Treatment of hepatitis C virus infection: Updated Swedish Consensus recommendations

Figures & data

Table I.  Simplified system for histopathological assessment of chronic hepatitis (Hans Glaumann).

	Inflammation grade
Score	Portal inflammation	Interface hepatitis	Lobular inflammation/necrosis	Fibrosis stage
0	None	None	None	None
1	Minimal	Minimal	Only inflammation	Portal fibrosis
2	Mild	Mild	Mild necrosis	Periportal fibrosis
3	Moderate	Moderate	Marked necrosis	Septal fibrosis
4	Severe	Severe	Severe with bridging	Cirrhosis with nodules

Table II.  Sustained virological response (%) after combination therapy with pegylated interferon (peg-IFN) and ribavirin or IFN and ribavirin: results from 2 randomized, controlled 48-week trials.

	Peg-IFN α-2b vs IFN^a		Peg-IFN α-2a vs IFN^b
	Peg-IFN α-2b	IFN α-2b	Peg-IFN α-2a	IFN α-2b
	1.5 µg/kg/week	3×10^6 U 3 times weekly	180 µg/week	3×10^6 U 3 times weekly
	+ ribavirin	+ ribavirin	+ ribavirin	+ ribavirin
	800 mg	1000–1200 mg	1000–1200 mg	1000–1200 mg
	(n =511)	(n =505)	(n =453)	(n =444)
All	54	47	56	44
Genotype 1	42	33	46	36
Genotype 2/3	82	79	76	61
Genotype 4/5/6	50	38	77	36

^aManns et al. Lancet 2001;358:958–65. ^bFried et al. N Engl J Med 2002;347:975–82.

Table III.  Sustained virological response (%) after combination therapy with pegylated interferon α-2a (peg-IFN α-2a) and ribavirin, grouped according to treatment duration and ribavirin dose.

	Peg-IFN α-2a (180 µg/week, 24 weeks)		Peg-IFN α-2a (180 µg/week, 48 weeks)
	Ribavirin 800 mg (n =207)	Ribavirin 1000-1200 mg (n =280)	Ribavirin 800 mg (n =361)	Ribavirin 1000-1200 mg (n =436)
Genotype 1	29	41	40	51
Genotype non-1	78	78	73	77

Modified from Hadziyannis et al. Ann Intern Med 2004;140:346–55.

Table IV.  Recommended treatment doses.

	Genotype 2 or 3
Genotype 1 or 4	12-16 weeks treatment duration	24 weeks treatment duration
Peg-IFN α-2a 180 µg/week and Ribavirin 1000 mg daily if <75 kg and 1200 mg if ≥ 75 kg	Peg-IFN α-2a 180 µg/week	Peg-IFN α-2a 135 µg/week
or	or	or
Peg-IFN α-2b 1.0–1.5^a µg/kg/week, and ribavirin 800 mg daily if 40–64 kg, 1g if 65–85 kg, 1.2 g if 86–105 kg, and 1.4 g if >105 kg	Peg-IFN α-2b 1.5 µg/kg/week in combination with Ribavirin 800 mg daily^b	Ribavirin 800 mg daily^b

^aWhen analysing the total study population, both doses of Peg-IFN α-2b gave similar SVR in the IDEAL study.

^bPost -hoc analysis of several studies indicate that a weight based dosing of ribavirin (≥11 mg/kg body weight daily) may result in improved outcome.

Table V.  Recommended treatment duration.

Virological response	Definition	Genotype 1 or 4	Genotype 2 or 3
vRVR	HCV RNA < 1000 IU/mL d 7		12–16 weeks^a
RVR	HCV RNA undetectable^b week 4	24 weeks	24 weeks
cEVR	HCV RNA undetectable^b week 12	48 weeks	≥24 weeks
pEVR	HCV RNA ≥2 log10 reduction week 12	consider 72 weeks	consider ≥48 weeks

Patients not achieving pEVR or having detectable HCV RNA after 24 weeks of therapy should discontinue treatment.

^aIf dose reductions have been avoided and RVR is also achieved. ^bLimit of detection of HCV RNA analysis ≤15 IU/ml.

Table VI.  Recommended start doses for ribavirin in patients with renal impairment according to creatinine clearance in a patient weighing 70 kg.

Creatinine clearance (ml/min)	80	60	40	20
Ribavirin start dose (mg/d)	800	600	400	400 three times weekly

Modified from Bruchfeld et al. Therapeutic Drug Monitoring 2002;24:701–8.

Table VII.  Contraindication to combination therapy with peg-IFN and ribavirin.

Absolute contraindications	Pregnancy^a, decompensated cirrhosis (interferon), autoimmune hepatitis (interferon), solid organ transplant excluding liver (interferon), severe anaemia (ribavirin), hypersensitivity to interferon or ribavirin, children below 3 y of age (peg-IFN α-2a due to bensylalcohol additive).
Relative contraindications	Depression or over-serious psychiatric disorder, seizures, cardiac disdease, anaemia (<100 g/l), neutropenia (<0.75×10^9/l), thrombocytopenia (<50×109/l), haemoglobinopathy (ribavirin), renal impairment (see text), suboptimally treated thyroid disease, suboptimally treated diabetes mellitus, other automimmune disease, psoriasis, sarcoidosis, ongoing or recent illicit drug use.

^aContraception for all patients is important through therapy, and 4 months after for female patients and their partners; and 7 months after for male patients because of the teratogenic effect of ribavirin.

Table VIII.  Basic monitoring during combination therapy.

HCV RNA quantification	D 7 (i.e. just prior to 2nd dose of peg-IFN for genotypes 2/3), weeks 4, 12, 24, end of treatment, and 2 independent samples ≥6 months after discontinuation of therapy.
Physical examination (including weight)	Every third month
Haemoglobin, WBC neutrophil count, platelet count	Weeks 1, 2, 4, and thereafter at least every 4th week
ALT, serum bilirubin	Every 4th week
TSH, thyroxin	Every 3rd month and 6 months after discontinuation of therapy