non-A, non-B Research Articles

Zone Zero Hybrid Repair of the Thoracic Rupture of a False Lumen in Non-A Non-B Aortic Dissection

Zone Zero Hybrid Repair of the Thoracic Rupture of a False Lumen in Non-A Non-B Aortic Dissection

Aortic Outcome after Implementation of a Treatment Strategy for Type B Aortic Dissection Involving the Aortic Arch

ObjectiveTo evaluate outcomes achieved after implementing a treatment strategy for non-A non-B (NANB) (B 1-2 D according to the latest consensus document of the Society of Vascular Surgery (SVS) and Society of Thoracic Surgeons (STS) acute aortic dissection (AAD). MethodsThis retrospective observational study adhered to the STROBE checklist. All cases of NANB AAD (B 1-2 D) treated at our Institution between January 2016 and December 2022 were reviewed. Morbidity, mortality, aortic-related reintervention, and remodelling were analysed. ResultsAmong 519 cases of acute aortic syndrome, n=22 (4.2%) patients presented with NANB AAD (B 1-2 D) (n=16,72.7% men, mean age 61.5 years+/14.7). Eleven cases were managed with best medical treatment (BMT) alone. Among them, one patient (9.1%) died suddenly two days after diagnosis for aortic rupture. Frozen elephant trunk procedure (FET) was required in the remaining 11 patients: 7(31.8%) needed emergent operation for risks of impending aortic rupture/retrograde AD extension and 4(26.7%) underwent delayed surgery within a month from initial presentation. Overall, in-hospital mortality was 9.1% with both FET and BMT. At a median follow-up of 40 months (range 2 days-200 months) no other deaths occurred. A statistically significant differences in the rate of FL thrombosis (100% vs 55.5%, p=.033) and a significant positive aortic remodelling in zone 3 (p<.001) and 4 (p=0.038) were reported in operated versus medically managed patients. ConclusionThe best treatment for NANB is not established. We advocate for medical stabilisation with an operative approach that favours open surgery in the acute post dissection period, promotes aortic remodelling and carries acceptable risk in centres where FET is performed routinely.

Challenges in Diagnosis of Non-A Non-B Acute Aortic Dissection

ObjectiveNon-A non-B (NANB) aortic dissections are uncommon and frequently unrecognized diseases.However, their proper identification is crucial given the unpredictable behaviour of the dissected aorta with potential mortality and increased morbidity. We investigate the accuracy of radiological computed angio-tomography (CTA) reports in the diagnosis of acute NANB and the risk related to delayed recognition or misdiagnosis. MethodsThe pre-treatment contrast CTA of all consecutive patients admitted with acute aortic dissection (AAD) in a University Hospital in London (UK) between January 2017 and May 2023 were reviewed to retrospectively verify the accuracy of CTA reports in the diagnosis of NANB AAD (B1-2D The risk related to the delayed diagnosis (morbidity, mortality, and hospital re-admissions) were evaluated as secondary outcomes. The study was conducted according to the STROBE guidelines. ResultsOverall, 588 aortic CTAs were reviewed for a total of n=393 (66.8%) type A AADs, n=171 (29%) type B AADs and n=25(4.3%) NANB AADs (n=16, 64% men, mean age 60.56, DS+/- 14.6 years). While no case of misdiagnosis was identified in Type A or B AAD groups, in NANBs only about a third of cases (n=9, 36%) were immediately indicated as “NANB” (n=2, 8%) or “B with retrograde extension into the arch” (n=7, 28%), n=8 cases (32%) were described generically as “arch dissections” (n=6, 24%) or “type A and B” AAD (n=2, 8%). The remaining 32% of patients received a diagnosis that did not include mention of the arch, as n=6(24%) cases were reported to be “type A” and n=2(8%) to be “type B” AADs. Despite the heterogeneity of terms used to describe NANB AAD, no case of cardiac tamponade, new onset malperfusion nor neurological complications were reported, and no sudden death nor home-discharge and readmission while waiting for the proper diagnosis. ConclusionThe heterogeneity of terms used to describe NANB aortic dissection highlights the need for increased awareness, adoption of in guideline based classification systems, and further education to better understand and correctly address this challenging entity, minimizing misdiagnosis in ambiguous or difficult cases.

Differences in In-Hospital and Follow-Up Outcomes Between Non-A Non-B Aortic Dissection and Type B Aortic Dissection Treated by Endovascular Based Treatment.

Non-A non-B aortic dissection (AD) is a rare and life-threatening medical emergency, and it has been controversial whether it should be managed as type B aortic dissection (TBAD). The study aims to compare in-hospital and follow-up outcomes between patients with non-A non-B AD and those with TBAD treated by endovascular based treatment (EBT). From January 2017 to December 2021, 96 consecutive patients with non-A non-B AD met the inclusion criteria and underwent EBT. Patients with TBAD were matched to patients with non-A non-B AD at a 1:1 ratio using propensity score matching analysis to correct for baseline confounding factors. The primary endpoint was all-cause mortality. Aortic-related events were defined as dissection-related death, aortic rupture, retrograde type A aortic dissection, reintervention, and type Ia endoleak. Patients with non-A non-B AD required more TEVAR-related adjunctive procedures compared to TBAD patients during EBT and they required a longer ICU length of stay (36.0 vs 24.0 hours, P < .05) as well as a longer hospitalization (8.0 vs 7.0 days, P < .05) after EBT. There was no statistical difference in overall survival after EBT for patients with TBAD and non-A non-B AD. However, compared to patients with TBAD, non-A non-B AD patients had a higher rate of reintervention and experienced more aortic-related late events during follow-up. Patients with non-A non-B acute AD who are treated with EBT do not have higher in-hospital or follow-up mortality rates compared to patients with type B AD. However, there is an increased risk of reintervention and aortic-related late events after the intervention during follow-up.

Non-A Non-B Acute Aortic Dissection: Is There Some Confusion in the Radiologist's Mind?

The aim of this study is to define and determine the rate of acute non-A-non-B aortic dissections, and to evaluate CT angiography findings and possible complications, as well as to discuss management strategies and currently available therapy. Non-A non-B type of aortic dissection is still a grey area in the radiologist's mind, such that it is not entirely clear what should be reported and completed in terms of this disease. A retrospective single-center study including 36 pre-treatment CT angiograms of consecutive patients (mean age: 61 years) between January 2012 and December 2022 with aortic dissection involving the aortic arch with/without the thoracic descending/abdominal aorta (type non-A non-B). According to the dissection anatomy, we identified three modalities of spontaneous acute non-A-non-B anatomical configurations. Configuration 1 (n = 25) with descending-entry tear and retrograde arch extension (DTA entry). Configuration 2 (n = 4) with Arch entry tear and isolated arch involvement (Arch alone). Configuration 3 (n = 7) with Arch entry and anterograde descending (±abdominal) aorta involvement (Arch entry). CT angiogram findings, management, and treatment options are described. Acute non-A non-B dissection represents an infrequent occurrence of aortic arch dissection (with or without involvement of the descending aorta) that does not extend to the ascending aorta. The complete understanding of its natural progression, distinct CT angiography subtypes, optimal management, and treatment strategies remains incomplete. Within our series, patients frequently exhibit a complex clinical course, often necessitating a more assertive approach to treatment compared to type B dissections.

Acute aortic dissection: Clinical characteristics and outcomes

Background: Acute aortic dissection (AAD) is a serious emergency. This prospective study aims to reveal the clinical characteristics and outcomes of medical and surgical treatments of AAD at the Ibn Al-Bitar Cardiac Centre. Methods: Over a 30-month period ending on Feb 27, 2019, 33 patients (27 males) admitted within 14 days after the onset of AAD symptoms were enrolled. The diagnosis was based on clinical findings and was confirmed by echocardiography and/or CT aortography. Intensive medical therapy was immediately initiated. Stanford classification was applied. Uncomplicated type B aortic dissections (AD) were managed conservatively while complicated type B and all type A dissections were referred for surgery. Perioperative data were entered into a Microsoft Excel-designed database, and the results were collected and statistically analyzed. Results: The male-to-female ratio was 9:2. The age range was 22–75 years, with a mean age of 48.8 ± 13.9 years. The main risk factors were hypertension (66.66%), smoking (42.42%), and Marfan’s syndrome (15.15%). In 84.84% of the cases, chest pain was the presenting symptom. CT aortography revealed dissection of the thoracic aorta in 91% of the cases and the abdominal aorta in 51.5% of the cases. A total of 24 (72.7%) patients had type A AD, and 7 (21.2%) patients had type B AD, whereas two (6.1%) had Non-A Non-B categories. Among those with type B AD, 71.42% had complications. For 48.5% of the patients, surgery was offered. The overall mortality rate was 48.5%, matching the rates that had been already published. Surgery had a lower mortality rate than medical treatment (37.5% vs. 62.5%). The mortality rate of type A was higher than type B (58.3% vs. 28.6%). Conclusions: Urgent surgery performed by expert surgeons is essential to save victims of AAD primarily type A dissection.

Management and Outcomes of Non-A Non-B Aortic Dissection

The results of best medical treatment (BMT), endovascular based treatment (EBT), and total arch replacement (TAR) with frozen elephant trunk (FET) treatment in a single centre experience were reported in non-A non-B aortic dissection patients. From January 2016 to May 2020, 215 consecutive patients with acute or subacute non-A non-B aortic dissection were enrolled. The primary endpoints were all cause death. Secondary endpoints included follow up adverse aortic event (AE), a composite of the outcomes of dissection related death, rupture, retrograde type A aortic dissection, stent graft induced new entry tear, secondary endoleak, and follow up re-intervention. Kaplan-Meier curves were used to evaluate associations between different treatments and outcomes. Among the 215 dissection patients, 127 (59.1%) received EBT, 42 (19.5%) received TAR+ FET, and the remaining 46 (21.4%) received BMT. Thirty day mortality was higher in patients receiving TAR+ FET (7.1%) than in those treated with EBT (1.6%) or BMT (2.2%) (p= .12). However, after a median follow up of 39.1 (27.0 - 50.7) months, no additional death was recorded in the TAR+ FET group, while nine (7.3%) patients died in the EBT group and 14 (31.8%) died in the BMT group (p < .001). Specifically, EBT and TAR+ FET showed no significant difference in midterm mortality rate, follow up AE, and re-intervention for complicated or uncomplicated dissection patients involving zone 2. For patients with uncomplicated non-A non-B aortic dissection involving zone 2, EBT could profoundly decrease the mortality rate, follow up AE and re-intervention when compared with BMT (p < .010 for all), although this difference was not statistically significant between TAR+ FET and BMT. No statistical comparison was performed in patients with zone 1 involvement because of the limited number of patients. It was demonstrated that EBT or TAR+ FET might be a viable strategy for non-A non-B aortic dissection patients.

The Results of the Use of the Technique of Switching the Vessels of the Aortic Arch in the Formation of the Avascular Zone of Stent-Graft Fixation in the Hybrid Treatment of Thoracic Aortic Aneurysms

Thoracic and aortic aneurysms, including Stanford type B and neither A nor B aneurysms, are a complex problem for cardiac surgery. For a long time, the treatment of this pathology was carried out through the open method, which was associated with high hospital mortality. Hybrid and endovascular treatment have significantly reduced the number of complications and improved in-hospital mortality, although such methods are associated with specific difficulties, the study and elimination of which is an urgent issue at the present stage of cardiac surgery.&#x0D; The aim. To analyze the immediate and first long-term results of treatment of type B and non-A non-B aortic dissection through the hybrid method with the formation of avascular zone of proximal fixation of the stent-graft in the aortic arch, i.e. “landing zone”.&#x0D; Materials and methods. For the period from January 1, 2016 to December 31, 2019 at the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine 122 patients underwent surgical treatment for type B and non-A nonB aortic dissection, of whom 57 (46.7%) patients underwent hybrid intervention involving the formation of a “landing zone”, i.e. an avascular section of the aortic arch to fix the stent-graft. Stent-graft was implanted in Z0 in 5 (8.8%) cases, in Z1 in 24 (42.1%) cases, and in Z2 in 28 (49.1%) cases. The stent-grafts used were Lifetech Ankura (41 cases), Relay (12 cases), and Medtronic Valiant (4 cases). The main causes of pathology were type B acute aortic aneurysm (11 [19%]), type B subacute aortic aneurysm (4 [7%]), type B chronic aortic aneurysm (30 [53%]), penetrating aortic ulcer (1 [2%]), primary parietal thrombosis of the aortic lumen (1 [2%]), postcoarctation aortic aneurysm (8 [14%]), thoracic aortic aneurysm (3 [5%]).&#x0D; Results. The total number of complications was 11 (19% of cases). Among the types of operations, the number of complications was evenly distributed, 5/28 (18%) were observed in partial debranching, 5/27 (19%) in subtotal debranching and 1/2 (50%) in total debranching. Hospital mortality was 3/122 (5.3%).&#x0D; Conclusions. The described methods of treatment of aneurysms of the arch and descending aorta have real prospects for development due to minimal invasiveness, reduction of the duration of surgery and time spent in the clinic, and significantly lower in-hospital mortality compared to traditional “open” surgery.

Early and Long-Term Follow-Up for Chronic Type B and Type Non-A Non-B Aortic Dissection Using the Frozen Elephant Trunk Technique.

Background: This study aimed to evaluate the early and long-term outcomes of a single center using a frozen elephant trunk (FET) procedure for chronic type B or non-A non-B aortic dissection.Methods: From February 2009 to December 2019, 79 patients diagnosed with chronic type B or non-A non-B aortic dissection who underwent the FET procedure were included in the present study. We analyzed operation mortality and early and long-term outcomes, including complications, survival and interventions.Results: The operation mortality rate was 5.1% (4/79). Spinal cord injury occurred in 3.8% (3/79), stroke in 2.5% (2/79), and acute renal failure in 5.1% (4/79). The median follow-up time was 53 months. The overall survival rates were 96.2, 92.3, 88.0, 79.8, and 76.2% at 1/2, 1, 3, 5 and 7 years, respectively. Moreover, 79.3% of patients did not require distal aortic reintervention at 7 years. The overall survival in the subacute group was superior to that in the chronic group (P = 0.047).Conclusion: The FET technique is a safe and feasible approach for treating chronic type B and non-A non-B aortic dissection in patients who have contraindications for primary endovascular aortic repair. The technique combines the advantages of both open surgical repair and endovascular intervention, providing comparable early and long-term follow-up outcomes and freedom from reintervention.

A RETROSPECTIVE OBSERVATIONAL STUDY TO DETERMINE ETIOLOGY IN PEDIATRIC PATIENTS WITH ACUTE LIVER FAILURE

Acute liver failure is a less common disease in pediatrics. Its outcome mostly depends on the etiology. With known etiology the outcome is favourable and with advancement of liver transplantation, the mortality is further reduced. Most of the study for etiology are from western countries , study conducted at our center in attempt to know the prevailing etiology for acute hepatic failure in our region. Materials and method: Retrospective observational study was done at Pediatrics Department, Katihar medical college, Katihar, Bihar, over the period from September 2017 to December 2020. 62 cases were selected by reviewing the les which qualied the inclusion and exclusion criteria. Information was taken on self designed questionnniare. Result and discussion: Most common identiable etiology comes out Hepatitis A (9.6%) and Hepatitis B (9.6%) followed by bacterial infection (8.1%), drug induced hepatitis (3.2%) and wilson's disease (3.2%). There was 2 cases of HAV with coinfection of staphylococcus and salmonella each. Majority of cases (30 out of 62 cases) were nonA nonB nonC viral hepatitis.

The Frozen Elephant Trunk Technique for the Treatment of Type B and Type Non-A Non-B Aortic Dissection

To evaluate outcomes of patients with acute complicated or chronic Type B or non-A non-B aortic dissection who underwent the frozen elephant trunk (FET) technique. Between April 2013 and July 2019, 41 patients presenting with acute complicated (n=29) or chronic (n=12) descending thoracic aortic dissection were treated by the FET technique, which was the treatment of choice when supra-aortic vessel transposition would not suffice to create a satisfactory proximal landing zone for endovascular aortic repair, when a concomitant ascending or arch aneurysm was present, or in patients with connective tissue diseases. One patient (2%) died intra-operatively secondary to an aortic rupture in dwnstream aortic segments. No post-operative deaths occurred. Four patients (10%) suffered a non-disabling posto-operative stroke and were discharged with no clinical symptoms (modified Rankin Scale [mRS] 0, n=1), no significant disability (mRS 1, n=2), or with slight disability (mRS 2, n=1). No spinal cord ischaemia was observed. The primary entry tear was either surgically resected or excluded from circulation in all patients. During follow up, one patient (2%) died after two years (not aorta related) and 16 patients (39%) underwent an aortic re-intervention after 7.7 [interquartile range 0.7, 15.8] months (endovascular aortic repair: n=14; open thoraco-abdominal aortic replacement: n=1, hybrid approach: n=1). The FET technique is an effective treatment option for acute complicated and chronic Type B or non-A non-B aortic dissection in patients in whom primary endovascular aortic repair is non-feasible. While the post-operative outcome is acceptable with a relatively low incidence of non-disabling strokes, this study also underlines the considerable need for aortic re-interventions. Continuous follow up of all patients undergoing the FET procedure is essential.

Acute Non-A Non-B Aortic Dissection: Definition, Treatment and Outcome

Acute Non-A Non-B Aortic Dissection: Definition, Treatment and Outcome

Evidence for the presence of autochthonous (locally acquired) cases of acute hepatitis E virus infections in Italy since the 80s

BackgroundAutochthonous (locally acquired) cases of acute hepatitis E virus have been recently reported in several developed countries. AimTo evidence cases, if any, and characteristics of acute hepatitis E virus infections in North-East of Italy several years ago. MethodsIn 2014, stored sera of 165 nonA–nonB acute hepatitis referred to the hospital of Padua during the period 1978–1991 were tested for hepatitis C virus antibodies by EIA III and for anti-hepatitis E virus IgM by Wantai HEV IgM ELISA. Anti-hepatitis E virus IgM positive sera were tested by Real Star HEV RT-PCR kit (Altona Diagnostics, Hamburg, Germany). ResultsNinety-six (58.1%) sera resulted anti-HCV positive, and thus classified as acute C hepatitis. None of these subjects was anti-HEV IgM positive. Out of the 69 anti-HCV negative cases, 4 (5.8%) resulted anti-HEV IgM positive (one case hepatitis E virus-RNA positive), with an increasing trend from 2.8% during the years 1978–1984 to 9.1% during the years 1985–1991. All cases occurred in Italian patients with no travel abroad history. ConclusionsThere is evidence for the presence of autochthonous cases of acute hepatitis E virus infections in Italy since 80s.

Global Eradication of Hepatitis C Virus: A Herculean Task

Once dubbed under the entity of Non A-Non B (NANB) hepatitis agents, Hepatitis C Virus (HCV) was finally discovered and named in 1989 [1,2]. HCV is an enveloped single stranded positive sense 9.6 kb RNA virus about 50 nm in diameter under the hepacivirus genus within the Flaviviridae family. Approximately 200 million people (about 3% of the world population) are currently infected with HCV including about 4 million in USA itself. The virus has 6 major genotypes and over 50 subtypes based on the genomic heterogeneity. Some experts recognize even more genotypes but it remains debatable until major genomic variability is authentically demonstrated in the new genotypes. While genotypes 1-3 have a worldwide distribution, some types are predominantly confined to certain geographical regions. Whereas type 1 is most prevalent in USA and Europe, type 3 in Southeast Asia, type 4 principally in Middle East, Egypt and Central Africa, the type 5 is almost exclusively encountered in South Africa. The prevalence rates of HCV infection vary from <1.5% in USA to 10% or more in Egypt. For reasons largely unknown, the baby boomers (people born between 1945 to1964) account for nearly three fourths of cases in most parts of the world. The major mode of HCV transmission has been variable over time. The main determinants had been the practice of parenteral drug abuse which was uncommon before 1960 and the development of HCV screening kits for blood, tissue or organ donors which became available only in early 1990s. Though globally, the major mode of transmission has usually remained unscreened blood/tissue/organ donors, the parenteral infective drug abuse may presently be the leading mode in most parts of the world including the developed countries. The other modes of transmission include the widespread practice of tattooing, use of unsterilized injection needles, vertical transmission from mother to child and the sexual contact. The incubation period is variable but on an average it is about 8 weeks. Only 15-25% individuals are able to clear the HCV infection spontaneously. Up to 85% infections may be asymptomatic. Majority of those infected develop chronic infection which runs for decades. The symptomatic HCV infection usually presents as mild disease with jaundice in less than 50% cases in whom the liver enzymes are either slightly elevated or even within normal range. If untreated chronic liver disease, cirrhosis and hepatocellular carcinoma may develop after twenty to thirty years in majority of the cases. Co-morbidity with Hepatitis A, Hepatitis B, HIV and chronic alcoholism leads to increased mortality and also affects the treatment schedule. HCV culture in the standard cell lines has always been difficult. Given the fact that the virus undergoes frequent mutations, the precise identification of the genotype has often been questionable. Moreover, a patient may sometimes be infected with more than one genotype at the same time. Because of these above inherent limitations, the availability of reliable diagnostic kits and the development of an effective vaccine as equally the therapy for HCV infection have all been formidable challenges. Despite the various modalities of the virus culture and efforts to develop HCV vaccines using helper adenovirus and baculovirus vectors during the last over two decades, the research in this context has still to go a long journey through as the task is yet unfinished [3-7].

Future Treatment of Hepatitis C: What will be the Fate of Ribavirin?

When I began my career as a hepatologist in 1988 there were no treatments for viral hepatitis. In fact, hepatitis C (HCV), then known as non-A, non-B (NANB) hepatitis, was not discovered until the following year. Almost a decade passed before treatment for HCV became available that resulted in acceptable Sustained Virologic Response (SVR) rates (now known to be consistent with virologic cure) - a combination of Interferon alpha (IFN) plus Ribavirin (RBV). Prior to this pairing, less than 10% of HCV patients achieved a SVR when treated with IFN alone. With combination therapy, SVR rates rose to approximately 40-50%.

Early Results of Left Carotid Chimney Technique in Endovascular Repair of Acute Non-A–Non-B Aortic Dissections

To report our early experience with endovascular repair of acute non-A-non-B aortic dissections using chimney grafts to preserve blood flow to a left common carotid artery (LCCA) located in the proximal landing zone. From June 2009 to May 2010, 8 patients (7 men; mean age 49 years, range 29-75) with acute non-A-non-B aortic dissection and no adequate proximal sealing zones underwent thoracic endovascular aortic repair (TEVAR). Covered stents were placed parallel to the aortic stent-grafts to restore flow to the LCCAs while extending the proximal fixation zones; the left subclavian arteries were intentionally covered after carefully cerebrovascular assessment. Follow-up examinations included computed tomography (CT) at 2 weeks, 3 months, 6 months, 12 months, and yearly thereafter. All the procedures were completed successfully, with one main aortic stent-graft deployed and one chimney graft implanted in the LCCA. Two retrograde type II endoleaks identified intraoperatively were left untreated but followed closely using CT. There were no instances of puncture site complications, stroke, paralysis, or death during the hospital stay. The 30-day mortality was 0%. During the mean 11.4-month follow-up (range 6-15), there was no mortality, and duplex ultrasound and CT showed patency of all stent-grafts, enlargement of the true lumen, and compression of the false lumen. One type II endoleak disappeared in 2 weeks postoperatively, while the other gradually faded until it was nearly gone at 11 months postoperatively. During follow-up, no renal insufficiency, new late endoleaks, endograft migration, fracture, stent-graft related complications, or deaths were observed. In short-term follow-up, TEVAR combined with the chimney technique seems promising for aortic dissections that involve the aortic arch with inadequate proximal sealing zones. More cases and long-term results are needed to evaluate the safety and efficiency of this alternative endovascular technique.

Hepatitis C virus infection and hepatocarcinogenesis

It is evidenced that both HBV and HCV infections may cause chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). HCV is considered as an oncogen virus. The mechanism of carcinogenesis in case of the two distinct viruses shows a number of common and different features. HCC usually develops in stage of liver cirrhosis caused by chronic inflammation of many years or decades. In contrast to HBC, HCV will not be incorporated into the genome of hepatocytes. It induces throughout different mechanisms the development of cancer cells, which will proliferate out of control. Before the discovery of HCV, the connection of non-A non-B (NANB) hepatitis and liver cancer has yet been observed. The subsequent epidemiological studies confirmed this association. A number of publications prove that HCC may develop without cirrhosis in HCV infected patients. The exact mechanism is not known, but data indicate that some proteins of the virus may induce oncogenic process. Differences were found in HCV core gene between HCC patients with and without cirrhosis. It is postulated that the virus evolves its oncogenic effect via endoplasmic and oxidative stress, further on by activation of different oncogenic signal pathways. Recent publications indicate the role of virus induced insulin resistance. Besides the virus determined factors, the host reaction, the deficient tumor cell eliminating capacity may also have a role in the development of liver carcinoma. Monitoring of HCV infected patients for HCC is an important clinical issue. Most relevant is the regular ultrasound cheek up. Serum alpha fetoprotein level is elevated only in a smaller proportion of the patients. The treatment protocol of HCV induced HCC does not differ from the others developed in non-HCV liver diseases.

The history of the “natural history” of hepatitis C (1968–2009)

In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that approximately 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review.

Long-term follow-up of anti-hepatitis C virus antibodies in patients with acute nonA nonB hepatitis and different outcome of liver disease.

We screened 74 patients with nonA nonB acute hepatitis (37 of post-transfusion PTH, and 37 of non-post-transfusion, NPTH, origin) for the presence of anti-HCV by tests detecting either C100-3 antibodies alone (ELISA I) or C100-3 plus C33c plus C22-3 antibodies (ELISA II). Samples were taken at the onset of disease and then serially for a period of time ranging from 12 to 60 months. An increased number of anti-HCV positive cases (86% vs 69%) and an earlier seroconversion were observed with the second compared to the first generation ELISA. Positive samples were confirmed by recombinant immunoblot assay (RIBA), which was also used to study the kinetics of the antibody response to individual HCV antigens. Anti-C33c and anti-C22-3 antibodies were the first detectable markers of HCV infection in 80% and 20% of the patients, respectively. Thirty-two percent of the patients studied showed complete and persistent biochemical recovery, whereas 68% maintained a chronic elevation of the transaminase values. Among the 20 patients who showed early and persistent normalization of the transaminase values, complete disappearance of all antibody reactivities was limited to five of them, whereas in four cases only anti-C100-3 and anti-5-1-1 became negative.

Association of fulminant non‐A non‐B hepatitis with homozygosity for HLA A1‐B8‐DR3

For the majority of cases of acute liver failure in western Europe and North America an etiology cannot be defined. The condition is most often called fulminant non-A, non-B (NANB) hepatitis. Features such as female preponderance and presence of serum autoantibodies suggest a possible autoimmune basis. The aim of the present paper was to examine a possible human leukocyte antigen (HLA) association with fulminant NANB hepatitis. HLA A, B, and DR data of 55 adult Caucasian fulminant NANB patients were compared with those of 1449 local Caucasian controls. In Caucasian patients, homozygosity (but not heterozygosity) for the alleles A1, B8, and DR3 were associated with fulminant NANB hepatitis (Pcorrected = 0.02, <0.00001 and 0.002, respectively). Greatest relative risk (RR) was associated with homozygosity for the A1-B8-DR3 haplotype (P < 0.00001; RR: 12.8; 95% confidence interval [CI]: 5.7-22.3). HLA DR8 was also associated with development of the syndrome (RR: 4.2; 95%CI: 1.6-9.2). Homozygosity for the HLA haplotype A1-B8-DR3 confers susceptibility to the development of fulminant NANB hepatitis. This observation may imply a role for the immune response genes (which are flanked by HLA B and DR) in the pathogenesis of this syndrome.