Thomas Göbel

Response to antiviral treatment in patients infected with hepatitis B virus genotypes E–H

No data on antiviral response of HBV genotypes E–H are available so far although these HBV genotypes contribute significantly to the global HBV burden. Of 49 patients with HBV genotypes E–H, 23 received interferon (IFN)‐alpha, 12 nucleos(t)ide analogues and 14 patients were untreated. HBV genotype was determined by direct sequencing of the HBV S gene. Sustained virological response in IFN‐treated patients was defined as normalization of ALT and decrease of HBV‐DNA <4,000 IU/ml 6 months after treatment. Virological response with nucleos(t)ide analogues was assumed in patients with a HBV‐DNA <200 IU/ml after 48 weeks of treatment. HBV genotype E was found in 61.2% (n = 30), HBV genotype F in 8.2% (n = 4), HBV genotype H in 10.2% (n = 5) of patients. Among patients with HBV genotype G (20.4%; n = 10) there were four HBV genotype G/A and three HBV genotype G/C co‐infections. Patients had Caucasian (43%), African (55%), or Asian (2%) background. End of treatment response was 70% (16/23) and sustained virological response was 35% (8/23) for patients treated with IFN‐alpha. Sustained virological response was 36% for HBV genotype E (n = 5/14), 50% for HBV genotype F or H (n = 2/4), and 20% for HBV genotype G (n = 1/5). Virus suppression at week 48 was achieved in 67% of patients treated with nucleos(t)ide analogues. According to the present preliminary data HBV genotypes E, F, and H appear to be sensitive to IFN‐alpha. Lower rates of response to IFN‐alpha in patients with HBV genotype G might be related to the frequent occurrence of double infection. J. Med. Virol. 81:1716–1720, 2009.

High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe

The indication for antiviral treatment of patients with chronic hepatitis B is based on serum HBV DNA levels, transaminases, and histological grade and stage. The relation of liver fibrosis and inflammation to ALT activity in chronic hepatitis B infection was investigated in a non‐endemic, European setting. A total of 253 patients with chronic hepatitis B who had undergone liver biopsy at the Clinic of Gastroenterology, Hepatology, and Infectious Diseases, Düsseldorf, Germany over the past 19 years (1990–2009) were evaluated. Thirty‐nine patients had persistently normal transaminases, 86 patients had ALT with 1–2 × ULN (upper limit of normal) and 128 patients had ALT >2 × ULN. Liver fibrosis or inflammation was defined as significant for stages or grades ≥ 2 according to the Desmet/Scheuer score. Significant liver fibrosis (F ≥ 2) was found in 36%, cirrhosis in 18%, and significant inflammation (G ≥ 2) in 27% of patients with normal transaminases. There was no difference in the stage of liver fibrosis and the frequency of cirrhosis between patients with normal and elevated transaminases. The most important factor associated with the presence of cirrhosis in multivariate analysis was age ≥40 years (P < 0.003). If concomitant factors like elevated GGT or male sex were furthermore present high prevalences of significant liver disease were found. The data indicate that, in a European setting, patients with chronic hepatitis B infection, and normal transaminases frequently have significant liver fibrosis or cirrhosis. Therefore, liver biopsy or liver stiffness measurement (LSM) should be performed in these patients to determine the stage of liver fibrosis. J. Med. Virol. 83:968–973, 2011.

Retrospective Analysis of Chronic Hepatitis D in a West German University Clinic over Two Decades: Migratory Pattern, Prevalence and Clinical Outcome

BACKGROUND/AIMS Epidemiology, clinical features and long term-course of chronic hepatitis D were addressed in a non-endemic Central European area. METHODS Sixty-seven patients with chronic hepatitis D were identified among 1307 HBsAg carriers at the university hospital Düsseldorf during two decades (1989 - 2008) and followed for a mean of 7 +/- 6 years. Forty-one of these were treated with IFN-alfa for at least six months. RESULTS Hepatitis D prevalence increased from 4.1 to 6.2 % among HBsAg carriers during the two decades (p < 0.06). Patients originating from the former Soviet Union (32.1 vs. 46.2 %) and Africa (0 vs. 17.9 %) became more frequent whereas the prevalence of patients from Southern Europe declined (46.5 vs.17.9 % p < 0.03). The time span between the diagnosis of hepatitis B and D was 4.8 +/- 7 years (p < 0.0001). A sustained virological response to interferon-alfa was achieved in 19.5 % of the patients. The yearly incidence rates for death, HCC and complications were 3.2 %, 2.7 % and 8 % among patients with liver cirrhosis. Estimated survival and complication-free survival during 12 years were 72 % and 45 % in cirrhotic compared to 100 % in non-cirrhotic patients (p < 0.008 and p < 0.0001, respectively). CONCLUSION Hepatitis D in western Germany appears to be on the increase and has a migration background that should be considered in clinical practice. Clinical outcome and response to IFN are as poor as in endemic regions, indicating the need to improve early diagnosis.

Transient elastography improves detection of liver cirrhosis compared to routine screening tests

AIM To investigate the diagnostic significance of transient elastography (TE) in a daily routine clinical setting in comparison to clinical signs, laboratory parameters and ultrasound. METHODS TE, ultrasound, laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine. RESULTS Sensitivity of TE for the detection of liver cirrhosis was 90.4%, compared to 80.1% for ultrasound, 58.0% for platelet count and 45.1% for cutaneous liver signs (P < 0.0001 for comparisons with histology). AUROC for TE was 0.760 (95%CI: 0.694-0.825). Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825 (95%CI: 0.768-0.882). TE correlated with laboratory parameters of cirrhosis progression like albumin (r = -0.43), prothrombin time (r = -0.44), and bilirubin (r = 0.34; P < 0.001 for each). Particularly, in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1% (P < 0.04) and 16.3% (P < 0.02), respectively. CONCLUSION Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

A returning traveller with fever, facial swelling, and skin lesions

A 58 year old man presented to the emergency department with fevers and lethargy. He had recently been in Zambia for 15 days, where he had spent time in Lusaka and at a game reserve. Three days earlier, while still in Lusaka, he had noted painful swellings on his right leg and fever, and although a malaria test was negative the fevers continued, so he returned home to Germany early. At presentation, he was drowsy and his speech was slurred, so the history was obtained from his sister. He had not taken antimalarials during his trip, but he had been vaccinated against tetanus, diphtheria, and rabies before travel. On examination his temperature was 39.4°C, respiration 18 breaths/min, pulse 96 beats/min, and blood pressure 95/80 mm Hg. His Glasgow coma score was 12/15, and facial swelling was noted around his eyes and cheeks. Apart from moderate hepatosplenomegaly and a systolic mitral valve click owing to a St Jude prosthesis implanted five years earlier, his physical examination was normal. There was no focal neurological abnormality or evidence of meningism. A generalised macular exanthema was noted on his trunk, along with two indurated skin lesions about 6 cm in diameter on his right leg (fig 1⇓). Blood tests showed haemoglobin 126 g/L (normal range 140-180), leucocytes 5.6×109 cells/L (4-11; lymphocytes 0.02 (0.25-0.4.), neutrophils 0.84 (0.50-0.75)), platelets 40×109 cells/L (150-400), C reactive protein 1807 μmol/L (8-31), creatine kinase 364 U/L (<171), total bilirubin 51.85 μmol/L (<17.0), aspartate aminotransferase 163 U/L (<35), alanine aminotransferase 205 U/L (<45), γ-glutamyltransferase 274 (<55) U/L, serum creatinine 477.36 μmol/L (<97). Serum electrolytes were within the normal range. Urine dipstick was positive for protein, erythrocytes, and leucocytes as well as some hyaline casts. Blood films were negative for malaria but showed unusual extracellular structures (fig 2 …

Chronic hepatitis B with an unexpected co-infection.

BACKGROUND Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected. CASE REPORT A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment. RESULTS Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started. CONCLUSION Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.ZusammenfassungHintergrund:Weltweit sind 350 Millionen Menschen mit dem Hepatitis- B-Virus (HV) infiziert, insbesondere in tropischen Regionen. Die Schistosomiasis (Bilharziose) ist eine Tropenerkrankung mit 200 Millionen Infizierten, sodass eine hohe Rate an Koinfektonen zu erwarten ist.Fallbeschreibung:Ein 34-jähriger, afrikanischer Patient wurde mit einer bekannten Hepatitis B/D-Koinfektion zur Beurteilung einer antiviralen Therapie in unsere Klinik überwiesen.Ergebnisse:Überraschenderweise zeigte sich neben den viral induzierten Veränderungen innerhalb der Leberbiopsie ein Granulom mit einem Schistosomen- Ei. In den hierauf veranlassten Stuhluntersuchungen konnte der Parasit als Schistosoma mansoni identifiziert werden. Vor Einleitung einer anti viralen Therapie wurde eine antischistosomale Therapie mit Praziquantel durchgeführt.Schlussfolgerung:Patienten, die aus tropischen Ländern stammen und an einer chronisch viralen Hepatitis leiden, können weitere Koinfektionen aufweisen, die in der täglichen klinischen Routine leicht übersehen werden. Bei Patienten aus Bilharziose-Endemiegebieten und begründetem Verdacht auf eine parasitäre Koinfektion sollte eine tropenmedizinische Abklärung erfolgen.AbstractBackground:Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected.Case Report:A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment.Results:Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started.Conclusion:Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.

Chronische Hepatitis B mit einer unerwarteten Koinfektion

BACKGROUND Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected. CASE REPORT A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment. RESULTS Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started. CONCLUSION Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.ZusammenfassungHintergrund:Weltweit sind 350 Millionen Menschen mit dem Hepatitis- B-Virus (HV) infiziert, insbesondere in tropischen Regionen. Die Schistosomiasis (Bilharziose) ist eine Tropenerkrankung mit 200 Millionen Infizierten, sodass eine hohe Rate an Koinfektonen zu erwarten ist.Fallbeschreibung:Ein 34-jähriger, afrikanischer Patient wurde mit einer bekannten Hepatitis B/D-Koinfektion zur Beurteilung einer antiviralen Therapie in unsere Klinik überwiesen.Ergebnisse:Überraschenderweise zeigte sich neben den viral induzierten Veränderungen innerhalb der Leberbiopsie ein Granulom mit einem Schistosomen- Ei. In den hierauf veranlassten Stuhluntersuchungen konnte der Parasit als Schistosoma mansoni identifiziert werden. Vor Einleitung einer anti viralen Therapie wurde eine antischistosomale Therapie mit Praziquantel durchgeführt.Schlussfolgerung:Patienten, die aus tropischen Ländern stammen und an einer chronisch viralen Hepatitis leiden, können weitere Koinfektionen aufweisen, die in der täglichen klinischen Routine leicht übersehen werden. Bei Patienten aus Bilharziose-Endemiegebieten und begründetem Verdacht auf eine parasitäre Koinfektion sollte eine tropenmedizinische Abklärung erfolgen.AbstractBackground:Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected.Case Report:A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment.Results:Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started.Conclusion:Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.

Chronische Hepatitis B mit einer unerwarteten Koinfektion@@@Chronic Hepatitis B with an Unexpected Coinfection

BACKGROUND Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected. CASE REPORT A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment. RESULTS Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started. CONCLUSION Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.ZusammenfassungHintergrund:Weltweit sind 350 Millionen Menschen mit dem Hepatitis- B-Virus (HV) infiziert, insbesondere in tropischen Regionen. Die Schistosomiasis (Bilharziose) ist eine Tropenerkrankung mit 200 Millionen Infizierten, sodass eine hohe Rate an Koinfektonen zu erwarten ist.Fallbeschreibung:Ein 34-jähriger, afrikanischer Patient wurde mit einer bekannten Hepatitis B/D-Koinfektion zur Beurteilung einer antiviralen Therapie in unsere Klinik überwiesen.Ergebnisse:Überraschenderweise zeigte sich neben den viral induzierten Veränderungen innerhalb der Leberbiopsie ein Granulom mit einem Schistosomen- Ei. In den hierauf veranlassten Stuhluntersuchungen konnte der Parasit als Schistosoma mansoni identifiziert werden. Vor Einleitung einer anti viralen Therapie wurde eine antischistosomale Therapie mit Praziquantel durchgeführt.Schlussfolgerung:Patienten, die aus tropischen Ländern stammen und an einer chronisch viralen Hepatitis leiden, können weitere Koinfektionen aufweisen, die in der täglichen klinischen Routine leicht übersehen werden. Bei Patienten aus Bilharziose-Endemiegebieten und begründetem Verdacht auf eine parasitäre Koinfektion sollte eine tropenmedizinische Abklärung erfolgen.AbstractBackground:Schistosomiasis and hepatitis B are both tropical diseases with more than 200 and 350 million people infected worldwide respectively, but are rare in western countries. Worldwide a high rate of coinfections can be expected.Case Report:A 34-year-old African patient was referred to our clinic with known hepatitis B/D-coinfection for evaluation of antiviral treatment.Results:Surprisingly, liver biopsy showed a granuloma with the egg of Schistosoma in addition to virus induced alterations. Subsequent examination of the stool allowed to classify the parasite as Schistosoma mansoni. Thus, before initiation of an antiviral treatment, an antischistosomal therapy with praziquantel leading to elimination of schistosomiasis was started.Conclusion:Patients from tropical countries suffering from chronic viral hepatitis may present with additional coinfections which can be earily overlooked in daily clinical routine. Screening of African patients from endemic areas for schistosomiasis should include examinations for tropical diseases by specialists.