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No consistently effective therapy is yet available for the treatment of chronic HBsAg, anti-HBe, HBV-DNA-positive hepatitis. A multicenter trial has shown that the response rates are not significantly different when patients with anti-HBe-positive hepatitis are treated with six-month course of thymosin-alpha1 or of interferon-alpha. However, since among these patients, interferon's real efficacy is still debated, with sustained biochemical response achieved in only a few of the treated patients, we conducted this controlled study to investigate the safety and efficacy of thymosin-alpha1 as compared with no treatment. Forty-four chronic hepatitis B virus (HBV) carriers, who were anti-HBe- and HBV-DNA-positive, were randomized, with stratification for the presence of cirrhosis at baseline liver biopsy, to receive either thymosin-alpha1 at a dose of 900 microg/m2 twice a week for six months or no treatment. At entry, both groups of patients were comparable for sex, age, liver histology, ALT, IgM anti-HBc, and HBV-DNA levels. Forty-two patients were followed-up for 20 months (median; range 12-32 months) after completion of therapy: one dropped out, and one developed hepatocellular carcinoma at six months. Thymosin-alpha1 treatment had no side effects. Six months after the end of the therapy, HBV-DNA was negative and ALT had normalized in 14% of treated cases and in 4.5% of control group, while IgM anti-HBc was negative (<0.200) in 14% of the treated patients and in 4.5% of the controls. Among the treated patients, the median ALT levels stayed significantly lower compared to the pretreatment values during the treatment period and six months of follow-up. During the first year, there were six flares of hepatitis in the control group and five among the treated patients (P = NS), yielding a per year average of 0.3 and 0.23 flares per patient, respectively. Among the treated patients, median IgM anti-HBc levels were low with respect to baseline values 4-10 months after treatment started. None became HBsAg negative. In conclusion, these results indicate that, in anti-HBe, HBV-DNA-positive chronic hepatitis B, thymosin-alpha1 therapy alone does not increase the response rate, but may contribute to reduce the immune-mediated liver cell necrosis as indirectly assessed by ALT and IgM anti-HBc levels. [ABSTRACT FROM AUTHOR]

Objectives: To report an outbreak of hypervirulent Klebsiella pneumoniae (hvKp) in COVID-19 patients., Methods: Prospective, observational study including consecutive COVID-19 patients with hvKp infections admitted to the University Hospital of Pisa (Italy). Clinical data and outcome of patients were collected. All patients were followed-up to 30 days from the diagnosis of infection. Mortality within 30 days of the diagnosis of hvKp infection was reported. The hypermucoviscous phenotype was determined by the 'string test'. Molecular typing was performed on three strains collected during different periods of the outbreak. The strains underwent whole genome sequencing using the Illumina MiSeq instrument. The complete circular assemblies were also obtained for the chromosome and a large plasmid using the Unicycler tool., Results: From November 2020 to March 2021, hvKp has been isolated from 36 COVID-19 patients: 29/36 (80.6%) had infections (15 bloodstream infections, 8 ventilator-associated pneumonias and 6 complicated urinary tract infections), while 7/36 (19.4%) had colonization (3 urine, 2 rectal and 2 skin). The isolates belonged to ST147 and their plasmid carried three replicons of the IncFIB (Mar), IncR and IncHI1B types and several resistance genes, including the rmpADC genes encoding enhancers of capsular synthesis. The hvKp isolates displayed an ESBL phenotype, with resistance to piperacillin/tazobactam and ceftolozane/tazobactam and susceptibility only to meropenem and ceftazidime/avibactam. The majority of patients were treated with meropenem alone or in combination with fosfomycin. Thirty-day mortality was 48.3% (14/29)., Conclusions: ST147 ESBL-producing hvKp is associated with high mortality in COVID-19 patients. Strict microbiological surveillance and infection control measures are needed in this population., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Interferon alpha (IFN-alpha) provides effective treatment in some patients with chronic hepatitis C. Since this drug is costly and causes potentially severe side effects, there is a need for clarification of the optimal dose regimen and treatment duration and of the predictive factors of long-term response to this therapy., Design: Prospective, randomized study in patients with chronic hepatitis C., Setting: 'Crespi' Division of Medicine and Centre for Liver Diseases, Niguarda Hospital, Milan, Italy., Patients and Methods: One hundred and forty-two patients with chronic hepatitis C were randomized to receive IFN-alpha at a dosage of 2-4 mega units/square metre of body surface area thrice weekly for 6-12 months. Eleven baseline variables that might predict sustained response to IFN-alpha were evaluated in this series. Sustained response was defined as normalization of transaminase levels observed by the fourth month of therapy and lasting for at least 6 months after treatment withdrawal., Results: According to univariate analysis, variables significantly associated with sustained response to treatment were: hepatitis C virus (HCV) genotype, treatment duration, serum HCV-RNA level and duration of hepatitis. On multivariate analysis only two of these variables were found to be independently associated with sustained response to IFN-alpha: HCV genotype (P < 0.0001) and treatment duration (P = 0.0015). In the patients infected with genotype 1b, IFN-alpha was effective only when administered at the higher dosage and for the longer period., Conclusion: Viral genotype and treatment duration are independently related to sustained response to IFN-alpha in patients with chronic hepatitis C. The patients infected with HCV genotype 1b should receive IFN-alpha at the higher dosage and for the longer period.

Introduction: Alpha interferon (alpha IFN) treatment normalizes serum ALT levels in at least half of all patients affected by chronic hepatitis C, but a reactivation of the disease is frequently observed after the end of therapy. Different regimens of alpha IFN therapy have been proposed but the optimal schedule is still controversial. Recently at least 6 different types of HCV have been identified and the HCV genotype has been proposed as an important factor influencing the response to alpha IFN therapy., Objective: The aim of this study was to evaluate the efficacy of different regimens of alpha IFN in chronic hepatitis C, and to study the relationship between the response to treatment and HCV genotypes., Methods: 160 consecutive patients affected by biopsy-proven chronic hepatitis C were randomly treated with different doses of lymphoblastoid alpha IFN [adjusted to the body surface area (m2)] and different durations of therapy, as follows: 2 MU/m2/t.i.w. for 6 or 12 months or 4 MU/m2/t.i.w. for 6 or 12 months. Biochemical and virological responses were studied: ALT levels were monitored monthly during and for at least 6 months after the end of treatment, and serum HCV RNA was assessed before and at the end of therapy, using nested RT-PCR. Biochemical responses were defined in advance as follows: non-response as maintenance of abnormal ALT levels during treatment; complete response as the normalization of ALT by the 4th month and lasting until the end of treatment; sustained response as a complete response lasting for at least 6 months after the end of therapy. The clearance of serum HCV RNA at the end of therapy was considered a virological response. In pre-treatment sera stored at-80 degrees, HCV genotyping was performed according to the method of Okamoto. The Chi square test and multiple stepwise logistic regression were used for the statistical analysis., Results: A sustained biochemical response was significantly more frequent in patients treated for 12 than in patients treated for 6 months, independently of the dosage (45% vs 24% in patients treated with 2 MU/m2/tiw, and 55.5% vs 30% in those treated with 4 MU/m2/tiw). The distribution of HCV genotypes (according to the classification of Okamoto) was 9.8% type I, 45.5% type II, 37.1% type III and 7.6% type V. Both the biochemical and virological responses were significantly correlated to the HCV genotype, being significantly more frequent in patients infected with type III or V (71-60% biochemical and 48-50% virological response, respectively) than in patients with type I or II (15% biochemical and 18-21% virological response, respectively)., Conclusions: 12 months of alpha IFN treatment seemed to be significantly more efficacious than 6 months of therapy, and a significant relationship between the HCV genotype and the biochemical and virological response to alpha IFN was found.

To investigate the usefulness of paracentesis as an alternative treatment for ascites, 41 cirrhotic patients with 'tense' ascites were randomly assigned to treatment with either repeated paracenteses plus i.v. albumin infusion (n = 20) or diuretics (n = 21). Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases. Ascites disappeared within 3 or 4 days with paracentesis, but only after 15 days with diuretics. The rate of reaccumulation of ascites following paracentesis, without diuretic administration, exceeded 300 g/day in only 5 patients. The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up. This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic, hepatic and renal function after evacuation of the ascites. These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating 'tense' ascites, and more rapid than traditional diuretic therapy.

Na+-K+-ATPase in canaliculi-enriched liver plasma membranes was found to be inhibited by high concentration of ethanol (12 mmoles %ml) both in vitro and in vivo; the decrease of Na+-K+-ATPase, which is considered a major factor in the production of bile-salt independent fraction of canalicular bile flow, may be the cause of the previously observed reduction of bile flow after ethanol administration.

Ethanol-fed rats showed significantly elevated plasma and liver gamma-glutamyltransferase activity, compared with rats fed carbohydrates isocalorically, or with untreated control animals. The activity of gamma-glutamyltransferase in liver was detected by means of both biochemical and histochemical methods. These data suggest that increased plasma gamma-glutamyltransferase activity commonly found in alcoholics can be related, at least in part, to a hepatic enhancement of the activity in the liver.