"Real world" efficacy of bulevirtide in HBV/HDV-related cirrhosis including people living with HIV: Results from the compassionate use programme at INMI Spallanzani in Rome, Italy.

OBJECTIVES: We describe the preliminary results of bulevirtide compassionate use in patients with hepatitis B and delta virus (HBV/HDV)-related cirrhosis and clinically significant portal hypertension, including those living with HIV. METHODS: We conducted a prospective observational study of consecutive patients. Clinical evaluation, liver function tests, bile acid levels, HDV-RNA, HBV-DNA, hepatitis B surface antigen, and liver and spleen stiffness were assessed at baseline and after treatment months 1, 2, 3, 4, 6, 9, and 12. HIV-RNA and CD4+/CD8+ count were assessed in people living with HIV. The first drug injection was administered under nurse supervision, and counselling was provided and adherence reviewed at each visit. RESULTS: In total, 13 patients (61.5% migrants) were enrolled. The median treatment duration was 11 months. At month 6, mean alanine aminotransferase (ALT) levels fell by 64.5% and mean liver and spleen stiffness decreased by 8.6 and 0.9 kPa, respectively. The mean baseline HDV-RNA was 3.34 log IU/mL and 5.10 log IU/mL in people without and with HIV (n = 5) (p = 0.28), respectively. A similar mean decline was observed in both groups: -2.06 log IU/mL and -1.93 log IU/mL, respectively (p = 0.87). A combined response (undetectable HDV RNA or ≥ -2 log IU/mL decline vs. baseline, with ALT normalization) was achieved in 66% of subjects without and in 60% of patients with HIV. Patients with HIV showed persistently undetectable HIV-RNA and a progressive increase in CD4+/CD8+ cells during treatment. No patient discontinued bulevirtide because of adverse effects. CONCLUSIONS: Preliminary results suggest that bulevirtide is feasible and well-tolerated in populations with difficult-to-treat conditions, such as those with HIV/HBV/HDV co-infection and migrants, when special attention is given to patient education. HDV-RNA decline during treatment was similar in people living with and without HIV.

Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. CASES PRESENTATION: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. CONCLUSIONS: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Acute hepatitis associated with clopidogrel: a case report and review of the literature.

Drug-induced hepatotoxicity is a common cause of acute hepatitis, and the recognition of the responsible drug may be difficult. We describe a case of clopidogrel-related acute hepatitis. The diagnosis is strongly suggested by an accurate medical history and liver biopsy. Reports about cases of hepatotoxicity due to clopidogrel are increasing in the last few years, after the increased use of this drug. In conclusion, we believe that physicians should carefully consider the risk of drug-induced hepatic injury when clopidogrel is prescribed.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Varicella zoster virus infection presenting as isolated diplopia: a case report.

BACKGROUND: Involvement of trochlear nerve during Varicella Zoster Virus (VZV) Infection has been rarely described, and always in association with skin rash. CASE PRESENTATION: We describe the case of a patient with VZV infection presenting as isolated diplopia due to fourth cranial nerve palsy. The diagnosis has been obtained through the application of a standardized molecular diagnostic panel, and diplopia resolved after specific antiviral and corticosteroid therapy. CONCLUSION: This case evidences that clinicians should be aware of atypical VZV infection, even in the absence of the typical skin rash.

Utility of Liver Biopsy in the Diagnosis and Management of Possible Drug-Induced Liver Injury in Patients Receiving Antituberculosis Therapy: A Retrospective Study.

BACKGROUND: Drug-induced liver injury (DILI) secondary to ATT treatment (TB-DILI) is reported in 2-28% of patients. We present here a series of clinical cases of suspected DILI arising during antituberculosis treatment, studied with the aid of liver biopsy. METHODS: this was a retrospective descriptive study including 10 tuberculosis patients who underwent liver biopsy for suspected TB-DILI at the "Lazzaro Spallanzani" Institute from 2017 to 2022. RESULTS: Ten patients who underwent LB were extracted from the database and included in the retrospective study cohort. According to the clinical classification, eight patients had hepatocellular liver injury, one patient had cholestatic injury, and another had mixed-type injury. Histopathological diagnosis revealed liver damage due to DILI in 5/10 (50%) cases. In one case, liver biopsy showed necrotizing granulomatous hepatitis. CONCLUSIONS: Severe and persistent elevation of hepatic transaminases, hepatic cholestasis despite discontinuation of therapy, and other suspected hepatic conditions are indications for liver biopsy, which remains a valuable tool in the evaluation of selected tuberculosis patients with suspected DILI for many reasons. However, the decision to perform a liver biopsy should be based on clinical judgment, considering the benefits and risks of the procedure.

High prevalence of asymptomatic SARS-CoV-2 infection in a cohort of liver transplant recipients in central Italy.

Asymptomatic subjects account for 25 to 45% of SARS-CoV-2 infections, and in particular, subjects on mild immunosuppressive therapy may have symptoms masked and could spread virus for an extended period of time. To determine the cumulative incidence of symptomatic and asymptomatic SARS-CoV-2 infections and associated risk factors, we conducted a prospective clinical and serological survey in a cohort of 278 liver transplant recipients (LTRs) from Central Italy. Three different serology tests were performed every 4 months in 259 LTRs between April 2020 and April 2021: one based on raw extract of whole SARS-CoV-2 virus and two on specific viral antigens (nucleoprotein and receptor binding domain) to detect specific IgG, IgM and IgA. Hundred fifteen LTRs who reported symptoms or close contact with a SARS-CoV-2-positive subject, or had a positive serological result underwent molecular testing by standard screening procedures (RT-PCR on naso-pharyngeal swab). Thirty-one past or active SARS-CoV-2 infections were identified: 14 had positive molecular test (64% symptomatic), and 17 had positive serology only (18% symptomatic). SARS-CoV-2 infection was not statistically related to gender, age, obesity, diabetes, renal impairment, type of anti-rejection therapy or time from transplant. Asymptomatic SARS-CoV-2 cases (61.3%) were more frequent in males and in those with glomerular filtrate rate >50 ml/min. Overall, the addition of repeated serology to standard diagnostic molecular protocols increased detection of SARS-CoV-2 infection from 5.1% to 10.9%. Anti-SARS-CoV-2 seroprevalence among our LTRs (11.2%) is comparable to the general population of Central Italy, considered a medium-impact area. Only one asymptomatic subject (6%) was found to carry SARS-CoV-2 in respiratory tract at the time of serological diagnosis.

Clinical Characteristics of Acute Hepatitis E and Their Correlation with HEV Genotype 3 Subtypes in Italy.

Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8-98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52-4835 U/L); aspartate aminotransferase (AST), 659 (range 64-6588 U/L); and total bilirubin, 3.49 (range 0.4-33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680-895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.

Endocarditis and meningitis associated to nape piercing in a young female: a case report.

Body piercing is a social phenomenon on the rise especially among young people. This procedure may be complicated by serious bacterial and viral infections. We report a case of Staphylococcus aureus infective endocarditis and meningitis arising from the site of a nape piercing, after its removal. A 21-year-old Italian female was admitted to hospital with neurological impairment and sepsis. A diagnosis of endocarditis associated with meningitis by S. aureus, complicated by septic emboli in the brain, retina, skin and kidney, was formulated on the basis of modified Duke's criteria. The likely port-of-entry was the site of a nape piercing, removed two months before. In view of the widespread practice of body piercing, provision of correct and timely information concerning the associated serious risks is now imperative. Such information should emphasise the option for antibiotic prophylaxis, and the importance of careful local hygiene, even after piercing removal.

Molecular characterization of hepatitis A outbreak in the province of Rome, Lazio region, Italy, January-July 2013.

Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012. Phylogenetic analysis indicated that most, although not all, infections were attributable to the same monophyletic genotype IA strain identified in the contemporary Northern Italy outbreak. This strain is also very similar to previous isolates from Venezuela.

IP-10 is an additional marker for tuberculosis (TB) detection in HIV-infected persons in a low-TB endemic country.

OBJECTIVE: In Indian HIV-infected patients, IP-10 response to QuantiFERON-TB Gold In tube (QFT-IT) antigens has been associated to tuberculosis (TB). However, specificity for active TB was lower than that reported by QFT-IT, making accuracy for TB detection questionable. To investigate this uncertainty, likely due to India being highly endemic for TB, and to better identify TB correlates, we evaluated the IP-10-based assay in HIV-infected subjects in Italy, a low-TB endemic country. METHODS: 195 individuals were prospectively enrolled; 118 were HIV-infected (21 with active TB, 97 without active TB, and distinguished as high/low-TB-risk). QFT-IT was performed and IP-10 was evaluated by ELISA. RESULTS: Among the HIV-infected individuals, sensitivity for active TB was 66.7% by IP-10-based test and 52.4% (p = 1) by QFT-IT. IP-10-based assay showed a lower dependence on mitogen-response and CD4 counts than QFT-IT. Among subjects without active TB, a higher proportion of IP-10 responders was shown in high-TB-risk subjects than low-TB-risk subjects (40.0% vs 12.9%), similar to QFT-IT (37.1% vs 4.8%). Low-TB risk subjects showed 87.1% specificity for active TB by IP-10-based test vs 95.2% by QFT-IT. CONCLUSIONS: In a low-TB endemic country, besides IFN-γ, IP-10 response to QFT-IT is associated with active TB and TB risk factors in HIV-infected patients with lower dependence on mitogen-response and CD4 counts.

Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy.

The fitness of human immunodeficiency virus (HIV) in vivo depends on the interaction of a multitude of viral and host factors. The aim of this study was to analyze the biological phenotype and the intrinsic capacity of the HIV isolates with drug-resistance mutations to replicate efficiently in the absence of drugs. An open label multicenter cross-sectional study was undertaken on 28 HIV-infected patients failing antiretroviral treatment. The subjects were studied for CD4+ cell count, HIV viral load, syncytium-inducing phenotype, genotypic drug-resistance assay, and replication capacity of HIV isolates assessed by co-culture assay. All HIV isolates showed a decreased replication capacity compared with wild-type strains. The lowest replication capacity was detected in HIV strains with more than five drug-resistance mutations. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. Isolates with R5 biological phenotype had a higher number of resistant mutations than X4 isolates (P = 0.004). Particularly, the R5 phenotype was detected in all 6 isolates with more than 14 drug-resistance mutations. Patients with R5 strains had plasma viral load similar to patients with X4 strains, but marginally higher CD4+ cell counts, and their HIV isolates had significantly lower replication capacity of HIV isolates (P = 0.008). No patient carrying HIV with a maintained replication capacity had a viral load less than 30,000 copies/ml. In patients failing HAART, the detection of HIV isolates with the R5 biological phenotype correlates with CD4+ cell count, an impaired replication capacity, and a high number of drug-resistance mutations.