Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.

Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

We studied 648 hepatitis B surface antigen (HBsAg)– and/or anti-hepatitis C virus (HCV)–positive patients to evaluate the virologic and clinical characteristics of multiple hepatitis viral infection. We defined as Case B–C an HBsAg/anti–HCV positive patient and as Case b–C an anti–HCV/anti–HBc–positive, HBsAg/anti–HBs-negative patient. For each Case B–C we scheduled as Control–B an HBsAg positive and anti–HCV negative patient and as Control–C an HBsAg/anti–HBs/anti-hepatitis B core antigen (HBc)–negative and anti–HCV-positive patient. Control group C was used as the control also for Case group b–C. Serum HBV DNA by molecular hybridization was found more frequently in Control group B (54% of 161 patients) than in Case group B–C (35.7% of 84, P < .01). The prevalence of HBV wild type was similar in Case group B–C (14.3%) and in Control group B (17.4%), whereas the e–minus strain was less frequent in Case group B–C (10.7% vs. 33%; P < .01). HBV DNA by polymerase chain reaction (PCR) was detected in 40.8% of 71 patients in Case group b–C. HCV RNA was detected more frequently in Control group C (90.7% of 130 patients) than in Case group B–C (65.2% of 69, P < .0001). Moderate or severe chronic hepatitis or cirrhosis were more frequent in Case group B–C (62.9% of 65 patients) than in Control group B (46.7% of 90, P < .05) or C (40.8% of 98, P < .005), and in Case group b–C (71.1% of 76) than in Control group C. Thus, in multiple hepatitis we observed a reciprocal inhibition of the viral genomes and a more severe liver disease. In Case group b–C, serum HBV DNA was frequent and the clinical presentation was severe.

The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.