A compact evolved antenna for 5G communications.

Flexible and bendable electronics are gaining a lot of interest in these last years. In this scenario, compact antennas on flexible substrates represent a strategical technological step to pave the way to a new class of wearable systems. A crucial issue to overcome is represented by the poor radiation properties of compact antennas, especially in the case of flexible and thin substrates. In this paper, we propose an innovative design of a miniaturized evolved patch antenna whose radiation properties have been enhanced with a Split Ring Resonator (SRR) placed between the top and the ground plane. The antenna has been realized on a flexible and biocompatible substrate polyethylene naphthalate (PEN) of 250 µm by means of a new fabrication protocol that involves a three-layer 3D-inkjet printing and an alignment step. The antenna has been characterized in terms of the scattering parameter S11 and the radiation pattern showing a good agreement between simulations and measurements.

Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis.

BACKGROUND: It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. AIM: To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. METHODS: A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. RESULTS: Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6-82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8-80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4-89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4-89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. CONCLUSION: The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

HBsAg kinetics in chronic hepatitis D during interferon therapy: on-treatment prediction of response.

BACKGROUND: Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed. AIM: To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD). METHODS: Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR). RESULTS: In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker. CONCLUSIONS: A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment.

Long-term outcome of hepatitis B virus-related Chronic Hepatitis under protracted nucleos(t)ide analogues.

Long-term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti-HBe-positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV-DNA clearance, add-on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow-up were the main endpoints, as the complication-free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV-DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV-DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow-up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10-year event-free survivals were, respectively, 89.3% (95% CI, 81.7 -96.9) and 75.6% (95% CI, 61.5 -89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 -84.1) and 40.4% (95% CI, 16.9 -63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronic HBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.

Variations of serum levels of adiponectin and resistin in chronic viral hepatitis.

BACKGROUND AND AIMS: Several studies investigated the possible role of adipokines during chronic viral hepatitis, not producing defined results neither clearly establishing their behavior in course of anti-viral treatment. Our study evaluated blood concentrations of adiponectin and resistin in patients with chronic hepatitis C (CHC), B (CHB), and D (CHD) receiving anti-viral treatment, at baseline and after therapy. METHODS: We examined 122 subjects, divided into two groups: 64 patients with chronic hepatitis C virus (HCV) infection (38 males and 26 females, mean age 47.25 yr) and 58 patients including 39 ones with chronic hepatitis B virus (HBV) infection (26 males and 13 females, mean age 48.46 yr) and 19 ones with chronic HBV-hepatitis D virus (HDV) infection (15 males and 4 females, mean age 45.79 yr). Serum levels of adiponectin and resistin were assayed by enzyme-linked immunosorbent assay. RESULTS: In the group of CHC patients we observed a significant decrease in resistin after therapy (p=0.006), while not a significant increase in adiponectin after treatment (p=0.32). Evaluation of changes in adiponectin and resistin levels after anti-viral treatment, both in responders and non-responders, revealed no significant variations. In the group of HBV+ and HBV-HDV+ patients, we found a decrease in resistin after therapy (p=0.0016) and a not significant reduction in adiponectin after treatment (p=0.13). Furthermore, we noticed a significant reduction of resistin (p=0.006) in the sub-group of responders. CONCLUSIONS: Our data suggested the possible marker role of adiponectin and resistin in the inflammatory process in course of chronic viral hepatitis.

Estimates of HCV-1 patients attaining RVR following dual therapy with peg-interferon and ribavirin.

BACKGROUND: Given the significant side-effects and healthcare costs associated with telaprevir- or boceprevir-combination therapy, identifying patients likely to respond to dual therapy peg-interferon (Peg-IFN)/ribavirin is highly desirable. Since the perception of how large the pool of patients who may achieve rapid virologic response (RVR) is vaguely ascertained, we searched the literature for this information. METHODS: Studies on patients treated with Peg-IFN/ribavirin were identified by searching MEDLINE and analyzed by meta-analysis. The primary end point was weighted estimates of RVR. The influence on race/ethnicity, baseline viremia, type of Peg-IFN, ribavirin dosage, and significant hepatic fibrosis on the results was evaluated. RESULTS: Across 38 studies on 13,219 patients, the fraction of RVR patients was 19.6 %. The only baseline factor influencing RVR was race/ethnicity, with higher rates in Asian (26.7 %) and Caucasian patients (22.5 %). Of the 1,735 RVR patients, 85.1 % attained sustained virologic response (SVR). In these, SVR was influenced by ribavirin dose (86.8 vs. 72.8 % for high or low), type of Peg-IFN (91.8 % for alpha-2b vs. 82.9 % for alpha-2a), and treatment duration (91.7 % for 48 weeks vs. 79.4 % for 24 weeks). CONCLUSIONS: One fifth to one fourth of hepatitis C virus genotype 1 (HCV-1) patients can be safely treated with dual therapy of Peg-IFN/ribavirin, and may be spared from cost and inconvenience of regimens considering the addition of HCV protease inhibitors.

Unawareness of HBV infection among inpatients in a Southern Italian hospital.

Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV-related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen-positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25,000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them (98%) being anti-HBe positive. HCV and HDV co-infections were ascertained in 2.9% and 0.6% of cases, respectively. Two hundred and fifty-three subjects (81%) agreed to undergo further investigation, 132 of them (52%) were HBV-DNA positive. One hundred and two patients (40.3%) were unaware of their infection; this was encountered among 29% of HBV-DNA-positive and 52% of HBV-DNA-negative subjects (P < 0.01). Subjects already aware of their infection were more likely to present with abnormal alanine aminotransferase (ALT) levels (27%vs 15%), serological presence of HBV-DNA (63.6% vs. 36%) and liver cirrhosis (30%vs. 13%). A high proportion of HBsAg-positive patients (40.3%) were unaware of their infection, which had evolved to the stage of liver cirrhosis in a consistent percentage of them.

Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patients.

BACKGROUND: Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis. AIMS: To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients. METHODS: A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 microg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively. RESULTS: Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0-217.3), 4.2 (95% CI 1.2-15.3) and 9.1 (95% CI 2.2-38.0), respectively. CONCLUSION: In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.

Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis.

INTRODUCTION: Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease. AIM: To investigate factors potentially preventing atherosclerosis in PBC patients. METHODS: Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 +/- 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome. RESULTS: The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 +/- 50.5 mg/dL in PBC vs 221.7 +/- 39.7 mg/dL in NASH vs 209.8 +/- 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase. CONCLUSIONS: The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

The use of molecular assays in the management of viral hepatitis.

Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients' needs and physicians' objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only "home brew" methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.

Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: a pilot study.

BACKGROUND: In chronic hepatitis B, long-term use of alpha interferon is hampered by side effects, and long-term treatment with nucleos(t)ide analogues is burdened by drug-resistant mutants. We hypothesized that alternate rounds of lamivudine and alpha interferon might circumvent previous shortcomings. AIM: To evaluate efficacy of sequential lamivudine or IFN-alpha2b monotherapies in preventing occurrence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants and achieving virological and biochemical response. METHODS: Fifteen patients with hepatitis B surface antigen, anti-HBe-positive chronic hepatitis received four consecutive rounds of monotherapy with lamivudine (100 mg/day), IFN-alpha2b (5MU/tiw), lamivudine, IFN-alpha2b. Serum HBV-DNA levels were evaluated during and off treatment, HBV polymerase and pre-core/core regions sequenced. RESULTS: End-of-treatment response was achieved in 10 patients (67%). One patient did not respond, a second developed genotypic resistance at week 24. A rebound in viremia occurred in three patients at week 48. Six patients (40%) remained sustained responders. Triple promoter mutations at nucleotides 1762-1764-1896 prevailed in non-responders (60%) as compared to responders (20%). L180M/M204V mutations were identified during virological breakthrough. CONCLUSION: Sequential approach of alternate rounds of lamivudine or interferon may help patients to tolerate a prolonged schedule of therapy and protect them from emergence of viral strains.

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study.

BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre-Hepatitis C era' and data on the natural history are still incomplete. AIM: To evaluate the clinical presentation and the natural history of type I AIH. METHODS: Seventy-three consecutive patients with a regular follow-up of at least 2 years were prospectively included in the study. The mean follow-up was 91 +/- 61 months. RESULTS: Patients with 'acute' onset at presentation were significantly older than patients with 'chronic' onset (P < 0.05) and had significantly higher serum levels of transaminase, gamma-glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow-up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow-up, but seven patients were transplanted. The cumulative transplant-free probability of survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.

Ultrasonographic and biochemical parameters in the non-invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis.

BACKGROUND: Prior studies suggest that platelet counts of <140 000/microL can discriminate patients with different stages of fibrosis. AIM: To determine the added value of abdominal ultrasound analysis of morphological liver features in increasing the diagnostic accuracy of platelet counts for the prediction of liver fibrosis at histology. METHODS: In a retrospective study, clinical records of 1143 chronic hepatitis C patients at their first presentation, naives to both liver biopsy and anti-viral treatment, were reviewed. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of following indices were evaluated singularly or in combination: platelet counts <140 000/microL; nodular liver surface, spleen and portal vein size. RESULTS: All indices had specificity rate of > or =90% in excluding bridging fibrosis/cirrhosis, whereas sensitivity was acceptable (51%) for only platelet counts <140 000/microL. None of the ultrasonographic parameters singularly evaluated and reached an acceptable sensitivity rate. For ruling cirrhosis in or out, specificity rate was > or =82% for all tests, with the highest value reported by portal vein size. Low platelet counts plus nodular liver surface had the best sensitivity. CONCLUSIONS: No additional significant predictive value was given by adding ultrasonographic parameters to low platelet counts, whereas only a mild non-significant improvement in sensitivity was obtained combining platelet counts <140 000/microL with the presence of nodular liver surface. The platelet counts <140 000/microL showed the best predictive value for including both significant fibrosis and cirrhosis.

Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study.

BACKGROUND: Delta virus (HDV)-related chronic hepatitis is difficult to treat. AIMS: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion. METHODS: Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT > or = 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks. RESULTS: Twenty-five patients (81%) completed the study. No patient was HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B surface antigen without seroconversion. Paired pre-treatment and week 104 liver biopsies were available from 19 patients: of which three of seven (43%) from group A and two of 12 patients (17%) from group B had a > or =2 point decrease in the Ishak necroinflammatory score. CONCLUSION: A sustained complete response was achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and a partial histological response in 26% of them. Hepatitis D virus viraemia was unaffected, even in patients when hepatitis B virus replication was lowered by lamivudine therapy.

Treatment of hepatitis D.

Delta virus related chronic hepatitis is difficult to treat. The response to alpha-interferon (IFN), which still represents the only therapy for chronic hepatitis D, varies widely and occurs at different times from the beginning of treatment. The rate of response is proportional to the dose of IFN, with 9 million units (MU) three times a week being more effective than 3 MU thrice weekly. Sustained responses are unusual and are accompanied by the clearance of serum hepatitis B virus surface antigen (HBsAg), seroconversion to anti-HBs and improvement of liver histology. Although disease of a short-standing may respond better to therapy, clear predictors of response are still unidentified. Besides IFN, other therapeutic approaches such as immunosuppressive drugs, acyclovir, ribavirin and thymosin, have been unhelpful. Available evidence does not support the use of deoxynucleotide analogues. Famciclovir has no effect on disease activity and hepatitis D virus (HDV)-RNA levels. Twelve- or 24-month lamivudine treatment does not significantly affect biochemical, virological or histological parameters. Pegylated-IFN could represent a reasonable therapeutic option in the long-term treatment required for chronic hepatitis D. Antisense oligonucleotides and prenylation inhibitors hold promise as therapeutic agents of the future. Liver transplantation provides a valid option for end-stage HDV liver disease; the risk of re-infection is lower for HDV than for HBV under long-term administration of hyperimmune serum against HBsAg. Molecularly tailored drugs capable of interfering with crucial viral replicative processes of HDV appear to be the best prospect in the treatment of hepatitis D.

Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B.

AIM: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. METHODS: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. RESULTS: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. CONCLUSION: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

Re-treatment of patients with anti-HBe-positive chronic hepatitis B who relapsed after an initial course of lamivudine.

AIM: To evaluate the efficacy of a long-term course of lamivudine monotherapy in patients with anti-HBe-positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2). METHODS: Biochemical and virological tests were performed every 3 months. At baseline and breakthrough, the region coding for the YMDD amino acid motif was sequenced. RESULTS: The length of re-treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4% and 48.6% at 6, 12 and 24 months, respectively. By the second year, responders amounted to 62.5% and 40% in Groups 1 and 2, respectively (P = 0.10). The 18 responders at month 24 are still on therapy after 25-51 months of treatment: 14 still maintain a response, nine from Group 1 and five from Group 2. CONCLUSIONS: Re-treatment with lamivudine can control viral replication. This effect is maintained for the initial 12 months in two-thirds of patients, but afterwards the duration of response lessens due to the development of viral resistance.