N ephron 1992:61:255-257
Clinic of Infectious Diseases, University of Ancona, Italy
Viral Hepatitis: Modern Aspects of Clinical Diagnosis
Key W ords
A bstract
Hepatitis Viral Parenteral
In these years, more light has been brought into the field of hepatitis viruses, particularly with regard to their biology and etiopathogenesis. Besides, first attempts of specific therapy have been done, thanks to the introduction of interferons. This paper wants to give the main guidelines of up-to-date diagnosis and treatment of hepatitis supported by viral infection.
Involvement of hepatic parenchyma by viral agents may be primitive or secondary in the course of general disease (table I). Among viruses with the liver as primary localiza tion, there must not be forgotten non-A, non-B viruses (which, even after the C virus discovery, represent 20% of post-transfusional and 30-50% of sporadic hepatitis) [ I] and the E type virus, partially characterized at present, but known to be responsible for frequent epidemics in Asia and Africa [2], Besides, it must be underlined that relating to the parenteral mechanism of transmission, we have to consider even the «appearently non-parenteral» transmission, which happens among cohabitants with infected patients, as a part of the same mechanism. Clinical evolution of viral hepatitis can be different, according to the viruses involved (table 2). Once the chronicity condition of hepatitis sup ported by B or C virus infection is established, the probabili ty of cirrhotic evolution is considered to be about 20% for both viruses. Differently evaluated is the role of each virus in causing transition cirrhosis-carcinoma of the liver: while in Africa 80% of liver carcinomas are ascribed to B virus infection, in Japan 40% seem to be related to the C type [3]. The importance to be given to the prevention of post-trans fusional hepatitis by seric antibody screening, first of all of those related to the C virus, is then well understandable, showing this to be a shifty clinical course and a frequent evolution towards cirrhosis. Up to now, thanks to B and C
Table 1. Viral hepatitis - viruses Type
Virus
Primary localization
A B C Delta E Non-A, non-B
HAV HBV HCV HDV HEV 9
Secondary localization
EBV CMV Herpes simplex Mumps Others
virus screening techniques, the total incidence of post-tranfusional hepatitis has been reduced to 2-3% of blood trans fusions [4], With regard to the delta virus, it is worth noting the different seriousness of delta-B coinfection, if com pared with superinfection of an asymptomatic B virus car rier (5% of chronicizations in the former condition, versus 70% in the latter). Considering now diagnostic possibilities (table 3), we tried to summarize what the laboratory can
Prof. Giorgio Scalisc Clinic of Infectious Diseases Ospcdalc Umberto I . Largo Cappclli I I 60121 Ancona (Italy)
© 1992 S. Karger AG, Basel (K)28-2766/92/ 06I3-Ö255S2.75/0
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
Giorgio Scalise Giovanni Corbelli
Table 2.
Evolution of B and non-A, non-B hepatitis
Non-A, non-B
HBV
25-50% 90% Recovery " *"
1 Chronicity 50-70% 1 Chronically active 40% 1 Cirrhosis 20%
1 Chronicity 6-10% 1 i Chronically active 50% l Cirrhosis 25%
Risk of liver carcinoma
Table 3.
Hepatitis viruses-viral markers
Infection
Replication
Immunity
HAV HAV (stool)
IgM anti-HAV
IgG anti-HAV
HBV HBsAg anti-HBc anti-HBe
HBV-DNA HBeAg IgM anti-HBc
anti-HBs anti-HBc
HCV anti-HCV
HCV-RNA (liver) IgG anti-HCV IgM anti-HCV
HDV anti-HDV (1/100.000) HDV-RNA HDAg IgM anti-HD anti-HEV HEAg (liver)
HEV none
Table 4.
anti-HDV (1/100,000)
offer in this field [5], Generally, a fundamental distinction must be operated between acute infection and active viral replication on a side, and immunity condition, clinically silent, on the other. Generally, IgM class antibodies are good indicators of hepatitis virus replication. Specific ther apy of chronic hepatitis (as of persistent and of active type); are nowadays guaranteed by the clinical use of interferons (first of all a type; table 4) [6-8]. This, after initial experi ences, suggested to employ dosages higher than those previ ously forecasted (6-18 MU in 3 administrations per week, versus initial 3 MU), and to lengthen the treatment period up to 2 years, even if with decreasing dosages. This in order to increase probabilities of success, with regard to the percentage of responses to a 1-year therapy and to the reduction of re-emerging hepatitic process once interferon administration has been interrupted. However, scientists still recognize a limited role to interferon therapy because of side effects, preventing in 10-20% of cases instigation of therapy. Besides, it is even possible to decrease the thera peutic result, owing to specific antibody formation, or to a lack in suitable cellular receptors. We underline here the high value still represented by prophylactic measures against chronically active hepatitis and carcinoma of the liver. Effective and safe vaccine and immunoglobulins against B virus infection are today the only suitable mea sures. Not as much may be said for C type virus, the prevention of which must be committed to more general screening and protection rules, thus representing one of the most up-to-date challenges for medicine.
none
Type B and C chronic hepatitis - therapy with interferon
Indications
Infections with viral replication and histologic alterations Purposes
Control of viral replication and disappearance of HBV-DNA and HBeAg from serum and of HBcAg or HCV-DNA from the liver Prevention of viral integration (disappearance of HBeAg and seroconversion to HBsAb) Serum transaminase normalization Histologic resolution of hepatic necrosis Contraindications
256
Scallse/Corbelli
Viral Hepatitis
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
Serious cardiac or renal diseases Decompensating hepatic cirrhosis
References 5
6
Van Der Poel CL, Cuypers HTM. Reesink HW, Weiner AJ, Quan S, di Nello R, Van Boven JJP, Winkel I. Mulder-Folkerts D, Exel-Oelers PJ, Schaasberg W, Leentvar-Kuypers A. Polito A, Hougton M, Lelie PN: Confirmation of hepati tis C virus infection by new four-antigen recom binant immunoblot essay. Lancet 1990:335:1-3. Alexander GJM, Brahm J, Fagan EA, Smith HM, Daniels HM, Eddieston ALWF, Williams R: Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987:0:66-68.
7
8
Brook MG, Chan G, Yap I, Karayiannis P, Lever AML, Jacyna M. Main J. Thomas HC: Randomized controlled trial of limphoblastoid interferon alpha in European men with chronic hepatitis B virus infection. Br Med J 1989; 299:652-656. Saracco G, Mazzella G: A controlled trial of human lymphoblastoid interferon in chronic hepatits B in Italy. Hepatology 1989:10:336-341.
257
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
1 Weiner AJ. Kuo G. Bradley DW, Bonino F, Saracco G. Lee C, Rosenblatt J, Choo Q. Hougton M : Detection of hepatitis C viral sequences in non-A, non- B hepatitis. Lancet 1990:335:1-3. 2 Zuckermann AJ: Hepatitis E virus. Br Med J 1990:300:1475-1476. 3 Nishioka K: Hepatitis C virus antibody and hepatocellular carcinoma. Update 1990;4:2-3. 4 Mosley JW. Aach RD, Hollinger FB, Stevens CE, Barbosa LH. Nemo GJ, Holland PV, Ban croft WM, Zimmermann HG, Kuo G, Choo Q. Hougton M: Non A. non B hepatitis and anti body to hepatitis C virus. JAMA 1990; 263:77-78.
Clinic of Infectious Diseases, University of Ancona, Italy
Viral Hepatitis: Modern Aspects of Clinical Diagnosis
Key W ords
A bstract
Hepatitis Viral Parenteral
In these years, more light has been brought into the field of hepatitis viruses, particularly with regard to their biology and etiopathogenesis. Besides, first attempts of specific therapy have been done, thanks to the introduction of interferons. This paper wants to give the main guidelines of up-to-date diagnosis and treatment of hepatitis supported by viral infection.
Involvement of hepatic parenchyma by viral agents may be primitive or secondary in the course of general disease (table I). Among viruses with the liver as primary localiza tion, there must not be forgotten non-A, non-B viruses (which, even after the C virus discovery, represent 20% of post-transfusional and 30-50% of sporadic hepatitis) [ I] and the E type virus, partially characterized at present, but known to be responsible for frequent epidemics in Asia and Africa [2], Besides, it must be underlined that relating to the parenteral mechanism of transmission, we have to consider even the «appearently non-parenteral» transmission, which happens among cohabitants with infected patients, as a part of the same mechanism. Clinical evolution of viral hepatitis can be different, according to the viruses involved (table 2). Once the chronicity condition of hepatitis sup ported by B or C virus infection is established, the probabili ty of cirrhotic evolution is considered to be about 20% for both viruses. Differently evaluated is the role of each virus in causing transition cirrhosis-carcinoma of the liver: while in Africa 80% of liver carcinomas are ascribed to B virus infection, in Japan 40% seem to be related to the C type [3]. The importance to be given to the prevention of post-trans fusional hepatitis by seric antibody screening, first of all of those related to the C virus, is then well understandable, showing this to be a shifty clinical course and a frequent evolution towards cirrhosis. Up to now, thanks to B and C
Table 1. Viral hepatitis - viruses Type
Virus
Primary localization
A B C Delta E Non-A, non-B
HAV HBV HCV HDV HEV 9
Secondary localization
EBV CMV Herpes simplex Mumps Others
virus screening techniques, the total incidence of post-tranfusional hepatitis has been reduced to 2-3% of blood trans fusions [4], With regard to the delta virus, it is worth noting the different seriousness of delta-B coinfection, if com pared with superinfection of an asymptomatic B virus car rier (5% of chronicizations in the former condition, versus 70% in the latter). Considering now diagnostic possibilities (table 3), we tried to summarize what the laboratory can
Prof. Giorgio Scalisc Clinic of Infectious Diseases Ospcdalc Umberto I . Largo Cappclli I I 60121 Ancona (Italy)
© 1992 S. Karger AG, Basel (K)28-2766/92/ 06I3-Ö255S2.75/0
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
Giorgio Scalise Giovanni Corbelli
Table 2.
Evolution of B and non-A, non-B hepatitis
Non-A, non-B
HBV
25-50% 90% Recovery " *"
1 Chronicity 50-70% 1 Chronically active 40% 1 Cirrhosis 20%
1 Chronicity 6-10% 1 i Chronically active 50% l Cirrhosis 25%
Risk of liver carcinoma
Table 3.
Hepatitis viruses-viral markers
Infection
Replication
Immunity
HAV HAV (stool)
IgM anti-HAV
IgG anti-HAV
HBV HBsAg anti-HBc anti-HBe
HBV-DNA HBeAg IgM anti-HBc
anti-HBs anti-HBc
HCV anti-HCV
HCV-RNA (liver) IgG anti-HCV IgM anti-HCV
HDV anti-HDV (1/100.000) HDV-RNA HDAg IgM anti-HD anti-HEV HEAg (liver)
HEV none
Table 4.
anti-HDV (1/100,000)
offer in this field [5], Generally, a fundamental distinction must be operated between acute infection and active viral replication on a side, and immunity condition, clinically silent, on the other. Generally, IgM class antibodies are good indicators of hepatitis virus replication. Specific ther apy of chronic hepatitis (as of persistent and of active type); are nowadays guaranteed by the clinical use of interferons (first of all a type; table 4) [6-8]. This, after initial experi ences, suggested to employ dosages higher than those previ ously forecasted (6-18 MU in 3 administrations per week, versus initial 3 MU), and to lengthen the treatment period up to 2 years, even if with decreasing dosages. This in order to increase probabilities of success, with regard to the percentage of responses to a 1-year therapy and to the reduction of re-emerging hepatitic process once interferon administration has been interrupted. However, scientists still recognize a limited role to interferon therapy because of side effects, preventing in 10-20% of cases instigation of therapy. Besides, it is even possible to decrease the thera peutic result, owing to specific antibody formation, or to a lack in suitable cellular receptors. We underline here the high value still represented by prophylactic measures against chronically active hepatitis and carcinoma of the liver. Effective and safe vaccine and immunoglobulins against B virus infection are today the only suitable mea sures. Not as much may be said for C type virus, the prevention of which must be committed to more general screening and protection rules, thus representing one of the most up-to-date challenges for medicine.
none
Type B and C chronic hepatitis - therapy with interferon
Indications
Infections with viral replication and histologic alterations Purposes
Control of viral replication and disappearance of HBV-DNA and HBeAg from serum and of HBcAg or HCV-DNA from the liver Prevention of viral integration (disappearance of HBeAg and seroconversion to HBsAb) Serum transaminase normalization Histologic resolution of hepatic necrosis Contraindications
256
Scallse/Corbelli
Viral Hepatitis
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
Serious cardiac or renal diseases Decompensating hepatic cirrhosis
References 5
6
Van Der Poel CL, Cuypers HTM. Reesink HW, Weiner AJ, Quan S, di Nello R, Van Boven JJP, Winkel I. Mulder-Folkerts D, Exel-Oelers PJ, Schaasberg W, Leentvar-Kuypers A. Polito A, Hougton M, Lelie PN: Confirmation of hepati tis C virus infection by new four-antigen recom binant immunoblot essay. Lancet 1990:335:1-3. Alexander GJM, Brahm J, Fagan EA, Smith HM, Daniels HM, Eddieston ALWF, Williams R: Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987:0:66-68.
7
8
Brook MG, Chan G, Yap I, Karayiannis P, Lever AML, Jacyna M. Main J. Thomas HC: Randomized controlled trial of limphoblastoid interferon alpha in European men with chronic hepatitis B virus infection. Br Med J 1989; 299:652-656. Saracco G, Mazzella G: A controlled trial of human lymphoblastoid interferon in chronic hepatits B in Italy. Hepatology 1989:10:336-341.
257
Downloaded by: Kings's College London 137.73.144.138 - 11/11/2017 5:20:46 PM
1 Weiner AJ. Kuo G. Bradley DW, Bonino F, Saracco G. Lee C, Rosenblatt J, Choo Q. Hougton M : Detection of hepatitis C viral sequences in non-A, non- B hepatitis. Lancet 1990:335:1-3. 2 Zuckermann AJ: Hepatitis E virus. Br Med J 1990:300:1475-1476. 3 Nishioka K: Hepatitis C virus antibody and hepatocellular carcinoma. Update 1990;4:2-3. 4 Mosley JW. Aach RD, Hollinger FB, Stevens CE, Barbosa LH. Nemo GJ, Holland PV, Ban croft WM, Zimmermann HG, Kuo G, Choo Q. Hougton M: Non A. non B hepatitis and anti body to hepatitis C virus. JAMA 1990; 263:77-78.
