Search

Aberrant squamous cell carcinoma antigen (SCCA) expression is an early event in hepatocarcinogenesis, and increasing serum levels of SCCA variants IgM immune complexes (SCCA-IgM IC) have been found in cirrhotic patients developing hepatocellular carcinoma (HCC). We longitudinally evaluated a cohort of cirrhotic patients with hepatitis C virus infection (HCV) who underwent pegylated interferon (PEG-IFN) and ribavirin treatment. SCCA-IgM IC levels were assessed in the sera of 33 cirrhotic patients with HCV (21 males, median age 57 years) before, at the end and at 6-month and 1-year follow-up after treatment with PEG-IFN and ribavirin. SCCA-IgM IC serum levels (arbitrary units/mL, AU/mL) were evaluated according to treatment outcome: sustained virological response (SVR) vs nonresponse (NR). Overall, 15 patients obtained a SVR to antiviral therapy (45%). There was no significant difference in baseline SCCA-IgM IC serum levels between SVR and NR patients. When compared to baseline (451.2 AU/mL), SVR patients showed a significant decrease in median SCCA-IgM IC serum levels at the end of treatment (186.8 AU/mL, P = 0.013) and at both 6-month (96.8 AU/mL, P < 0.001) and 1-year follow-up (52.4 AU/mL, P < 0.001), while no significant modification was observed in NR patients. In patients with HCV-related liver cirrhosis, successful antiviral therapy is associated with a dramatic and significant decrease in SCCA-IC serum levels. Because of the pathophysiological correlation between SCCA and liver carcinogenesis, it is hypothesized that in patients with liver cirrhosis, SVR may be accompanied by a decreased proliferative stimulation. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 502–508 Background There are few data in the literature regarding the long-term virological follow-up of chronic hepatitis C patients who obtain sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin therapy. Aim To assess the durability of SVR to PEG-IFN and ribavirin therapy during long-term follow-up of chronic hepatitis C patients. Methods We evaluated a cohort of 231 chronic hepatitis C patients who had at least 48 weeks of follow-up after SVR to PEG-IFN and ribavirin treatment. Median duration of follow-up after SVR was 164 weeks, and exceeded 5 years in 30% of the cohort. Patients underwent consistent clinical, biochemical and virological evaluations every 6 months during follow-up. Results Sustained virological response was maintained in 211 patients (91%) while HCV-RNA became positive in two patients (<1%) within 1 year after SVR, and in 18 patients (8%) serum HCV-RNA was transiently positive in at least one follow-up evaluation. Clinical outcome was not significantly different between patients with persistently negative and transiently positive serum HCV-RNA. Conclusions Sustained virological response to PEG-IFN and ribavirin is maintained in 99% of patients during long-term follow-up. Late virological relapse occurred within 1 year after SVR and, from a clinical perspective, patients can be considered cured of infection after this period. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 493–501 Background A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well-selected patients with unresectable hepatocellular carcinoma (HCC). Aim To access whether this information has modified the use of TACE in clinical practice. Methods From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4-year periods (1999–2002, n = 161 and 2003–2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival. Results Patients undergoing TACE increased in the 2003–2006 period (from 62% to 73%, P = 0.035), with an increase in of Child-Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999–2002 period, there was no significant difference in survival between TACE-treated and untreated patients, while in the 2003–2006 period, TACE-treated patients survived longer ( P < 0.0001). Conclusions Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well-compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage. [ABSTRACT FROM AUTHOR]

Objective. Therapy with full-dose pegylated interferon (PEG-IFN) and weight-based ribavirin has been evaluated in limited series of patients with hepatitis C virus (HCV) and advanced disease. In this study, we evaluated the efficacy and tolerability of full-dose antiviral therapy in patients with compensated, fully developed cirrhosis, and assessed the predictive value of on-treatment virological response. Design and subjects. We studied 85 HCV-positive cirrhotic patients (82 Child-Pugh class A; 41 treatment-naïve) who were treated with PEG-IFN α-2a (1.5 μg kg−1week−1) or α-2b (180 μg week−1) and weight-based ribavirin for 24 (genotype 2–3) or 48 (genotype 1–4) weeks. Forty-three patients were genotype 1 (51%), and HCV-RNA was >600 000 IU mL−1 in 53 patients (62%). Prevalence of portal hypertension and diabetes was 81% and 18% respectively. Results. Sustained virological response (SVR) was obtained in 22 patients (26%). Positive serum HCV-RNA at week 4 and week 12 of therapy predicted nonresponse (NR) in 85% (52/61) and 100% (38/38) of patients, respectively. Treatment was discontinued due to adverse events in 14 patients (16%). Genotype 1–4 ( P = 0.02) and HCV-RNA >600 000 IU mL−1 ( P = 0.02) were the baseline parameters significantly associated with lack of SVR, whilst positive serum HCV-RNA at week 12 was the only parameter independently associated with NR (100% negative predictive value). Conclusion. Full-dose antiviral therapy with PEG-IFN and ribavirin can be safely carried out even in patients with compensated, fully established cirrhosis and portal hypertension. Selecting patients on the basis of HCV genotype and viral load, and application of on-treatment stopping rule may help rationalize treatment in patients who are unlikely to obtain SVR. [ABSTRACT FROM AUTHOR]

In patients with liver disease, thrombocytopenia is a clinical feature that may represent an obstacle to invasive diagnostic or therapeutic procedures, chemotherapy, and anti-viral treatment. Stimulation of the bone marrow is the most promising therapeutic intervention for thrombocytopenia in patients with chronic liver disease. The description of thrombopoietin and its (de)regulation in patients with chronic liver disease have disclosed new treatment opportunities. Indeed, pharmacologic treatment options for thrombocytopenia can be divided into treatments targeted at the thrombopoietin receptor (synthetic thrombopoietins and thrombopoietin-mimetic agents), and use of cytokines with general thrombopoietic potential. Unfortunately, use of synthetic thrombopoietin was hampered by the development of neutralizing antibodies, and thrombopoietin mimetic agents have not yet entered clinical studies. Interleukin-11 proved to be useful in increasing platelet count in patients with chronic liver disease, although its use is limited by side-effects. Erythropoietin has shown promising results in improving thrombocytopenia in cirrhotic patients. In patients with chronic liver disease, safe and well-tolerated treatments aimed at improving thrombocytopenia are still lacking. Larger studies are needed to evaluate and better characterize the thrombopoietic potential of erythropoietin. Human studies with thrombopoietin-mimetic agents are eagerly awaited in order to assess both effectiveness and safety of these drugs. [ABSTRACT FROM AUTHOR]

Background Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. Aims To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as ‘rescue’ treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. Methods Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. Results The 7-day RLT achieved 84% (95% CI: 69–93%) and 86% (95% CI: 72–95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69–93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. Conclusions In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the polymorphism in elderly chronic hepatitis C patients treated with pegylated-interferon and ribavirin by G. Fattovich and colleagues in the 2011 issue.

Thrombocytopenia is likely the most common haematological abnormality that can be diagnosed in patients affected by chronic liver disease. In these patients, the presence of thrombocytopenia may have significant clinical implications. In fact, it can be a limiting factor when considering invasive procedures and may hamper the outcome of antiviral therapy with interferon. The prevalence of decreased platelet count in patients with chronic hepatitis C has been assessed in various studies that evaluated heterogenous patient populations and used various platelet count threshold to identify thrombocytopenia. This review shows that the prevalence of thrombocytopenia in these patients is variable and mainly depends upon the severity of the underlying liver disease and the criterion used to identify this haematological abnormality. Furthermore, the results of this epidemiological review provide an indirect evidence that confirms the multiplicity of aetiological factors underlying the pathophysiology of thrombocytopenia in chronic hepatitis C patients. Lastly, this study shows that up to 25% of patients treated with interferon may develop some degree of thrombocytopenia, and this may be associated with decreased sustained virological response rates. [ABSTRACT FROM AUTHOR]

The author reflects on factors that help improve the liver disease-related prognosis in patients with human immunodeficiency virus (HIV) infection. He cites the study by Pinato et al. on the prognostic utility of albumin-bilirubin (ALBI) grade. The author believes on the importance of estimated prognosis and assessment between prognostic factors and clinicopathological characteristics of HIV patients with HCC.

In this article, the authors, respond to comments made by some researchers, on their research related to gastroenterology. Authors says that as a general rule, a surrogate marker for a given variable, that is, presence/absence of oesophageal varices, that already has a definite diagnostic procedure, that is, endoscopy, should fulfil two major criteria. Firstly, it should be the product of a thorough statistical analysis and secondly, but no less importantly, it has to be biologically plausible. They further say that they have proposed a new evaluation tool and called for validation of proposed method, being conscious that only differences in opinion that arise from results obtained in well conducted studies contribute to scientific progress.

Presents letter to the editors on the usefulness of 13C-galactose breath test for the measurement of liver function.

Presents a letter the editor about the natural history of untreated intermediate stage hepatocellular carcinoma.

This article discusses the management and surveillance guidelines for Branch Duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN), a type of pancreatic lesion. The study aimed to determine the rates of malignant degeneration of these lesions and identify associated risk factors in order to propose a more cost-effective surveillance strategy. The study found that IPMN developed malignant degeneration in 3.3% of cases, with risk factors including the presence of High-Risk Stigmata (HRS), Worrisome Features (WF), and cyst size. Based on these findings, the study proposed a new surveillance strategy that maintained diagnostic accuracy while reducing costs. [Extracted from the article]

This article, published in the journal Endoscopy, examines the adherence to international guidelines in the management of Branch Duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN). The study collected data from four tertiary centers in Northern Italy from 2017 to 2023 and analyzed factors influencing non-compliance with the guidelines. The results showed that 54% of patients received recommendations that deviated from the guidelines, with a majority of these deviations being in an aggressive direction. While divergent strategies did not lead to different rates of IPMN-related mortality, they did result in increased surveillance costs compared to following the recommended guidelines. [Extracted from the article]

A letter to the editor is presented in response to the article "Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease" in the previous issue is presented.

Background In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free ( P = 0.02) and by IFN-based ( P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based ( P = 0.49) strategies. Conclusion In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. [ABSTRACT FROM AUTHOR]

Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. Conclusions Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. Aim To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. Methods A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alphafetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. Results Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/ terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. Conclusions Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients. [ABSTRACT FROM AUTHOR]

Background: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time.Methods: Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered.Results: In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%.Conclusions: CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis. [ABSTRACT FROM AUTHOR]

Background:Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time.Methods:Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered.Results:In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml−1 (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml−1 or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml−1 (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%.Conclusions:CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 1000-1006 Summary Background Abnormal intestinal clearance is involved in the pathogenesis of small intestinal bacterial overgrowth (SIBO). It is known that partially hydrolysed guar gum affects intestinal motility. Eradication therapy of SIBO is based on antibiotic treatment: no data are available on the role of fibre supplementation in eradicating SIBO. Aim To assess whether the combination of partially hydrolysed guar gum and rifaximin is more effective than rifaximin alone in the treatment of SIBO. Methods A 50 g-glucose breath test was given to 500 consecutive patients. Patients with a positive glucose breath test and predisposing conditions to SIBO entered into the study, and were randomized to receive rifaximin 1200 mg/day or rifaximin 1200 mg/day plus partially hydrolysed guar gum 5 g/day for 10 days. Patients completed a symptom questionnaire and glucose breath test both in basal condition and 1 month after withdrawal of therapy. Results Seventy-seven patients had SIBO. Eradication rate of SIBO was 62.1% in the rifaximin group (both on per-protocol and intention-to-treat analyses), and 87.1% (per-protocol, P = 0.017) and 85.0% (intention-to-treat, P = 0.036) in the rifaximin-plus-partially hydrolysed guar gum group. Clinical improvement was observed in 86.9% and 91.1% of eradicated cases in rifaximin and rifaximin-plus-partially hydrolysed guar gum groups respectively ( P = 0.677). Conclusion The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone. [ABSTRACT FROM AUTHOR]

The article reports on hepatobiliary and pancreatic, and also discusses cause of portal hypertension.