Immunotherapy has radically changed the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). PD-L1 expression is generally associated with efficacy of immunotherapy, with PD-L1 overexpressing (PD-L1 >50%) NSCLC patients deriving the greatest benefit. However, a consistent proportion of positive cases do not respond to treatment, while some PD-L1 negative patients gain a significant survival benefit. Mechanisms underlying these different outcomes remain largely unknown. The development of antibodies directed against immune checkpoint inhibitors (ICIs) could affect sensitivity and tolerability to treatment. Aim of the present study was to investigate whether patients receiving ICIs develop antidrug antibodies and if this event impact on drug efficacy and/or toxicity.

Molecular modifiers of KRAS G12C inhibitor (KRAS G12Ci) efficacy in advanced KRAS G12C-mutant NSCLC are poorly defined. In a large unbiased clinico-genomic analysis of 424 NSCLC patients, we identified and validated co-alterations in KEAP1, SMARCA4 and CDKN2A as major independent determinants of inferior clinical outcomes with KRAS G12Ci monotherapy. Collectively, co-mutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ~50% of those with early disease progression (PFS≤3 months) with KRAS G12Ci. Pathway-level integration of less prevalent co-alterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRAS G12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRAS G12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRAS G12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies.

Due to its devastating behavior and unfavorable prognosis, SCLC is the most recalcitrant lung neuroendocrine tumor to treat. Performance status (PS), stage, and liver metastases have historically been recognized as prognostic factors in SCLC. However, these variables are unable to adequately stratify patients. Recently, we found that the laterality of primary lesions independently affected the outcome of well-differentiated lung neuroendocrine tumors, with left typical/atypical carcinoids having the worse prognosis (La Salvia A, et al.

A case-control study involving 109 in-patients with chronic liver disease and 190 in-patients with no apparent liver disease was conducted to evaluate the seroprevalence of anti-HEV antibodies and the possible association with chronic liver disease. Among cases, the anti-HEV prevalence was 36(.)6% which increased significantly by age; among controls, the prevalence was 12(.)1% (P < 0(.)05) and was similar among age groups < 60 years. Among cases, aged > 50 years (OR 4(.)0, 95% CI 1(.)4-11) and the presence of end stage liver disease (ESLD) (OR 4(.)3, 95% CI 1(.)4-12(.)8) were associated independently with anti-HEV positivity. The mean optical density, determined by anti-HEV immunoenzymatic test, was significantly higher among patients with ESLD, compared to the other patients. These results indicate that there is a high seroprevalence of anti-HEV in patients with chronic liver disease and a possible association between HEV infection and/or anti-HEV production and advanced stage chronic liver disease.

Background and aims The association between alcohol consumption and the risk of liver disease remains unclear. The aim of our study was to determine liver morphological features directly related to the mean lifetime daily alcohol intake (LTDAI) in non-cirrhotic patients.Methods Medical records of all consecutive patients who reported alcohol consumption up to the time of hospital admission and who had undergone a liver biopsy in the Gastroenterology Unit of the University Hospital Centre of Tirana (Albania), were reviewed. Patients with established cirrhosis and/or with other possible causes of liver damage were excluded by the study.Results The histological features revealed in the biopsy samples of 51 non-cirrhotic patients were: steatosis in 46 patients (91 %), six of whom (13%) showed also alcoholic foamy degeneration; alteration of hepatocytes in 40 patients (78%), diffuse mononuclear inflammation in 37 patients (73%), polymorphonuclear inflammation in 11 patients (22%) and perivenular fibrosis in 18 patients (35%). Diffuse steatosis was directly correlated with alcohol consumption (P < 0.01). No association was found between alcohol consumption and the presence of degenerative alterations of hepatocytes, Mallory bodies or hepatocellular necrosis. Fibrosis was more prevalent in patients who reported a LTDAI >= 80 g in comparison with patients who reported a LTDAI >= 40 to < 80 g (48% vs 25%; P < 0.05).Conclusion In non-cirrhotic patients liver steatosis and fibrosis were more common features among patients who reported a higher alcoholic consumption, but no clear-cut association between typical histological features of alcoholic liver disease and alcohol consumption was found. (c) 2005 Lippincott Williams & Wilkins.

Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg‐positive and HBeAg‐negative chronic hepatitis B). A cross‐sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV‐DNA was measured with an in‐house PCR with a sensitivity of 10 4 copies/ml which uses primers encompassing the pre‐core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg‐negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti‐HBe‐positive and older patients. In more than 90% of the HBeAg‐negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre‐core mutation at nucleotide 1896 was found. Patients with HBeAg‐positive chronic hepatitis B were younger than HBeAg‐negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver‐disease patients, the age of peak prevalence was at least 10 years lower for HBeAg‐positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level. J. Med. Virol. 75:20–26, 2005. © 2005 Wiley‐Liss, Inc.

Sir, The decline in the incidence of Helicobacter pylori infection in developed countries1 should lead to a reduction in the burden of associated disease, notably peptic ulceration and gastric cancer. Patterns of H pylori incidence are difficult to demonstrate but can be deduced from prevalence studies. High prevalence of infection …

The present study examined the effect of hepatitis B virus (HBV) and alcohol intake, and the role of hepatitis delta virus (HDV) and hepatitis C virus (HCV) in the aetiology of chronic liver disease in Albania. A total of 106 cases of liver cirrhosis or chronic hepatitis were compared to 195 control patients without these or other liver diseases. Adjusted odds ratios were 52·7 (95% CI 22·7–122) for HBV surface antigen, 26·9 (95% CI 4·9–147) for anti-HCV, 26·2 (95% CI 3·1–221) for anti-HDV, 2.4 (95% CI 1·3–4·4) for lifetime alcohol intake and 2·3 (95% CI 1–5·5) for duration of alcohol intake. Although not significant, an interaction was suggested between HBsAg and anti-HCV and between HBsAg and alcohol intake. Our study underlines the role of hepatitis viruses in the development of chronic liver diseases. Additionally, it suggests that heavy alcohol intake may magnify the effect of HBV on these diseases. HBV vaccination and alcohol abstention appear to be important strategies to reduce the risk of liver cirrhosis and chronic hepatitis in Albania.