Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018-March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments.

PURPOSE OF REVIEW: Hepatitis D virus (HDV) infection is the most severe form of chronic viral hepatitis, with no FDA-approved therapy. Progress in the development of effective HDV treatments is accelerating. This review highlights how mathematical modeling is improving understanding of HDV-HBsAg-host dynamics during antiviral therapy and generating insights into the efficacy and modes of action (MOA) of new antiviral agents. RECENT FINDINGS: Clinical trials with pegylated-interferon-λ, bulevertide, nucleic acid polymers, and/or lonafarnib against various steps of the HDV-life cycle have revealed new viral-kinetic patterns that were not observed under standard treatment with pegylated-interferon-α. Modeling indicated that the half-lives of circulating HDV and HBsAg are ~ 1.7 d and ~ 1.3 d, respectively, estimated the relative response of HDV and HBsAg during different antiviral therapies, and provided insights into the efficacy and MOA of drugs in development for treating HDV, which can inform response-guided therapy to individualize treatment duration. Mathematical modeling of HDV and HBsAg kinetics provides a window into the HDV virus lifecycle, HDV-HBsAg-host dynamics during antiviral therapy, and the MOA of new drugs for HDV.

Oxygen saturation during donor warm ischemia time and outcome of donation after circulatory death (DCD) liver transplantation with static cold storage: A review of 1114 cases.

The donor operation and the hemodynamics during declaration resulting in donor warm ischemia time have been linked to the outcomes in donation after circulatory death (DCD) liver transplantation (LT). Scrutiny of the donor hemodynamics at the time of withdrawal of life support concluded that a functional donor warm ischemia time may be associated with LT graft failure. Unfortunately, the definition for functional donor warm ischemia time has not reached a consensus-but has almost always incorporated time spent in a hypoxic state. Herein, we reviewed 1114 DCD LT cases performed at the 20 highest volume centers during 2014 and 2018. Donor hypoxia began within 3 minutes of withdrawal of life support for 60% of cases and within 10 minutes for 95% of cases. Graft survival was 88.3% at 1 year and 80.3% at 3 years. Scrutinizing the time spent under hypoxic conditions (oxygen saturation ≤ 80%) during the withdrawal of life support, we found an increasing risk of graft failure as hypoxic time increased from 0 to 16 minutes. After 16 minutes and up to 50 minutes, we did not find any increased risk of graft failure. In conclusion, after 16 minutes of time in hypoxia, the risk of graft failure in DCD LT did not increase. The current evidence suggests that an over-reliance on hypoxia time may lead to an unnecessary increase in DCD liver discard and may not be as useful for predicting graft loss after LT.

Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial.

BACKGROUND AND AIMS: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV. APPROACH AND RESULTS: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation. CONCLUSIONS: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.

A large A(H3N2) influenza outbreak with a high attack rate in a drug user community in Italy, April 2022.

Despite the COVID-19 pandemic, influenza remains an important issue. Especially in community settings, influenza outbreaks can be difficult to control and can result in high attack rates. In April 2022, a large A(H3N2) influenza outbreak spread in the largest Italian drug-rehabilitation community. One hundred eighty-four individuals presented influenza-like symptoms (attack rate of 26.2%); 56% previously received the influenza vaccine. Sequence analyses highlighted a genetic drift from the vaccine strain, which may have caused the observed lack of protection.

Breath Methane Does Not Correlate With Constipation Severity or Bloating in Patients With Constipation.

GOALS: We aimed to study (1) if the breath methane level on glucose breath testing (GBT) was associated with constipation severity and (2) compare methane levels between patients with constipation and diarrhea. BACKGROUND: The breath methane level has been associated with constipation and its severity. However, a few recent studies have questioned these associations. STUDY: Patients presenting consecutively to a tertiary care gastroenterology motility laboratory for GBT were included. GBT was performed using 75-g glucose load following a standard, institutional protocol. Constipation and irritable bowel syndrome (IBS) severity was measured using Patient Assessment of Constipation Symptoms (PAC-SYM) and IBS-symptom severity scale (IBS-SSS). RESULTS: In the cohort of 79 constipated patients, there was no significant correlation between baseline or maximum methane levels with total PAC-SYM score. IBS-SSS or bloating severity also did not correlate with baseline or maximum methane levels. The baseline or maximum methane levels of ≥3 and 5 ppm were equally distributed among those with constipation (n=79) and diarrhea (n=122). Only baseline methane levels of ≥10 and ≥20 ppm significantly correlated with constipation (P<0.001 for both). CONCLUSIONS: We found that constipation and bloating severity did not correlate with methane levels on GBT. In addition, only higher baseline methane levels (≥10 and ≥20 ppm) significantly correlated with constipation as baseline methane levels up to 5 ppm were equally common in patients with diarrhea and constipation. Baseline methane levels had better correlation with constipation compared with maximum levels of methane achieved.

Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome.

INTRODUCTION: Crofelemer, the active compound purified from latex of Croton lechleri, has been shown to improve HIV and traveler's diarrhea and improve pain in women with irritable bowel syndrome-diarrhea (IBS-D). This trial evaluated the effect of crofelemer on abdominal pain in women with IBS-D. METHODS: Women with IBS-D were randomized to crofelemer (125 mg) or placebo twice daily for 12 weeks. The primary efficacy endpoint was overall change in percentage of abdominal pain/discomfort-free days. Post hoc analysis for Food and Drug Administration (FDA) monthly responders was performed for stool consistency, abdominal pain, and combined stool consistency and abdominal pain. RESULTS: A total of 240 women were enrolled. There was no significant difference in overall percentage of pain/discomfort-free day between the groups. In post hoc analysis, FDA abdominal pain monthly responders were significantly more likely during months 1 through 2 (58.3% vs 45.0%, P = 0.030) as well as during the entire 3 months (54.2% vs 42.5%, P = 0.037) in the crofelemer group when compared with placebo. However, there was no significant difference in the percentage of FDA stool consistency monthly responders or combined stool consistency and pain monthly responders between the groups. Crofelemer had a safety profile similar to placebo. DISCUSSION: Crofelemer did not significantly improve abdominal pain over placebo by the primary endpoint. However, it did based on the FDA abdominal pain monthly responder endpoint. This suggests that crofelemer may have a role in the treatment of abdominal pain associated with IBS-D. Further studies are warranted to evaluate the potential of crofelemer as a visceral analgesic.