONS: Poor adherence to oral medications in UC was associated with lower perceived competence and worse relationship with providers. Further interventions based on the SDT can potentially improve adherence and optimize patient care.

In a cross-sectional study within the Inflammatory Bowel Disease Partners online registry, poor adherence to oral medications in adult patients with ulcerative colitis was associated with lower perceived competence and worse relationship with providers.

Pancreatic cyst fluid glucose: a rapid on-site diagnostic test for mucinous cysts.

Background: Pancreatic cystic fluid (PCF) analysis is frequently used for cyst diagnosis with carcinoembryonic antigen (CEA) being the most accepted biomarker. Low glucose levels in PCF were previously suggested as a marker for mucinous cysts. A bed-side glucometer is a point-of care, immediate, simple, and cheap method which requires a small volume of PCF. Objectives: The aim of our study was to identify the optimal glucose cut-off level for identifying mucinous cysts, evaluate the diagnostic accuracy of glucose compared to CEA, and validate glucometry against reference laboratory biochemical analysis. Design: A single-center prospective cohort study. Methods: Consecutive patients aged 18 and older, who underwent pancreatic cyst evaluation, at the Tel Aviv Medical Center between 2016 and 2021 were analyzed. Cyst type was defined based on clinical, laboratory, and radiologic findings. Glucose was measured using laboratory biochemical analysis and two glucometers. Receiver operating characteristic analysis derived sensitivity, specificity, and accuracy were calculated and McNemar test was used to compare between methods. Results: One hundred and one PCF samples were evaluated. The areas under the receiver operating characteristics curve for identifying mucinous cysts using glucometer, glucose laboratory, and their combination were 0.88 (p < 0.001), 0.92 (p < 0.001), and 0.93 (p < 0.001), respectively. A glucose level of 87 mg/dL was identified as the optimal laboratory glucose threshold value to detect mucinous cyst with a sensitivity of 90.9%, specificity of 83.3%, and accuracy of 89.3, higher in comparison to cyst fluid CEA. Furthermore, PCF glucose levels had the strongest association with mucinous cysts. Conclusion: Our findings suggest that PCF glucose level is more accurate than CEA for the diagnosis of mucinous cysts. Glucometry glucose level assessment demonstrated an excellent correlation with laboratory glucose measurements and may become a useful diagnostic test.

Barriers and Facilitators of Hepatitis C Care in Persons Coinfected with Human Immunodeficiency Virus.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.

Increased prevalence of colorectal neoplasia in patients with intraductal papillary mucinous neoplasms.

Background: The association between intraductal papillary mucinous neoplasms (IPMNs) and colorectal cancer (CRC) and polyps is controversial. Objectives: To compare the prevalence of CRC and colorectal polyps among patients with IPMN and matched average risk individuals. Methods: A match cross-sectional historical study comparing colonoscopy findings of 310 patients with IPMN cysts who underwent at least one colonoscopy examination from 2004 through 2019, with 310 age- and gender-matched average risk participants who underwent a screening colonoscopy. CRC and polyps were assessed in both groups. The prevalence and odds ratio were calculated. Results: CRC was diagnosed in 16 of 310 patients with IPMN (5.2%), and at least one polyp was detected in 96 patients (31%). The prevalence of CRC was greater among patients with IPMN than in matched individuals [5.2% versus 1.3%, p = 0.012, prevalence odds ratio (POR) 4, confidence interval (CI) 1.29-16.44]. The overall prevalence of polyps was not higher among patients with IPMN than in matched individuals (31% versus 26.8%, p = 0.291, POR 1.22, CI 0.85-1.76). However, the prevalence of colorectal adenomas with high-grade dysplasia was higher in patients with IPMN than in matched individuals (4.2% versus 1%, p = 0.02, POR 4.33, CI, 1.19-23.7). The prevalence of large polyps (i.e. more than 20 mm in size) was also greater in patients with IPMN than in matched individuals (6.1% versus 1.9%, p = 0.011, POR 3.6, CI, 1.29-12.40). Conclusion: Patients with IPMN have a significantly higher prevalence of CRC and advanced polyps than the average risk population. In view of our findings, we suggest that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken.

Long-term Antibiotic Treatment in Pouchitis-Patterns of Use and Safety.

INTRODUCTION: Pouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment. METHODS: In a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed. RESULTS: The cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures-more commonly in the ultra-long-term antibiotic users. CONCLUSIONS: Patients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

Social and Economic Exchange Between Social Workers and their Employers in the Context of their Sectorial Affiliation and Seniority.

Partial privatization creates organizational hybrids that can generate conflict between professional and institutional logic among social workers. Research is scant but necessary to identify better organizational approaches. Using the social and economic exchange (SEE) model, we examined Israeli social workers' perception of their relationships with their workplaces. To examine organizational affiliation and seniority impact on SEE, we conducted a two-way ANOVA on data from 824 social workers: 55.1% from government sector (GSO) 30.8% from 'third sector' (TSO), and 14.1% from for-profit sector (FPO) organizations. Our findings showed the SEE model identified ways organizations and their social workers manage sector hybridity. Social exchange among TSO social workers was higher than GSOs, but similar to FPOs. Economic exchange was higher in FPOs, compared to GSOs. Seniority related only to economic exchange, possibly signaling change among newer social workers. TSOs must strengthen their social exchange to maintain their advantage among social workers.

Fecal Calprotectin Is Increased in Pouchitis and Progressively Increases With More Severe Endoscopic and Histologic Disease.

BACKGROUND & AIMS: Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA. METHODS: A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18). RESULTS: Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] µg/g vs 550 [IQR, 250-1051] µg/g; P < .0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of >460 µg/g had >80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of <125 µg/g had over 80% specificity in predicting endoscopic remission. CONCLUSIONS: FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.

The Cardio-Hepatic Relation in STEMI.

BACKGROUND: Hepatic injury secondary to congestive heart failure is well described, however, only limited data exist about the possible impact of acute cardiac dysfunction on the liver. We aimed to explore the possible cardio-hepatic interaction in patients with myocardial infarction. MATERIAL AND METHODS: A single-center retrospective cohort study of 1339 ST elevation myocardial infarction (STEMI) patients who underwent primary coronary intervention between June 2012 to June 2019. Echocardiographic examinations were performed to assess left ventricular ejection fraction (LVEF) and central venous pressure (CVP). Patients were stratified into four groups by their LVEF and CVP levels: LVEF ≥ 45%, and CVP ≤ 10 mm/Hg (n = 853), LVEF < 45% with CVP ≤ 10 mm/Hg (n = 364), EF ≥ 45%, with CVP > 10 mm/Hg (n = 61), and LVEF < 45% with CVP > 10 mm/Hg (n = 61). Patients were evaluated for baseline and peak liver enzymes including alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin. RESULTS: Greater severity of cardiac dysfunction was associated with worse elevation of liver enzymes. We found a graded increase in mean levels of maximal ALT, first and maximal ALP, and first and maximal GGT values. Using propensity score matching to estimate the impact of cardiac dysfunction on liver injury, we chose patients with the worst cardiac function parameters: (LVEF < 45% and CVP >10 mm/Hg; n = 61) and compared them to matched patients with better cardiac function (n = 45). We found a significantly higher level of maximal ALT, first and maximal ALP, and GGT values in the group with the worst cardiac function parameters (p < 0.05). CONCLUSIONS: Among patients with STEMI, the combination of decreased LVEF and venous congestion was associated with liver enzymes elevation suggesting a possible cardio-hepatic syndrome.

[COMMUNITY ACQUIRED KLEBSIELLA PNEUMONIAE LIVER ABSCESS - REPORT FROM ISRAEL].

INTRODUCTION: Klebsiella pneumoniae is facultative anaerobic bacilli gram-negative bacteria. Klebsiella pneumoniae often causes urinary tract infections and sometimes causes community acquired pneumonia. During the past two decades, a distinct syndrome of Klebsiella pneumoniae with a pyogenic liver abscess was noted. The incidence is higher among patients with diabetes mellitus, and can cause serious complications, including bacteremia, meningitis, endophthalmitis and necrotizing fasciitis. The first cases were reported from Taiwan, but later, more cases emerged in other Asian countries. During recent years the incidence of Klebsiella pneumoniae liver abscess has increased globally, with cases also reported in Australia, New Zealand, West Europe and the United States. To the best of our knowledge, these are the first 2 cases described in Israel.

[COMMUNITY ACQUIRED KLEBSIELLA PNEUMONIAE LIVER ABSCESS - REPORT FROM ISRAEL].

BACKGROUND: Klebsiella pneumoniae is facultative anaerobic bacilli gram-negative bacteria. Klebsiella pneumoniae, often causes urinary tract infections and sometimes causes community acquired pneumonia. During the past two decades, a distinct syndrome of Klebsiella pneumoniae with a pyogenic liver abscess was noted. The incidence is higher among patients with diabetes mellitus, and can cause serious complications, including bacteremia, meningitis, endophthalmitis and necrotizing fasciitis. The first cases were reported from Taiwan, but later, more cases emerged in other Asian countries. During recent years the incidence of Klebsiella pneumoniae liver abscess has increased globally, with cases also reported in Australia, New Zealand, West Europe and the United States. To the best to our knowledge, these are the first 2 cases described in Israel.

Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy.

Chronic hepatitis C virus (HCV) infection is associated with cognitive impairment via several suggested mechanisms including direct neurotoxicity and minimal hepatic encephalopathy. The prevalence of HCV-related cognitive impairment and whether it is reversed by anti-viral therapy is unknown. We aimed to assess predictors and reversibility of cognitive impairment of HCV-infected patients after successful treatment. Consecutive HCV patients treated during the EMERALD study (AbbVie 3D regimen for protease inhibitors failure) underwent neuropsychological (number connection test A [NCTA] and digital symbol test [DST]) and neurophysiological (critical flicker frequency [CFF]) tests at baseline and at 12 weeks post-treatment. Patient self-reported outcomes (PROs) were prospectively collected. Patients with a history of hepatic encephalopathy were excluded. Thirty-two patients underwent the cognitive tests at baseline. Seven of them had abnormal CFF test findings. Twenty-five (25/32, 78%) patients had repeated evaluations 3 months post-treatment. High viral loads were significantly associated with abnormal CFF across fibrosis levels (area under the ROC curve 0.817). CFF results significantly improved following viral eradication, from 40.9 (interquartile range 38.6-42.9) at baseline to 41.5 (39.8-44), p = .042, at follow-up. Both NCTA and DST results improved, but not significantly. There was improvement in the PROs of general health perception and vitality. The NCTA and DST results were more significantly associated with PROs than CFF. This prospective interventional study showed greater cognitive impairment in HCV patients with high viral load and demonstrated partial reversibility of HCV neurotoxicity and subsequent improvement in PROs following treatment.