Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

Background: Unexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy. Aims: We evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting. Methods: In this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score. Results: In patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05\u20135.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85\u20131.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01\u20131.09) was significantly associated with a risk of recurrence. Conclusion: ALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs

Imbalance of Neutrophils and Lymphocyte Counts Can Be Predictive of Hepatocellular Carcinoma Occurrence in Hepatitis C-related Cirrhosis Treated With Direct-acting Antivirals

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Management of Delta Hepatitis 45 Years after the Discovery of HDV

In 1977 the viral Delta agent was discovered and subsequently characterized as the hepatitis Delta virus (HDV). HDV infection is associated with HBV infection since the defective HDV needs HBV to infect and replicate in the liver. Even if not a frequent cause of chronic liver disease, HDV infection is responsible for an aggressive progression of hepatitis towards advanced liver disease. At present, no FDA approved treatment exists for this specific form of hepatitis. Interferon alfa has been recommended as off-label therapy by major scientific societies (AASLD, EASL and APASL) and has proved effective in about one quarter of patients. In recent years, new therapeutic approaches have been studied, and EMA has approved a new drug (bulevirtide) for Delta hepatitis. In this review, we encompass the 45-year journey of managing Delta hepatitis and address the most recent developments in treating this severe and aggressive liver disease

Role of amantadine and other adjuvant therapies in the treatment of hepatitis C

There is room for improvement in the treatment of chronic hepatitis C with standard interferon (IFN) alfa. In the search for treatment adjuvants, the antiviral compound ribavirin has been found to significantly increase sustained virological response. Despite this improvement, the rate of "cure" remains low at approximately 40%, thus stimulating the search for additional adjuvants. In 1997, it was suggested that amantadine monotherapy could be used successfully to treat patients with chronic hepatitis C who had previously failed IFN alfa therapy, but ensuing studies could not support these findings. Instead, researchers have studied amantadine as an adjuvant to either IFN alfa alone or IFN alfa plus ribavirin, and promising results have been published. In this article, the author reviews the role of amantadine alone or as part of combination therapy regimens for chronic hepatitis C and briefly looks at the use of other agents as potential adjuvants

De modo quo ecclesiæ cum republica nexum considerare deceat, commentatio; quam, venia ampliss. fac. phil. Ups. præside doct. Dan. Boëthio ... pro gradu philosophico publico examini submittit Johannes Petrus Eurén. Bothniensis. In audit. Gust. maj. die II Apr. MDCCCIII. h. a. m. s.

Direct antiviral therapy has dramatically changed our possibility to eradicate hepatitis C virus (HCV) infection in all stages of chronic liver disease, with sustained virological response rates well above 90%. HCV eradication should lead to a better prognosis even after cirrhosis has established, including a reduced risk of developing hepatocellular carcinoma (HCC). Unfortunately, during the last two years different reports have raised the concern about a possible increased risk of developing HCC in cirrhotic patients treated with direct antivirals. In this review, we have evaluated the principal published data and have reached a few conclusions: (1) direct antiviral therapy does not seem to increase the cumulative annual rate of HCC de novo occurrence or recurrence; (2) direct antiviral therapy seems to accelerate the development of HCC, soon after the end of treatment, in those patients at higher risk of HCC occurrence or recurrence; and (3) preliminary reports seem to indicate that HCC developed after direct antiviral therapy has more aggressive features. These findings clearly indicate the need for aggressive and close monitoring of cirrhotic patients during and after antiviral treatment, to detect and treat HCC at their earliest occurrence

Ribavirin for chronic hepatitis C: And the mystery goes on

Twenty years ago, ribavirin was first used in the treatment for chronic hepatitis C. After few years, ribavirin, in combination with interferon-alpha, showed a dramatic synergistic efficacy against hepatitis C virus infection, leading to viral clearance in about 50% of patients. Recent discovery of potent inhibitors of hepatitis C virus proteases did not replace ribavirin as the mainstay of combination therapy for chronic hepatitis C. Despite this fundamental role of ribavirin, many aspects of the mechanism of action and of the optimal dose and duration of therapy remain to be discovered or settled. In the present review, the authors recall the milestones in the history of ribavirin and try to shed light on the more relevant features of ribavirin action and utilization, and on the clinical problems encountered in managing and optimizing treatment for chronic hepatitis C. Finally, some potential off-label use of this drug in most difficult-to-treat subjects is pointed out. In conclusion, even if a sort of mystery surrounds ribavirin, its efficacy against hepatitis C virus infection fortunately remains lasting and stable

Reactivation of Crohn's disease after pandemic aH1N1 and seasonal flu vaccinations.

We report a case of a prompt reactivation of a quiescent Crohn's disease with pain, fever and abdominal abscess which occurred after seasonal and pandemic flu vaccinations. Based on the clinical history and the timing of the events, we could relate the relapse of CD to the double vaccinations

Significance of IgM antibody to hepatitis C virus in patients with chronic hepatitis C

We assessed the correlation between the positivity for serum IgM antibody to hepatitis C virus and the activity of liver disease in patients with chronic hepatitis C virus infection. Serum samples were taken from 10 antibody to hepatitis C virus‐positive asymptomatic patients with normal serum ALT levels, from 14 untreated patients with clinically and histologically proven chronic hepatitis C and from 26 patients with clinically and histologically proven chronic hepatitis C assigned to receive recombinant interferon α‐2a (6 million IU three times a week for 6 mo). Each serum specimen was tested for IgM antibody to hepatitis C virus‐associated C 100‐3 antigen by enzyme‐linked immunosorbent assay. Patients were observed for at least 12 mo. All 10 patients with normal ALT values tested negative for IgM antibody to hepatitis C virus. In contrast, 33 of 40 (82%) patients with chronic hepatitis C had IgM antibody to hepatitis C virus, and a positive correlation was seen between the ALT level and the level of IgM antibody to hepatitis C virus (r = 0.803, p < 0.001). During interferon treatment, ALT levels declined into the normal range in 18 of 26 treated patients (69%) and remained normal after stopping treatment in 8 patients (31%). In untreated patients, in treated patients who did not respond to interferon treatment and in responder patients who relapsed, no significant changes in IgM antibody to hepatitis C virus levels were seen during the study period. In contrast, IgM antibody to hepatitis C virus became undetectable by the end of interferon treatment in seven of eight patients with a sustained response. In conclusion, we found a positive correlation between the presence of serum IgM antibody to hepatitis C virus and the activity of the hepatitis C‐induced liver disease. In patients with chronic hepatitis C showing a response to α‐interferon treatment, the disappearance of IgM antibody to hepatitis C virus predicted that the response would be sustained. (HEPATOLOGY 1992;15:998–1001). Copyright © 1992 American Association for the Study of Liver Disease