BACKGROUND: The influence of hybrid solvation models on the molecular structures and vibrational characteristics of g-aminobutyric acid (GABA) and a-aminoisobutyric acid (AIB) zwitterions was assessed by employing a variety of Density Functional Theory (DFT). The quantum chemical methods included the B3LYP and B3PW91 hybrid functionals and the 6‑311++G(d,p) basis set.
METHODS: The most stable conformation derived from the potential energy surface (PES) scans using the B3LYP/6-311++G(d,p) model chemistry for each studied molecule was predicted within a continuum environment represented by the COSMO and SMD solvation models. The stable structures were subsequently immersed in explicit/COSMO and explicit/SMD hybrid solvation models, where 10 and 8 water molecules were explicitly positioned around the functional groups of the GABA and AIB zwitterions, respectively. The number of water molecules chosen was sufficient to prevent proton transfer among the carboxylate group (COO-) and the ammonium group (NH3+) within each molecule under investigation. After optimizing the geometry of each hydrated complex, the normal vibrational modes were determined. The scaled theoretical frequencies obtained from the various model chemistries were then compared to available experimental data from infrared (IR) and Raman spectroscopy.
RESULTS: In the case of GABA and AIB molecules, the comparisons revealed that the B3LYP/6-311++G(d,p) model chemistry yielded wavenumber values that closely matched the experimental IR and Raman data, particularly when the explicit/SMD solvent was employed. The computed results indicate deviations of less than 4% when compared to the experimental data for the two molecules under investigation.

BACKGROUND: Glecaprevir/pibrentasvir is a novel anti-hepatitis C virus (HCV) drug, and it is currently the only drug available for patients with severe renal impairment. Here we report a case with renal dysfunction after an administration of glecaprevir/pibrentasvir.
METHODS: The case was 66-year-old Japanese man who turned out to be HCV-positive 14 years ago at the time of his second deceased renal transplantation. He had no prior history of HCV treatment. HCV genotype was serogroup 1, and baseline HCV-RNA was 5.3 LOG IU/mL. Since glecaprevir/pibrentasvir became available, he started to take it for treatment of HCV. His immunosuppressants were tacrolimus (trough levels 4.3∼6.5 ng/mL) and 5 mg of prednisolone. His baseline renal function was serum creatinine (Cr) 2.1 mg/dL and urine protein (-). Shortly after starting glecaprevir/pibrentasvir, the serum Cr started to increase. Serum Cr reached up to 2.92 mg/dL and urine protein was (+) at day 36. Right pleural effusion was observed while cardiac function was normal. His liver function had been consistently normal. We concluded glecaprevir/pibrentasvir was the cause of renal dysfunction as no other drugs were added. Immediately after discontinuation of glecaprevir/pibrentasvir at day 36, serum Cr decreased to 1.9 mg/dL and urine protein turned negative at day 64. Although the patient completed a half course of glecaprevir/pibrentasvir, HCV-RNA turned to be negative at day 36.
CONCLUSIONS: We experienced a case with renal dysfunction after the initiation of glecaprevir/pibrentasvir in deceased donor renal transplant recipient. Renal dysfunction caused by glecaprevir/pibrentasvir has not been reported so far.

现报道1例HCV基因3b型肝硬化代偿期经治2次患者，应用格卡瑞韦/哌仑他韦联合索磷布韦、利巴韦林治疗16周，其治疗疗效及出现的不良反应。患者治疗成功，且无明显不良反应，为中国相关数据积累具有一定的意义。.

Hepatitis C virus (HCV) exacerbation is relatively rare as compared with hepatitis B virus reactivation in patients treated with immunosuppressive or anticancer drugs. We herein present the first reported case of acute exacerbation of chronic hepatitis in a patient with HCV persistent infection caused by combination treatment with daratumumab (DARA), bortezomib, and dexamethasone (DVd therapy). A 79-year-old woman diagnosed as having chronic HCV infection 11 years prior without successful viral elimination was referred to our hospital for the treatment of acute liver injury. Multiple myeloma (MM; IgG-κ type) was diagnosed two years before referral and subjected to several treatments. She had commenced DVd therapy four months prior to admission. Since her liver enzymes did not normalize with drug discontinuation and hepatoprotective therapy, we suspected HCV exacerbation and began direct-acting antiviral (DAA) treatment with glecaprevir/pibrentasvir (GLE/PIB). Soon afterwards, her liver enzymes normalized, and she achieved a sustained virological response after 8 weeks of treatment. Clinicians should bear in mind HCV exacerbation when encountering chronic HCV with acute liver injury under MM treatment including a DARA-based regimen. In such cases, DAA therapy is an option when other urgent treatments are needed.

BACKGROUND: In patients with hepatitis C virus (HCV) and malignant lymphoma, hepatitis C flare during R-CHOP can result in discontinuation of treatment. However, appropriate therapeutic strategies for managing hepatitis C flare during R-CHOP have not been established, and this issue is complicated by conflicting results regarding the use of direct-acting antivirals in patients with uncontrolled malignancies.
METHODS: We report the first case of effective and safe treatment with on-demand 8-week glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in a patient with diffuse large B-cell lymphoma (DLBCL). The patient completed five additional courses of R-CHOP without hepatic toxicity. A complete response of DLBCL and a sustained virological response were observed at 24 weeks after glecaprevir and pibrentasvir completion.
CONCLUSIONS: On-demand, direct-acting antivirals could be a novel strategy for managing hepatitis C flare during R-CHOP.

Shortening therapy duration with direct-acting antiviral agents (DAAs) is desirable to pursue the WHO target of HCV eradication by 2030. We report two cases of HCV-infected women who achieved sustained virologic response after an ultra-short treatment with glecaprevir/pibrentasvir (G/P), discontinued due to cutaneous adverse events, and analyze similar cases reported in the literature. Female gender seems to be a prevailing characteristic in this group of patients. G/P, due to its pangenotypic and strong antiviral activity, may represent a candidate for a shortened DAA regimen in non-cirrhotic treatment-naive subjects.

Inmates have higher HCV prevalence than general population, representing a fundamental step towards HCV eradication. Our aim was to compare 8-week glecaprevir/pibrentasvir treatment in a case-control study between incarcerated and free patients. Eleven Italian prisons and six outpatient clinics were involved. Patients were matched for sex, risk factors, METAVIR grade, HIV and HBV co-infections. About 131 incarcerated (Group A) and 131 free patients (Group B) were included. Mean age was 43.0 ± 9.6 years and 42.8 ± 9.9 in Group A and B, respectively (P = .74). SVR rates were 96.2% and 99.2% in Group A and Group B respectively (P = .21). Five drop-outs occurred in Group A, one in Group B. Incarceration, being PWIDs and OST were not associated with SVR reductions (CI 95%). In conclusion, imprisonment does not influence unplanned interruptions or SVR rates when receiving short-term therapies. Short schedules with pangenotypic regimens could be a good approach to hard-to-reach populations, such as incarcerated patients.

BACKGROUND:  Relapses after therapy with direct-acting antiviral agents (DAA) in chronic hepatitis C virus (HCV) infections are rare due to high efficacy of interferon-free therapy regimens. The presence of resistance-associated substitutions (RAS) in proteins targeted by therapy can lead to lower rates of sustained virological response (SVR) in patients receiving DAA-therapy, and little evidence exists as to how to treat these patients.
METHODS:  We present a case of a multi-drug-resistant HCV-genotype-3a-infection in a 50-year-old female without confirmed cirrhosis but with advanced fibrosis (liver stiffness 11.6 kPa) and low viral load. Resistance testing revealed a Y93H mutation in the NS5A gene. Therapies using sofosbuvir and daclatasvir (1st), sofosbuvir, velpatasvir and ribavirin (2nd), and subsequently with sofosbuvir, velpatasvir, and voxilaprevir (3st) did not achieve SVR. Compliance was good with rapid negativity of HCV RNA at 4 weeks of treatment on all 3 occasions. No virological breakthrough was recorded with all regimens. As a rescue attempt, the patient received 24 weeks of sofosbuvir, glecaprevir/pibrentasvir, and weight-based ribavirin at 1000 mg. With this approach, she achieved SVR but developed hepatocellular carcinoma.
CONCLUSIONS:  The combination of sofosbuvir, glecaprevir/pibrentasvir and ribavirin could be a rescue therapy after previous relapses on DAA-therapy, especially in patients with relapse after therapy with sofosbuvir, velpatasvir, and voxilaprevir.
UNASSIGNED:  Rückfälle nach einer Therapie mit direkt antiviral wirkenden Substanzen (DAA) bei Patienten mit chronischer Virushepatitis C (HCV) sind aufgrund der hohen Wirksamkeit dieser Therapeutika selten. Das Auftreten von resistenzassoziierten Substitutionen (RAS) in Proteinen, auf die die Therapie abzielt, kann eine anhaltende Viruselimination (SVR) verhindern, und es existiert wenig Evidenz dazu, wie diese Patienten anschließend behandelt werden sollten.
UNASSIGNED:  Wir berichten von einer 50-jährigen Patientin mit einer therapieresistenten HCV-Genotyp-3a-Infektion ohne bestätigte Leberzirrhose, aber mit fortgeschrittener Fibrose (Lebersteifigkeit 11,6 kPa) und niedriger Viruslast. Resistenztestungen zeigten eine Y93H-Mutation im NS5A-Gen des Virus. Mehrere Therapieversuche mit Sofosbuvir und Daclatasvir (1.), Sofosbuvir, Velpatasvir und Ribavirin (2.) und mit Sofosbuvir, Velpatasvir und Voxilaprevir (3.) konnten kein SVR erreichen. Es ergaben sich keine Hinweise auf eine eingeschränkte Compliance, da es jeweils nach vier Wochen zu einer schnellen und über den Therapiezeitraum persistierenden Negativierung der Viruslast kam. Als letzte Alternative erhielt die Patientin eine 24-wöchige Therapie mit Sofosbuvir, Glecaprevir/Pibrentasvir und gewichtsadaptiert 1000 mg Ribavirin. Damit erreichte sie ein SVR, entwickelte aber ein hepatozelluläres Karzinom.
UNASSIGNED:  Die Kombination von Sofosbuvir, Glecaprevir/Pibrentasvir und Ribavirin kann eine effektive Therapie nach Rückfällen auf eine vorherige DAA-Therapie darstellen, insbesondere, wenn ein SVR nach Gabe von Sofosbuvir, Velpatasvir und Voxilaprevir ausbleibt.

Direct-acting antiviral agent (DAA)-based therapies have been the 1st choice of antiviral agents for chronic hepatitis C throughout the world. The treatment period of DAA-based therapy has been greatly shortened by the improvement of their efficiency. Thus, glecaprevir (GLE)/pibrentasvir (PIB) therapy has enabled the therapeutic period to be reduced from 12 to 8 weeks in cases of genotype 1 or 2 chronic hepatitis C without liver cirrhosis. Currently, there is no established rescue therapy for patients who experience treatment failure on GLE/PIB therapy; however, some patients have been rescued by other regimens, including sofosbuvir (SOF)/velpatasvir (VEL) plus ribavirin (RBV) therapy and GLE/PIB, SOF, and RBV therapy. We experienced the case of a DAA-naïve non-cirrhotic patient with genotype 2a who showed virologic relapse at post-treatment week 13 following 8-week GLE/PIB therapy. After we confirmed that he did not have resistance-associated substitutions against GLE or PIB, we tried to rescue the patient using prolonged (12-week) GLE/PIB therapy. Fortunately, a sustained virologic response was achieved without any adverse events. Although this was a single-case report and is assumed to be rare, the same regimen might be effective for treatment failure with 8-week GLE/PIB therapy.

Glecaprevir (GLE)/pibrentasvir (PIB) is a direct-acting antiviral regimen approved for patients infected with hepatitis C virus. No data are available on the safety and efficacy of this regimen when crushed and administered through a percutaneous endoscopic gastrostomy (PEG) tube. Here, we report a patient who successfully achieved a sustained viral response after treatment with GLE/PIB administered via a PEG tube. A 41-year-old female with chronic hepatitis C viral infection was referred to our department for treatment. She had a history of spina bifida and hydrocephalus, and she received a PEG tube for nutrition and medication due to an aftereffect of hydrocephalus. She received crushed GLE/PIB treatment through a PEG tube for 8 weeks and achieved a sustained viral response 12, without any treatment-related severe adverse events. This is the first documented case treated with GLE/PIB administered through a PEG tube. Based on this case report and a review of the literature, we discuss the safety and efficacy of direct-acting antiviral treatment via a PEG tube.